Sophic Logo gordian knotLung Cancer Clinical Trials Intelligence

Monthly Update Report - October 2025


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Important Notice:
Sophic does not practice medicine nor provide medical advice. The Sophic Starlight Cancer Clinical Trials Intelligence Report is intended solely as an educational resource that provides access to publicly available clinical trial data integrated within Sophic’s proprietary knowledgebase and summarized with AI. This report is not a substitute for professional medical advice, diagnosis, or treatment.

1: Summary data from new trials identified for Lung Cancer.


Overview

Number of Trials: 24

These 24 trials span advanced solid tumors, predominantly lung cancers (NSCLC, SCLC) and other malignancies. Most evaluate novel antibody-drug conjugates (ADCs), immune checkpoint inhibitors, bispecific antibodies, radioligand therapies, and CAR T-cell therapies. Several trials combine immunotherapy with chemotherapy or targeted agents. A subset explores adaptive radiotherapy, fasting-mimicking diets, and screening campaigns. Trials target biomarkers including HER2, HER3, DLL3, PD-L1, KRAS G12C, Nectin-4, IL13Rα2, and MUC-1. Many enroll patients with relapsed/refractory disease after standard therapy.

Common Criteria Across Trials

Common Inclusion

  • Age ≥18 years
  • Histologically or cytologically confirmed advanced or metastatic solid tumor
  • ECOG performance status 0–2
  • Measurable disease per RECIST v1.1
  • Adequate organ function (bone marrow, liver, kidney)
  • Life expectancy ≥3–6 months
  • Prior standard therapy failure or ineligibility
  • Effective contraception required

Common Exclusion

  • Active or uncontrolled infection
  • Active autoimmune disease requiring systemic treatment
  • History of interstitial lung disease or pneumonitis
  • Symptomatic or untreated brain metastases
  • Significant cardiovascular disease (NYHA Class ≥II, recent MI)
  • QTc prolongation >470–480 ms
  • HIV, hepatitis B/C with active replication
  • Prior organ or stem cell transplant
  • Pregnancy or breastfeeding
  • Recent systemic therapy or radiotherapy within specified washout

Outcomes Summary

Primary Outcomes

Secondary Outcomes


2: Extracted Trials with New Information


Trials with Special Criteria

Genomic / Biomarker Trials

Unique or Unusual Criteria

Trials with Emerging Treatments


3: Individual Trial Overviews


NCT06899126

A Phase 3, Multicenter, Randomized, Open-label Trial of Trastuzumab Deruxtecan in Combination With Pembrolizumab Versus Platinum-based Chemotherapy in Combination With Pembrolizumab, as First-line Therapy in Participants With Locally Advanced Unresectable or Metastatic HER2 Overexpressing and PD-L1 TPS <50% Non-squamous Non-small Cell Lung Cancer (DESTINY-Lung06) Genomic-based

Organization/Sponsor: Daiichi Sankyo


Example patient: A 62-year-old adult with newly diagnosed Stage IV non-squamous metastatic NSCLC with HER2 overexpression, PD-L1 TPS 30%, no actionable genomic alterations, no HER2 mutations, adequate pulmonary function, and no history of cardiac disease or interstitial lung disease.

Phase 3

Interventions

  • Drug: Chemotherapy
    Summary: Synthetic or naturally-occurring chemicals used for disease treatment (NCI Thesaurus).
  • Drug: Pemetrexed
    Summary: A folate analog metabolic inhibitor that blocks thymidylate synthase and other enzymes involved in nucleotide synthesis, disrupting DNA synthesis in cancer cells; FDA-approved for non-squamous NSCLC and malignant pleural mesothelioma (FDA label, NCI Thesaurus).
  • Biological: Pembrolizumab
    Summary: A humanized IgG4 monoclonal antibody that blocks PD-1 receptor on T cells, preventing ligand binding and enhancing immune-mediated tumor destruction; FDA-approved for multiple cancers including NSCLC (FDA label, NCI Thesaurus).
  • Biological: Trastuzumab Deruxtecan
    Summary: An antibody-drug conjugate combining HER2-directed monoclonal antibody with a topoisomerase inhibitor payload via cleavable linker, delivering cytotoxic agent directly to HER2-expressing tumor cells; FDA-approved for HER2-positive/low breast cancer, HER2-mutant NSCLC, and other HER2-positive solid tumors (FDA label).

Key Inclusion

  • Adults ≥18 years of age
  • Histologically documented non-squamous locally advanced unresectable or metastatic NSCLC
  • Stage IV or Stage IIIB/IIIC disease not candidate for surgical resection or definitive chemoradiation
  • No known actionable genomic alterations with locally available targeted therapies
  • No known HER2 mutation
  • No prior systemic anticancer therapy for advanced/metastatic non-squamous NSCLC
  • Adequate tumor tissue sample available for HER2 and PD-L1 expression assessment
  • HER2 overexpressing and PD-L1 TPS <50%

Key Exclusion

  • Medical history of myocardial infarction within 6 months or symptomatic CHF (NYHA Class II-IV)
  • QTc prolongation >480 ms
  • History of interstitial lung disease/pneumonitis requiring steroids or current ILD/pneumonitis
  • Lung-specific intercurrent clinically significant illnesses (pulmonary emboli within 3 months, severe asthma, severe COPD, restrictive lung disease, pleural effusion)
  • Prior complete pneumonectomy
  • Prior treatment with topoisomerase I-targeting ADC or HER2-targeted antibody therapy

NCT06956690

A First-in-Human, Open-label, Phase 1/2 Clinical Trial to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of HMBD-501 in Patients With Advanced-Stage, Relapsed/Refractory HER3-Expressing Solid Tumors Genomic-based

Organization/Sponsor: Hummingbird Bioscience


Example patient: A 58-year-old woman with metastatic EGFR-mutated NSCLC expressing HER3, ECOG PS 1, who progressed on osimertinib and platinum-based chemotherapy, weighing 62 kg with no history of pneumonitis.

Phase 1, Phase 2

Interventions

  • Drug: ENV-501
    Summary: ENV-501 is a HER3-targeted antibody-drug conjugate that binds HER3 on tumor cells and delivers exatecan, a DNA topoisomerase I inhibitor, via a hydrophilic cleavable linker to induce DNA damage, cell cycle arrest, and apoptosis in HER3-overexpressing tumors (NCI Thesaurus).

Key Inclusion

  • Body weight ≥40 kg
  • Histologically or cytologically confirmed advanced-stage or metastatic HER3+ solid tumors
  • Relapsed or refractory to or ineligible for standard therapy
  • Unresectable or metastatic cutaneous melanoma (HER3+)
  • Locally advanced or metastatic mutated EGFR NSCLC (HER3+)
  • Unresectable, locally advanced or metastatic breast cancer
  • ECOG performance status 0-2
  • Willingness to undergo fresh tumor biopsy if HER3+ status not documented

Key Exclusion

  • Prior treatment with HER3-targeted ADC or exatecan-conjugated ADC as last line
  • Prior topoisomerase I inhibitor as last line of therapy
  • History of noninfectious or drug-induced pneumonitis or interstitial lung disease
  • Active and uncontrolled infections requiring IV antibiotics within 2 weeks
  • Leptomeningeal disease or symptomatic/uncontrolled brain metastasis
  • Pregnant or positive β-HCG test
  • Active second malignancies requiring therapy
  • Major surgery, radiation therapy, or anti-tumor drug therapy within specified timeframes

NCT07192900

Fast TILs to Treat Metastatic Cancer Patients With Pleural Disease: A Phase I Trial

Organization/Sponsor: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)


Example patient: A 62-year-old patient with mesothelioma and recurrent malignant pleural effusions, Karnofsky score 80, who has failed multiple lines of chemotherapy and has adequate cardiac and organ function without active infections.

Phase 1

Interventions

  • Biological: Interleukin-2
    Summary: Recombinant interleukin-2 that activates T cells and enhances lymphocyte proliferation to induce tumor regression; used to support adoptive cell therapy by promoting T cell expansion and survival (NCI Thesaurus, FDA label).
  • Biological: locally manufactured adoptive cellular therapy (ACT) product
    Summary: Autologous or allogeneic tumor-infiltrating lymphocytes expanded from pleural effusions for immunotherapeutic treatment of metastatic cancer with pleural involvement (NCI Thesaurus).

Key Inclusion

  • Symptomatic biopsy-proven malignant pleural disease or mesothelioma with pleural effusions
  • Refractory to or exhausted available standard of care therapy
  • Age 18 to less than 80 years
  • Cardiac ejection fraction ≥0.45
  • Karnofsky performance score ≥70
  • Expected survival >12 weeks
  • No supplemental oxygen requirement or dyspnea after effusion drainage

Key Exclusion

  • Breast, kidney, lung, pancreatic, prostate, ovarian, rare cancers, or melanoma
  • Active HIV, hepatitis B, or hepatitis C with viral replication
  • Active bacterial, fungal, or viral infection
  • Myocardial infarction within 6 months or symptomatic cardiac disease
  • Cytotoxic therapy or radiation within 2 weeks of effusion collection
  • Corticosteroids >10mg prednisone equivalent within 2 weeks
  • Significant laboratory abnormalities including AST/ALT >2x ULN, hemoglobin <8 gm/dL, platelets <100,000/mm3
  • Prior solid organ transplantation

NCT06745908

ResQ201A: Randomized, Open-Label, Phase 3 Clinical Trial of N-803 Plus Tislelizumab and Docetaxel Versus Docetaxel Monotherapy in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer Who Have Acquired Resistance to Immune Checkpoint Inhibitor Therapy Genomic-based

Organization/Sponsor: ImmunityBio, Inc.


Example patient: A 62-year-old with stage IV NSCLC harboring EGFR exon 19 deletion who progressed after 8 months of stable disease on pembrolizumab plus chemotherapy, previously treated with Osimertinib, ECOG 1, with measurable lung lesions.

Phase 3

Interventions

  • Chemotherapy: Docetaxel
    Summary: Docetaxel is a microtubule-targeting chemotherapy agent used in advanced NSCLC after platinum-based therapy failure, improving outcomes compared to vinca alkaloids (Web Search).
  • Immunotherapy: Tislelizumab
    Summary: Tislelizumab-jsgr is a PD-1-blocking monoclonal antibody that enhances anti-tumor immune responses by blocking the PD-1 pathway, approved for esophageal and gastric cancers (FDA label).
  • Immunotherapy: N-803
    Summary: N-803 is an IL-15 receptor agonist fusion protein that activates NK cells, CD8+ T-cells, and memory T-cells to enhance immune response against tumors with prolonged half-life (NCI Thesaurus).

Key Inclusion

  • Age ≥18 years
  • Pathologically confirmed stage IV NSCLC
  • Acquired resistance to immune checkpoint inhibitor after initial response or stable disease ≥6 months
  • Exactly 1 prior line of anti-PD-L1 or anti-CTLA-4 therapy
  • Participants with actionable genomic alterations (EGFR, ROS1, NTRK, BRAF, MET exon 14, RET, KRAS)
  • EGFR L858R or exon 19 deletion must have received prior Osimertinib
  • ECOG performance status 0-2
  • Measurable tumor lesions per RECIST v1.1

Key Exclusion

  • Systemic autoimmune disease currently requiring treatment
  • History of organ transplant requiring immunosuppression
  • Participants with ALK genomic alteration
  • Active hepatitis B or C infection
  • Active infection requiring antibiotic therapy
  • Severe hypersensitivity to docetaxel or polysorbate 80
  • Major surgery within 28 days prior to randomization
  • Inadequate organ function including absolute lymphocyte count <ULN, neutrophils <1500, platelets <100,000

NCT07139990

Personalized Radiotherapy for Individualized Treatment Strategies and Monitoring (PRISM): A Multi-cohort Platform Trial of Adaptive Radiotherapy Approaches in Multiple Cancer Types

Organization/Sponsor: University of Texas Southwestern Medical Center


Example patient: A 62-year-old with extensive stage small cell lung cancer diagnosed 90 days ago, ECOG status 1, currently on second cycle of chemoimmunotherapy, eligible for thoracic radiotherapy without prior chest radiation.

Phase N/A

Interventions

  • Radiation: Cohort B: Brain metastasis PULSAR (Personalized ultrahypofractionated stereotactic ablative radiotherapy)
    Summary: Personalized ultrahypofractionated stereotactic ablative radiotherapy delivers high-dose radiation to brain metastases in fewer sessions using precise targeting for effective local control. Source: Summary of Web Search.
  • Radiation: Cohort A: Extensive Stage Small Cell Lung Cancer (ES-SCLC) Thoracic Tumor PULSAR (Personalized ultrahypofractionated stereotactic ablative radiotherapy)
    Summary: Personalized ultrahypofractionated stereotactic ablative radiotherapy for extensive-stage small cell lung cancer thoracic tumors delivers high doses in fewer sessions to maximize tumor control while minimizing side effects. Source: Summary of Web Search.

Key Inclusion

  • Age 18 years or older
  • Cohort A: Extensive stage small cell lung cancer diagnosed by tissue biopsy within 180 days
  • Cohort A: ECOG performance status 0-2
  • Cohort A: Planned for or receiving standard chemoimmunotherapy with no more than 3 cycles
  • Cohort A: Able and indicated to receive thoracic radiotherapy
  • Cohort B: Solid tumor malignancy with MRI-defined brain metastases (1-5 lesions) within 60 days
  • Cohort B: Brain metastasis lesions 2-5 cm (brainstem lesions 1.5-5 cm)

Key Exclusion

  • Cohort A: Prior thoracic radiotherapy
  • Cohort B: Prior whole brain radiotherapy
  • Cohort B: Prior surgical resection or focal radiotherapy of target brain metastasis
  • Cohort B: Leptomeningeal disease

NCT07006727

A Phase I, Open-label, Multi-center Study to Evaluate the Safety, Tolerability, Dosimetry, and Preliminary Activity of [225Ac]Ac-ETN029 in Patients With Advanced DLL3-expressing Solid Tumors

Organization/Sponsor: Novartis


Example patient: A 62-year-old man with metastatic small cell lung cancer progressing after two lines of platinum-based chemotherapy, adequate bone marrow and renal function, no CNS metastases, and DLL3-positive tumor confirmed on imaging.

Phase I

Interventions

  • Radioligand Therapy: 111In-ETN029
    Summary: DLL3-targeting radioligand therapy delivering radioactive indium-111 to DLL3-expressing tumors for imaging and dosimetry assessment in lung cancer (Source: Web Search).
  • Radioligand Therapy: 225Ac-ETN029
    Summary: DLL3-targeting radioligand therapy using actinium-225 alpha-particle radiation to destroy DLL3-expressing cancer cells in lung and neuroendocrine tumors (Source: Web Search).

Key Inclusion

  • Age ≥ 18 years old
  • Locally advanced, unresectable, or metastatic SCLC with progression after ≥1 line including platinum chemotherapy
  • Dose escalation: LCNEC of lung with progression after ≥1 line including platinum chemotherapy
  • Dose expansion: NEPC with neuroendocrine differentiation confirmed by histology and IHC markers
  • Dose expansion: GEP-NEC with progression after ≥1 line including platinum chemotherapy
  • Dose expansion NEPC/GEP-NEC: Measurable lesion with 111In-ETN029 uptake on SPECT/CT
  • Prior DLL3-targeted therapy allowed for SCLC
  • Prior Lu-177 PSMA RLT allowed for NEPC

Key Exclusion

  • ANC < 1.0 x 10^9/L, hemoglobin < 9 g/dL, or platelets < 75 x 10^9/L
  • QTcF ≥ 470 msec
  • eGFR < 60 mL/min
  • Unmanageable urinary tract obstruction or urinary incontinence
  • Leptomeningeal disease or symptomatic CNS metastases requiring local therapy
  • History of or current interstitial lung disease or pneumonitis ≥ Grade 2
  • Prior DLL3-targeted therapy (except SCLC)
  • Prior RLT (except NEPC)

NCT07174583

A Multicenter Study Evaluating the Safety, Efficacy, and Pharmacokinetics of IDE849 in Patients With DLL3-Expressing Tumors Including Small Cell Lung Cancer Genomic-based

Organization/Sponsor: IDEAYA Biosciences


Example patient: A 62-year-old male with ECOG PS 1, DLL3-expressing metastatic SCLC progressed after two lines of platinum-based chemotherapy and PD-L1 inhibitor, with adequate organ function and no CNS metastases.

Phase N/A

Interventions

  • Drug: IDE849
    Summary: IDE849 is a DLL3-targeting antibody drug conjugate with a topoisomerase I inhibitor payload for small cell lung cancer treatment. It binds to DLL3-expressing tumor cells and delivers cytotoxic therapy. Source: Web Search.

Key Inclusion

  • Histologically or cytologically confirmed SCLC with progression after platinum-based therapy and PD-1/PD-L1 inhibitors
  • No more than 2 lines of previous systemic chemotherapy and no more than 3 total lines in recurrent/metastatic setting
  • Blood/tumor tissue samples required for biomarker testing
  • At least 1 measurable lesion per RECIST v1.1
  • ECOG Performance Status 0 or 1
  • Life expectancy greater than 3 months
  • Adequate bone marrow and organ function

Key Exclusion

  • Mixed SCLC and non-small cell lung cancer histology
  • Locally untreated or active CNS tumor metastasis
  • Prior treatment with DLL3 ADC or topoisomerase I inhibitor including ADC with topoisomerase I payload
  • History of interstitial pneumonitis or current noninfectious pneumonitis requiring steroids
  • Chemotherapy within 4 weeks or immunotherapy/biologic therapy within 2 weeks of first dose
  • Strong CYP3A4 inhibitors/inducers, CYP2D6 inhibitors, or P-gp/BCRP inhibitors within 2 weeks
  • Greater than 30 Gy chest radiotherapy within 12 weeks
  • Pregnant, lactating, or planning pregnancy during study

NCT07116057

Phase I Clinical Trial of Autologous Folate Receptor-Alpha Redirected T Cells in Patients With FRa+ Cancers Genomic-based

Organization/Sponsor: University of Pennsylvania


Example patient: A 62-year-old woman with ECOG 1, metastatic lung adenocarcinoma with malignant pleural effusion expressing FRa in 40% of tumor cells, who progressed after platinum-doublet chemotherapy and is eligible for checkpoint inhibitor therapy.

Phase 1

Interventions

  • Diagnostic Test: FRa Expression Testing
    Summary: Immunohistochemistry test identifying folate receptor alpha expression levels in tumor cells, used to determine eligibility for FRa-targeted therapy in lung adenocarcinomas (Summary of Web Search).
  • Drug: Cyclophosphamide/Fludarabine
    Summary: Lymphodepleting chemotherapy regimen that disrupts DNA synthesis and inhibits cell proliferation, used as conditioning prior to CAR T-cell infusion (Summary of Web Search).
  • Biological: MOv19-BBz CAR T cells
    Summary: Autologous T-cells transduced with lentiviral vector expressing anti-folate receptor alpha CAR with 4-1BB costimulatory domain and CD3-zeta signaling, targeting FRa-expressing tumor cells in NSCLC and other cancers (NCI Thesaurus).

Key Inclusion

  • Metastatic or recurrent lung adenocarcinoma with malignant pleural effusion
  • FRa expression ≥10% of tumor cells by IHC
  • Failure of at least one prior standard therapy
  • ECOG Performance Status 0 or 1
  • Age ≥18 years
  • Adequate organ function including LVEF ≥40%
  • Candidate for checkpoint inhibitor therapy
  • Asymptomatic treated CNS metastases allowed if stable

Key Exclusion

  • Significant lung disease including lymphangitic spread or interstitial lung disease
  • Active radiation pneumonitis
  • Dependence on systemic steroids or immunosuppressants
  • Active autoimmune disease requiring ≥10mg prednisone daily equivalent
  • Class III/IV cardiovascular disability
  • Active hepatitis B or C infection
  • Pregnant or nursing patients
  • Active invasive cancer within 2 years

NCT06671613

Evaluating the Impact of Intermittent Fasting in Combination With Checkpoint Inhibitors in Patients With Non-small Cell Lung Cancer Genomic-based

Organization/Sponsor: VA Office of Research and Development


Example patient: A 62-year-old veteran with newly diagnosed stage IV NSCLC, ECOG status 1, BMI 24, PD-L1 expression 65%, no recent weight loss, and no diabetes, preparing to start pembrolizumab monotherapy.

Phase N/A

Interventions

  • Dietary Intervention: Regular Diet Plus FMD
    Summary: A low-calorie, low-protein, high-complex carbohydrate, high-fat diet designed to enhance anticancer effects when combined with standard treatments and boost immune responses in cancer patients (Web Search).
  • Dietary Intervention: FMD
    Summary: Fasting-mimicking diet intervention used in combination with checkpoint inhibitors for cancer treatment.

Key Inclusion

  • Age 18 years or older
  • Newly diagnosed stage IV NSCLC
  • ECOG performance status 0-2
  • BMI 19 kg/m2 or greater
  • PD-L1 expression 50% or greater
  • Single agent pembrolizumab as checkpoint inhibitor
  • Enrolled prior to starting immunotherapy

Key Exclusion

  • Weight loss greater than 10% in 6 weeks prior to entry
  • History of symptomatic hypoglycemia or uncontrolled diabetes
  • Prior therapies with IGF-1 inhibitors
  • Concurrent use of somatostatin
  • Concurrent use of immunosuppressive medications
  • Significant food allergies
  • Pregnant or lactating females

NCT06941480

Characterizing the Theranostic Potential of DLL3-targeting Agents in High-grade Neuroendocrine Carcinomas of the Lung and Prostate Genomic-based

Organization/Sponsor: Memorial Sloan Kettering Cancer Center


Example patient: A 62-year-old man with metastatic small-cell lung cancer progressing after platinum-based chemotherapy, ECOG 1, with multiple liver and bone lesions ≥2cm showing DLL3 overexpression on imaging.

Phase N/A

Interventions

  • Radioligand Therapy: 177Lu-DTPA-SC16.56
    Summary: Targets DLL3 protein using lutetium-177 radioligand therapy to kill cancer cells in small-cell lung cancer and neuroendocrine carcinomas (Web Search).
  • Diagnostic Imaging: PET/CT
    Summary: Combines PET with CT using radioactive tracer for cancer detection, staging, tumor localization, and monitoring treatment response (Web Search).

Key Inclusion

  • Histologically proven progressive metastatic high-grade neuroendocrine carcinomas of lung (small-cell) or prostate
  • Relapsed following at least 1 line of standard chemotherapy
  • DLL3 overexpression with SUVmax greater than normal liver in ≥80% of progressing lesions ≥2cm
  • At least one tumor lesion ≥2cm on CT or MR
  • ECOG performance status 0 to 2
  • Disease progression within 3 months of study entry
  • Willingness to undergo baseline and follow-up biopsy
  • Adequate hematologic, renal, and hepatic function

Key Exclusion

  • Prior treatment with Rova-T (rovalpituzumab)
  • History of anaphylactic reaction to humanized or human antibodies
  • Uncontrolled brain metastases or carcinomatous meningitis
  • Unmanageable urinary incontinence
  • Life expectancy less than 6 months
  • Concurrent chemotherapy, other radiopharmaceuticals, or immunotherapy
  • Major surgery within 28 days
  • Other ongoing invasive malignancies with >30% relapse likelihood within 2 years

NCT04119024

Phase I Dose Escalation Study of Systemically Administered IL13Ra2 Chimeric Antigen Receptor (CAR) T Cells After a Nonmyeloablative Conditioning Regimen in Patients With Metastatic Melanoma and Other Solid Tumors Genomic-based

Organization/Sponsor: Stanford University


Example patient: A 52-year-old with stage IV melanoma expressing IL13Ralpha2, ECOG 1, who progressed after pembrolizumab and dabrafenib/trametinib combination therapy, with controlled brain metastases and adequate organ function.

Phase 1

Interventions

  • Biological: IL13Ralpha2-specific Hinge-optimized 4-1BB-co-stimulatory CAR/Truncated CD19-expressing Autologous TN/MEM Cells
    Summary: Genetically modified autologous T-cells targeting IL13Ralpha2-expressing tumors via a hinge-optimized CAR with 4-1BB co-stimulation and CD3-zeta signaling domains; includes CD19t marker for tracking; induces selective tumor cell cytolysis (NCI Thesaurus).
  • Drug: Fludarabine Phosphate
    Summary: Fluorinated nucleotide analog that inhibits DNA polymerase, ribonucleotide reductase, and DNA primase to interrupt DNA synthesis; used for lymphodepletion conditioning (FDA label, NCI Thesaurus).
  • Drug: Cyclophosphamide
    Summary: Alkylating agent converted to active metabolites that bind DNA and inhibit replication; used for lymphodepletion conditioning prior to CAR T-cell infusion (FDA label, NCI Thesaurus).
  • Diagnostic: Fludeoxyglucose F-18
    Summary: Positron-emitting radiopharmaceutical glucose analog for PET imaging; localizes to areas of increased glucose metabolism to assess tumor burden and treatment response (FDA label, NCI Thesaurus).
  • Procedure: Positron Emission Tomography
    Summary: Imaging technique measuring gamma radiation from positron-electron collisions to reveal metabolic activity in tissue; used for disease monitoring (NCI Thesaurus).
  • Procedure: Magnetic Resonance Imaging
    Summary: Imaging using radiofrequency waves and magnetic fields to visualize tumors and assess treatment response without radiation exposure (NCI Thesaurus).
  • Procedure: Computed Tomography
    Summary: X-ray based imaging constructing cross-sectional scans to examine internal structures and monitor disease progression (NCI Thesaurus).
  • Procedure: Biospecimen Collection
    Summary: Gathering of tissue or fluid samples for testing, research, and diagnostic purposes (NCI Thesaurus).
  • Procedure: Biopsy
    Summary: Removal of tissue specimens for microscopic examination to establish diagnosis and confirm IL13Ralpha2 expression (NCI Thesaurus).

Key Inclusion

  • Stage IIIC or IV melanoma or metastatic solid tumor refractory to standard therapies
  • IL13Ralpha2 tumor expression by IHC (H-Score ≥50 in ≥10% of tumor)
  • Age 18-75 years
  • ECOG performance status 0 or 1
  • Measurable disease by RECIST or photography
  • Melanoma patients must have progressed after immune checkpoint inhibitor and BRAF/MEK inhibitor if BRAF V600 mutated
  • Adequate organ function (ANC ≥1x10^9/L, platelets ≥75x10^9/L, hemoglobin ≥9.5 g/dL)
  • Willing to undergo leukapheresis

Key Exclusion

  • Systemic cancer treatment within 14 days of conditioning chemotherapy
  • Clinically active brain metastases
  • Systemic corticosteroids within 2 weeks or concurrent immunosuppressive drugs
  • HIV seropositivity or acquired immune deficiency
  • Active hepatitis B or C with liver damage
  • LVEF <45% or significant cardiac abnormalities
  • Tiffeneau-Pinelli index <70% predicted
  • Pregnancy or breastfeeding

NCT07166601

An Open Label, Multicenter, Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of M0324, a Bispecific (MUC-1 x CD40) Antibody as Monotherapy, in Combination With Pembrolizumab, and in Combination With Chemotherapy, in Participants With Selected Advanced Solid Tumors

Organization/Sponsor: EMD Serono


Example patient: A 58-year-old patient with metastatic pancreatic ductal adenocarcinoma overexpressing MUC-1, no prior systemic treatment for metastatic disease, adequate cardiac function, and life expectancy greater than 3 months.

Phase 1

Interventions

  • Biological: M0324
    Summary: M0324 is a bispecific antibody targeting MUC-1 and CD40, designed to enhance immune response against tumor cells through immune modulation and T-cell activation, studied in pancreatic and other solid tumors (Summary of Web Search).
  • Biological: Pembrolizumab
    Summary: Pembrolizumab is a humanized IgG4 monoclonal antibody that blocks PD-1 receptor, preventing interaction with PD-L1/PD-L2 and activating T-cell-mediated immune responses against tumors, FDA-approved for multiple cancers including NSCLC and melanoma (FDA label, NCI Thesaurus).
  • Drug: mFOLFIRINOX
    Summary: mFOLFIRINOX is a modified chemotherapy regimen combining fluorouracil, leucovorin, irinotecan, and oxaliplatin that inhibits DNA synthesis and repair, used for pancreatic, colorectal, and other adenocarcinomas (NCI Thesaurus, Summary of Web Search).

Key Inclusion

  • Advanced/metastatic solid tumors overexpressing MUC-1
  • Intolerant or refractory to standard therapy
  • No standard therapy judged appropriate by Investigator
  • Prior treatment with immune checkpoint inhibitors (Part 2)
  • Documented disease progression on or after ICIs (Part 2)
  • Previously untreated metastatic pancreatic ductal adenocarcinoma (Part 3)
  • Eligible for treatment with mFOLFIRINOX (Part 3)
  • No prior Whipple surgery or adjuvant chemotherapy (Part 3)

Key Exclusion

  • History of chronic diarrhea Grade 2 or greater
  • Inflammatory disease of colon or rectum
  • Unresolved intestinal obstruction
  • History of malignancy within 3 years before enrollment
  • Uncontrolled or poorly controlled arterial hypertension
  • Unstable angina, myocardial infarction, or congestive heart failure NYHA Grade II or greater
  • Coronary revascularization within 180 days of study entry
  • Life expectancy less than 3 months

NCT07146568

Evaluating the Implementation and Effectiveness of the Pink and Pearl Campaign on Lung Cancer Screening at Christian Hospital

Organization/Sponsor: Washington University School of Medicine


Example patient: A 62-year-old English-speaking woman with a 25 pack-year smoking history who quit 5 years ago, presenting for routine screening mammography at Christian Hospital without symptoms or prior lung cancer.

Phase N/A

Interventions

  • Behavioral: Pink and Pearl Campaign
    Summary: An awareness campaign integrating lung cancer risk assessment into breast cancer screening programs to enhance early detection through public communication via television, radio, newspapers, pamphlets, and telephone (NCI Thesaurus, Web Search).

Key Inclusion

  • Undergoing screening mammography at Christian Hospital
  • Between the ages of 50-80 years
  • 20 pack-year smoking history or quit within past 15 years
  • Can speak and understand English
  • Willing and able to get treatment if lung cancer is found

Key Exclusion

  • Previous history of lung cancer
  • Symptoms of lung cancer such as hemoptysis
  • Unexplained weight loss of more than 6.8 kg in the previous year
  • Serious health problem that will limit life expectancy

NCT07132918

The cARdiac Radiation Therapy Sparing (HEARTS) for Thoracic Cancers

Organization/Sponsor: University of Wisconsin, Madison


Example patient: A 62-year-old with stage IIIB non-operable non-small cell lung cancer requiring definitive radiotherapy with significant cardiac dose exposure, no prior thoracic radiation, and NYHA class I heart function.

Phase N/A

Interventions

  • Device: LINAC
    Summary: A particle accelerator generating ionizing radiation by colliding subatomic particles at high speeds to create high-energy radiation for cancer treatment (NCI Thesaurus).
  • Procedure: MRgART
    Summary: Magnetic resonance-guided adaptive radiation therapy utilizing MRI for detailed anatomic visualization immediately before or during radiation treatment (NCI Thesaurus).

Key Inclusion

  • Age > 18 years
  • Dosimetric criteria met: >10% of heart receives > 25 Gy
  • Stage IIIA/IIIB/IIIC non-operable non-small cell lung cancer
  • Stage I-III N0-2 esophageal/esophagogastric cancer
  • Stage II or III thymoma/thymic carcinoma
  • Definitive course of at least 15 fractions planned
  • Typical dose 1.8 to 4 Gy per fraction

Key Exclusion

  • Metastatic disease with life expectancy <12 months
  • Prior thoracic radiotherapy overlapping heart region
  • Contraindications to MRI
  • New York Heart Association Functional Classification III/IV

NCT06492954

Phase 1b Trial of Atezolizumab in Combination With Stereotactic Body Radiation Therapy (SBRT) and Surgery in Patients With Pulmonary Recurrence of Osteosarcoma

Organization/Sponsor: Emory University


Example patient: A 14-year-old with first relapse of osteosarcoma presenting with three resectable bilateral lung nodules (largest 8 mm), Lansky score 80, adequate organ function, and no extrapulmonary disease.

Phase 1

Interventions

  • Drug: Atezolizumab
    Summary: Atezolizumab is a humanized PD-L1 blocking monoclonal antibody that enhances T-cell-mediated immune response by preventing PD-L1 binding to PD-1 and B7.1, thereby reversing T-cell inactivation and promoting antineoplastic activity. FDA-approved for multiple cancers including NSCLC and melanoma, it is being studied in pediatric osteosarcoma. Source: FDA label, NCI Thesaurus.
  • Radiation: Stereotactic Body Radiation Therapy (SBRT)
    Summary: SBRT delivers high-dose, precise radiation to body tumors in one or several treatments, minimizing damage to surrounding tissues. Used in pediatric sarcomas and advanced diseases. Source: NCI Thesaurus, Web Search.
  • Procedure: Surgical Resection
    Summary: Surgical removal of all or part of an organ or tissue including lesions, used to completely excise localized tumors in pediatric cancer treatment. Source: NCI Thesaurus, Web Search.

Key Inclusion

  • Histologically verified osteosarcoma at original diagnosis or relapse
  • First or greater relapse of osteosarcoma
  • Recurrence limited to lung (unilateral or bilateral)
  • All pulmonary nodules resectable without pneumonectomy
  • At least 1 lesion ≥5 mm eligible for SBRT plus additional nodule(s) requiring surgical resection
  • Lansky/Karnofsky score ≥60 or ECOG ≤2
  • Adequate organ function including bone marrow, renal, hepatic, cardiac, and pulmonary
  • Negative pregnancy test and effective contraception for reproductive-age patients

Key Exclusion

  • Active metastatic disease outside lungs including bone, CNS, or extrapulmonary sites
  • Greater than Grade 1 pleural effusion
  • Prior lung radiation
  • Active autoimmune disorder requiring systemic treatment in past 12 months
  • Significant cardiovascular disease within 3 months
  • Chronic immunosuppressive therapies or uncontrolled infection
  • Prior allogeneic stem cell or solid organ transplant
  • Known HIV, hepatitis B/C, current or prior pneumonitis

NCT07218601

Electronic Nose (E-nose) Technology to Assess Pathologic Response and Post- Treatment Progression for Non-small Cell Lung Cancer: a Phase II Study

Organization/Sponsor: Memorial Sloan Kettering Cancer Center


Example patient: A 62-year-old with untreated stage IIIA NSCLC, ECOG performance status 1, scheduled for neoadjuvant chemotherapy followed by surgical resection.

Phase 2

Interventions

  • Procedure: Research blood collection
    Summary: Blood harvesting for clinical or manufacturing purposes (NCI Thesaurus).
  • Diagnostic Test: Breath sample collection
    Summary: Noninvasive collection of exhaled air to detect volatile organic compounds like hexanal, heptanal, and benzaldehyde for lung cancer detection and management (Web Search).

Key Inclusion

  • Age ≥18
  • Untreated clinical stage I NSCLC amenable to upfront surgery
  • Untreated stage II to IIIB NSCLC amenable to neoadjuvant treatment followed by surgery
  • ECOG Performance Status of ≤2

Key Exclusion

  • None

NCT07219251

Engagement of Veterans With Lung Cancer (EVLC)

Organization/Sponsor: Palo Alto Veterans Institute for Research


Example patient: A 62-year-old Spanish-speaking veteran with newly diagnosed stage III lung cancer starting chemotherapy and radiation at a VA oncology clinic.

Phase N/A

Interventions

  • Behavioral: Usual Care Group
    Summary: Standard treatment practices including conventional therapies like chemotherapy and radiation, serving as a control group without additional interventions (Summary of Web Search).
  • Behavioral: Lay Health Worker (LHW) Planning
    Summary: Community member providing support to the local health care system based on community needs and individual skill set (NCI Thesaurus).

Key Inclusion

  • Veteran patients with diagnosis of any stage of lung cancer
  • 18 years of age or older
  • English- or Spanish-speaking
  • Can self-administer questionnaires in English or Spanish
  • Valid telephone number
  • Receiving oncology care at participating sites
  • Newly diagnosed or receiving/completed systemic anti-cancer therapy and/or radiation therapy within 12 months

Key Exclusion

  • No capacity to consent
  • Actively receiving hospice care

NCT06816979

Assessing the CSF-ctDNA of Patients With Stage III and IV Non-Small Cell Lung Cancer: A Pilot Study Genomic-based

Organization/Sponsor: Ohio State University Comprehensive Cancer Center


Example patient: A 58-year-old male with newly diagnosed stage IV NSCLC harboring an EGFR mutation, no brain metastases, no prior cancer history, starting systemic therapy at Ohio State University with estimated survival over one year.

Phase N/A

Interventions

  • Procedure: Magnetic Resonance Imaging
    Summary: MRI uses radiofrequency waves and magnetic fields to visualize tumors, monitor treatment effects, and assess tumor size and relation to surrounding tissues without x-rays (NCI Thesaurus, Web Search).
  • Procedure: Lumbar Puncture
    Summary: Invasive procedure inserting a hollow needle through the lower back to access cerebrospinal fluid for cancer diagnosis and sampling (NCI Thesaurus, Web Search).
  • Procedure: Biospecimen Collection
    Summary: Collection of tissue or fluid samples for testing and research to study genetic features and identify disease patterns (NCI Thesaurus, Web Search).

Key Inclusion

  • New histological diagnosis of stage III or IV NSCLC
  • Documented mutation on lung cancer mutation panel (PULMOL) for stage III/IV without brain metastases
  • Treated with radiation therapy and/or systemic therapy at Ohio State University
  • Estimated survival >= 1 year
  • No medical contraindication to lumbar puncture

Key Exclusion

  • Alzheimer's, dementia, or mental disability
  • Not able to receive MRI
  • Allergy to xylocaine or numbing medication for lumbar puncture
  • Previous cancer history prior to NSCLC diagnosis
  • Pregnant or lactating women
  • Women of childbearing potential or sexually active men not using contraception

NCT07217301

A Randomized, Open-Label, Multicenter, Phase 3 Study Evaluating the Efficacy and Safety of IBI363 Versus Docetaxel in Participants With Unresectable Locally Advanced or Metastatic Squamous Non-Small Cell Lung Cancer With Disease Progression on or After Platinum-Based Chemotherapy and Anti-PD-1/PD-L1 Immunotherapy Genomic-based

Organization/Sponsor: Fortvita Biologics (USA)Inc.


Example patient: A 62-year-old male with metastatic squamous NSCLC, ECOG PS 1, who progressed 4 months after completing platinum-doublet chemotherapy plus pembrolizumab, with no actionable mutations and adequate organ function.

Phase 3

Interventions

  • Bispecific Antibody Fusion Protein: IBI363
    Summary: A bispecific antibody fusion protein targeting PD-1 and fused to mutated IL-2, designed to restore immune function by inhibiting PD-1-mediated signaling and activating cytotoxic T-lymphocytes and NK cells, enhancing tumor-specific T-cell responses while reducing IL-2 systemic toxicity (NCI Thesaurus).
  • Control Arm: Docetaxel
    Summary: Standard chemotherapy control arm for comparison with investigational treatment (NCI Thesaurus).

Key Inclusion

  • Locally unresectable advanced or metastatic squamous NSCLC
  • Resistant or refractory to platinum-based doublet chemotherapy and anti-PD-1/PD-L1 therapy
  • Radiographic progression per RECIST v1.1 during or within 6 months after anti-PD-1/PD-L1 discontinuation
  • At least one measurable lesion by CT or MRI per RECIST v1.1
  • ECOG PS score of 0 or 1
  • Expected survival time ≥ 3 months
  • Age ≥ 18 years or legal age of majority
  • Adequate hematologic, hepatic, and renal function

Key Exclusion

  • Known actionable genomic alterations including EGFR, KRAS G12C, ALK, ROS1, BRAF V600E, NTRK, MET exon 14, RET, HER2 mutations
  • Active or symptomatic brain metastases
  • Prior docetaxel treatment
  • Active autoimmune disease requiring systemic treatment within 2 years
  • History of ILD, pulmonary fibrosis, drug-related or radiation pneumonitis requiring steroids
  • Uncontrolled cardiovascular disease including QTc ≥ 480 ms, LVEF < 50%, NYHA Class II-IV heart failure
  • Active uncontrolled infection or fever ≥ 38°C within 2 weeks
  • Uncontrolled HIV, active hepatitis B or C, or tuberculosis

NCT07218003

An Open-Label, Multicenter, Phase 1/1b Study of RNDO-564 as Monotherapy and in Combination With Pembrolizumab in Adult Participants With Relapsed/Refractory Locally Advanced or Metastatic Urothelial Cancer and Other Solid Tumors Associated With Nectin-4 Expression Genomic-based

Organization/Sponsor: Rondo Therapeutics


Example patient: A 62-year-old woman with metastatic urothelial cancer expressing Nectin-4, progressed after platinum chemotherapy and one prior MMAE therapy, with Grade 1 peripheral neuropathy and adequate organ function.

Phase 1, Phase 1b

Interventions

  • Biological: Pembrolizumab
    Summary: Humanized monoclonal IgG4 antibody blocking PD-1 receptor to enhance T-cell immune responses against tumors; FDA-approved for melanoma, NSCLC, HNSCC, urothelial cancer, and other malignancies (FDA label, NCI Thesaurus).
  • Biological: RNDO-564
    Summary: Novel bispecific antibody targeting Nectin-4 and CD28 to induce tumor killing in Nectin-4 positive tumors including breast and urothelial cancers; under clinical investigation (Web Search).

Key Inclusion

  • Histologically documented incurable, locally advanced or metastatic solid tumors
  • Progressive disease on standard therapies or standard therapy not tolerated
  • Eligible tumor types: urothelial cancer, NSCLC, HNSCC, cervical cancer, gastric/GEJ cancer, esophageal cancer, TNBC
  • Up to 2 prior MMAE-containing therapies allowed if peripheral neuropathy Grade 2 or less
  • Measurable disease per RECIST v1.1
  • Adequate organ function

Key Exclusion

  • More than one prior Nectin-4 targeted agent
  • Peripheral neuropathy greater than Grade 2
  • History of or active inflammatory skin disease requiring biologics or oral steroids

NCT06861088

A Randomized, Placebo-Controlled, Double-Blind Phase 3 Trial Comparing, Relative to Placebo, the Effect of Kinisoquin on Thromboembolic Events in Patients With Metastatic Pancreatic Cancer (CATIQ P3)

Organization/Sponsor: Quercis Pharma AG


Example patient: A 62-year-old man with newly diagnosed metastatic pancreatic adenocarcinoma, ECOG status 1, starting FOLFIRINOX chemotherapy with no history of bleeding disorders or recent thromboembolic events.

Phase 3

Interventions

  • Drug: Kinisoquin
    Summary: Kinisoquin (Isoquercetin) is studied for preventing thromboembolic events in pancreatic cancer patients, potentially enhancing chemotherapy efficacy and inhibiting cancer growth (Web Search).
  • Other: Placebo
    Summary: Placebo is an inactive compound identical in appearance to the active treatment, used to distinguish drug action from suggestive effects (NCI Thesaurus).

Key Inclusion

  • Histologically or cytologically confirmed advanced metastatic pancreatic adenocarcinoma
  • Receiving first line chemotherapy within 30 days of first study drug dose
  • Age 18 years or older
  • Life expectancy greater than 6 months
  • ECOG performance status ≤2
  • Adequate organ and marrow function
  • Willingness to use contraception during study participation

Key Exclusion

  • Known brain metastases
  • Thromboembolic event within last 2 years
  • Active bleeding or high bleeding risk
  • Currently receiving anticoagulant therapy
  • Daily aspirin >81mg, clopidogrel, or high-dose NSAIDs
  • Known intolerance to isoquercetin, niacin, or ascorbic acid
  • Uncontrolled intercurrent illness or active infection
  • Pregnancy or lactation

NCT06974604

Prevention of Datopotamab Deruxtecan (TROP-2 Directed ADC) Associated Stomatitis in Patients With HER2-negative Metastatic Breast Cancer or Non-small Cell Lung Cancer Using Dexamethasone Mouthwash: a Single-arm, Phase 2 Trial (TROPION- DM, 2023-ESR-000087) Genomic-based

Organization/Sponsor: Brown University


Example patient: A 62-year-old woman with metastatic triple negative breast cancer progressed after first-line chemotherapy, ECOG 1, LVEF 55%, adequate organ function, no oral pain, and no history of interstitial lung disease.

Phase 2

Interventions

  • Drug: Datopotamab deruxtecan
    Summary: TROP-2 directed antibody-drug conjugate used for treatment of advanced metastatic cancer including HER2-negative breast cancer and non-squamous NSCLC; mentioned in eligibility criteria as primary therapeutic agent.
  • Drug: Dexamethasone mouthwash
    Summary: Topical corticosteroid mouthwash used prophylactically to prevent stomatitis associated with Datopotamab deruxtecan therapy; primary intervention being studied in this trial.

Key Inclusion

  • Advanced/metastatic non-squamous NSCLC progressed on at least one prior therapy
  • Triple negative breast cancer progressed on at least 1 prior line
  • Hormone receptor positive breast cancer progressed on CDK4/6 inhibitor and 1 prior chemotherapy line
  • Age ≥18 years with ECOG performance status 0-2
  • LVEF ≥50% by ECHO or MUGA within 28 days
  • Measurable disease by RECIST 1.1
  • Adequate organ function including platelets ≥100,000/mm3, ANC ≥1000/mm3
  • Baseline oral pain VAS score 0 and normalcy diet scale ≥60

Key Exclusion

  • History of non-infectious ILD/pneumonitis requiring steroids or current ILD
  • Clinically significant corneal disease
  • Severe hypersensitivity to monoclonal antibodies or polysorbate 80
  • Uncontrolled infection requiring IV antibiotics
  • Active poorly controlled HIV, hepatitis B or C infection
  • Pregnancy or lactation
  • Uncontrolled cardiac disease including MI within 6 months or NYHA Class II-IV heart failure
  • Severe pulmonary compromise from autoimmune or inflammatory disorders

NCT07190248

A Phase 3, Randomized, Open-label, Multicenter Clinical Study to Evaluate the Safety and Efficacy of MK-1084 in Combination With Subcutaneous Pembrolizumab and Berahyaluronidase Alfa (MK-3475A) Versus MK-3475A in Combination With Pemetrexed/Platinum (Carboplatin or Cisplatin) Chemotherapy as First-line Treatment of Participants With KRAS G12C-Mutant, Advanced or Metastatic Nonsquamous NSCLC (KANDLELIT-007) Genomic-based

Organization/Sponsor: Merck Sharp & Dohme LLC


Example patient: A 62-year-old patient with newly diagnosed Stage IV nonsquamous NSCLC harboring KRAS G12C mutation with no prior systemic therapy for metastatic disease and no active autoimmune conditions.

Phase 3

Interventions

  • Drug: MK-1084
    Summary: An orally available KRAS G12C inhibitor that selectively targets the KRAS G12C mutation, inhibiting KRAS-mediated signaling to halt tumor cell proliferation and metastasis in susceptible cancers (NCI Thesaurus).
  • Biological: Pembrolizumab (+) Berahyaluronidase alfa
    Summary: A fixed-combination immunotherapy containing pembrolizumab (PD-1 blocking antibody) and berahyaluronidase alfa (hyaluronidase for subcutaneous delivery) that enhances anti-tumor immune responses by blocking PD-1 pathway in multiple advanced cancers (FDA label).
  • Drug: Pemetrexed
    Summary: A folate analog metabolic inhibitor that disrupts cancer cell proliferation by inhibiting thymidylate synthase and other enzymes involved in nucleotide synthesis, indicated for non-squamous NSCLC treatment (FDA label, NCI Thesaurus).
  • Drug: Carboplatin
    Summary: A second-generation platinum compound that forms DNA cross-links causing apoptosis and cell growth inhibition, with tumoricidal activity similar to cisplatin but more stable and less toxic (NCI Thesaurus, FDA label).
  • Drug: Cisplatin
    Summary: A platinum-based alkylating-like agent that forms DNA cross-links inducing apoptosis and cell growth inhibition, used for treating advanced cancers with monitoring for nephrotoxicity and ototoxicity (FDA label, NCI Thesaurus).

Key Inclusion

  • Nonsquamous NSCLC Stage IIIB, IIIC not eligible for curative resection or chemoradiation, or Stage IV (M1a, M1b, M1c)
  • KRAS G12C-mutant tumor
  • Advanced or metastatic disease
  • First-line treatment setting
  • HIV positive patients with well controlled HIV on antiretroviral therapy allowed

Key Exclusion

  • Small cell lung cancer or mixed tumors with small cell elements
  • Prior systemic anticancer therapy for advanced or metastatic NSCLC
  • Active CNS metastases or carcinomatous meningitis
  • Active autoimmune disease requiring systemic treatment in past 2 years
  • History of pneumonitis/interstitial lung disease requiring steroids or current pneumonitis
  • Active inflammatory bowel disease requiring immunosuppressive medication
  • Uncontrolled cardiovascular or cerebrovascular disease
  • History of stem cell or solid organ transplant

NCT06996782

A Phase Ib/II Open-Label, Multicentre Platform Study Evaluating Novel Combinations in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer Genomic-based

Organization/Sponsor: AstraZeneca


Example patient: A 62-year-old patient with newly diagnosed Stage IV non-squamous NSCLC, PD-L1 TPS 50%, no EGFR/ALK alterations, adequate organ function, and no prior systemic therapy for metastatic disease.

Phase 1b, Phase 2

Interventions

  • BLA: Ramucirumab
    Summary: A human monoclonal antibody targeting VEGFR-2 that inhibits tumor angiogenesis and vascular growth, approved for multiple advanced cancers including NSCLC in combination with chemotherapy (FDA label, NCI Thesaurus).
  • Drug: Nab-paclitaxel
    Summary: A Cremophor-free, albumin-stabilized nanoparticle formulation of paclitaxel that disrupts microtubules and inhibits cell division, approved for first-line metastatic NSCLC with carboplatin (NCI Thesaurus, Web Search).
  • Drug: Paclitaxel
    Summary: A microtubule inhibitor that binds tubulin and prevents spindle formation, disrupting cell division and inducing apoptosis, indicated for NSCLC in combination with cisplatin (FDA label, NCI Thesaurus).
  • Drug: Pemetrexed
    Summary: A folate analog metabolic inhibitor that disrupts nucleotide synthesis by inhibiting thymidylate synthase, indicated for non-squamous NSCLC in combination with pembrolizumab and platinum chemotherapy (FDA label, NCI Thesaurus).
  • Drug: Carboplatin
    Summary: A second-generation platinum compound that forms DNA crosslinks and induces apoptosis, used in combination regimens with comparable efficacy to cisplatin but improved tolerability (FDA label, NCI Thesaurus).
  • Drug: Cisplatin
    Summary: A platinum-based alkylating agent that forms DNA intrastrand and interstrand crosslinks leading to apoptosis, indicated for advanced cancers including lung cancer (FDA label, NCI Thesaurus).
  • Biological: AB248
    Summary: An investigational CD8+ T cell selective IL-2 agent designed to enhance anti-tumor immune activity by targeting specific immune cells (Web Search).
  • Biological: Rilvegostomig
    Summary: A bispecific antibody targeting PD-1 and TIGIT that restores T-cell function and enhances CD226-mediated immune responses against cancer cells by blocking dual immune checkpoints (NCI Thesaurus).

Key Inclusion

  • Confirmed squamous or non-squamous NSCLC with current Stage IV metastatic disease
  • PD-L1 tumor proportion score (TPS) ≥ 1% per local report
  • Measurable disease with at least one lesion ≥ 10 mm at longest diameter
  • Archival or fresh tumor tissue biopsy mandatory at screening
  • Minimum life expectancy of 12 weeks
  • Adequate organ and marrow function with minimum body weight of 30 kg

Key Exclusion

  • EGFR mutations, ALK fusions, or other genomic alterations with approved first-line targeted therapy
  • Any prior systemic therapy for advanced or metastatic NSCLC
  • Prior exposure to anti-PD-1, anti-PD-L1, anti-CTLA-4, or anti-TIGIT therapy
  • Active autoimmune disease requiring systemic treatment in past 2 years
  • History of non-infectious pneumonitis requiring steroids or current pneumonitis/interstitial lung disease (Sub Study 1)
  • Unresolved toxicities Grade ≥ 2 from prior anti-cancer therapy or symptomatic brain metastases
  • History of another primary malignancy unless treated with curative intent and no active disease ≥ 2 years
  • Active tuberculosis infection or uncontrolled systemic diseases including uncontrolled hypertension