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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 Melanoma.


Overview

Number of Trials: 8

These eight trials investigate advanced melanoma (cutaneous, uveal, mucosal, acral) and other solid tumors using immunotherapy, targeted agents, CAR T-cell therapy, and liver-directed approaches. Most focus on metastatic or relapsed/refractory disease, with several exploring novel antibody-drug conjugates, checkpoint inhibitors (pembrolizumab, nivolumab, ipilimumab), and combination strategies. One trial tests neoadjuvant immunotherapy with surgical approaches, another evaluates circadian timing of immunotherapy, and one examines a dietary supplement (sulforaphane) for melanoma prevention in high-risk patients. Uveal melanoma is addressed in two trials using darovasertib and tebentafusp-tebn with liver-directed therapies.

Common Criteria Across Trials

Common Inclusion

  • Age ≥18 years
  • ECOG performance status 0-1 or 0-2
  • Histologically or cytologically confirmed melanoma (cutaneous, uveal, mucosal, or acral)
  • Adequate organ and marrow function (ANC ≥1000-1500/mcL, platelets ≥75,000-100,000/mcL, bilirubin ≤2x ULN, AST/ALT ≤2.5-3x ULN, creatinine clearance ≥60 mL/min)
  • Measurable disease per RECIST or RANO criteria
  • Life expectancy >3-6 months
  • Willingness to use contraception during study and for 4-6 months after last dose
  • Written informed consent

Common Exclusion

  • Active autoimmune disease requiring systemic treatment in past 2 years
  • Systemic steroid therapy >10 mg prednisone daily or immunosuppressive therapy within 7-14 days
  • Active or uncontrolled infections requiring IV antibiotics within 2 weeks
  • Known HIV, active hepatitis B or C infection
  • Symptomatic or untreated brain metastases (stable treated metastases allowed)
  • Leptomeningeal disease
  • Pregnant or breastfeeding women
  • Prior malignancy active within 3 years (except adequately treated non-melanoma skin cancer or carcinoma in situ)
  • Major surgery within 2-3 weeks
  • Radiotherapy within 2-4 weeks (palliative radiation to limited fields allowed)
  • Prior investigational drugs within 21-28 days

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


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 HER3-positive cutaneous melanoma refractory to standard therapy, ECOG performance status 1, body weight 65 kg, with no history of pneumonitis or active brain metastases.

Phase 1, Phase 2

Interventions

  • Antibody-Drug Conjugate: ENV-501
    Summary: ENV-501 is a HER3-targeted antibody-drug conjugate composed of a humanized monoclonal antibody conjugated via a hydrophilic cleavable linker to exatecan, a DNA topoisomerase I inhibitor. Upon binding to HER3-expressing tumor cells, it is internalized and releases exatecan, inhibiting DNA replication and causing apoptosis. Source: NCI Thesaurus and Web Search.

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

NCT04129515

Phase I and II Study of NovoTTF-200A and Pembrolizumab in Newly Diagnosed Melanoma Brain Metastasis Genomic-based

Organization/Sponsor: Brown University


Example patient: A 52-year-old with BRAF-mutant melanoma who progressed on dabrafenib/trametinib, now presenting with three newly diagnosed brain metastases (largest 2.5 cm), ECOG 1, no leptomeningeal disease, and a family caregiver available for device support.

Phase 1, Phase 2

Interventions

  • Biological: Pembrolizumab
    Summary: Humanized monoclonal IgG4 antibody that blocks PD-1 receptor on T-cells, preventing binding of PD-L1/PD-L2 ligands and enhancing immune-mediated tumor destruction; FDA-approved for melanoma and other cancers (FDA label, NCI Thesaurus).
  • Device: NovoTTF-200A
    Summary: Device delivering low-intensity alternating electric fields (tumor-treating fields/TTFields) to disrupt cancer cell division in brain tumors; requires at least 75% daily wear time (Web Search).

Key Inclusion

  • Histologically confirmed melanoma metastatic to brain (M1d)
  • At least 1 untreated brain metastasis, maximum diameter 3 cm
  • Age 18 or above
  • ECOG performance status 0-1 or Karnofsky ≥80
  • BRAF mutated patients must have progressed on or not tolerate BRAF/MEK therapy
  • Willing to comply with NovoTTF-200A device for at least 75% of time
  • Available caregiver to assist with transducer array exchange
  • Archival or newly obtained tissue available

Key Exclusion

  • Leptomeningeal metastasis
  • Systemic steroids >4 mg daily dexamethasone equivalent within 7 days
  • Implanted pacemaker, defibrillator, deep brain stimulator, or significant arrhythmias
  • Evidence of increased intracranial pressure (midline shift >5mm, papilledema, reduced consciousness)
  • Active autoimmune disease requiring systemic treatment in past 2 years
  • Chemotherapy, radiotherapy, or anti-cancer mAb within 4 weeks
  • Hypersensitivity to pembrolizumab or hydrogel
  • Pregnant or breastfeeding women

NCT07155317

The TIME Trial - Phase II Randomized Controlled Trial of Time-of-Day Specified Immunotherapy for Advanced Melanoma

Organization/Sponsor: Emory University


Example patient: A 52-year-old with ECOG 1 performance status and stage IV unresectable cutaneous melanoma with small asymptomatic brain metastases, previously treated with BRAF/MEK inhibitors but no recent immunotherapy.

Phase II

Interventions

  • Drug: Nivolumab
    Summary: A fully human IgG4 monoclonal antibody that blocks PD-1 receptor, preventing interaction with PD-L1/PD-L2 and enhancing T-cell activation and immune response against melanoma and other cancers (FDA label, NCI Thesaurus).
  • Drug: Ipilimumab
    Summary: A recombinant human IgG1 monoclonal antibody that blocks CTLA-4 on T-cells, preventing immune downregulation and enhancing cytotoxic T-lymphocyte response against cancer cells (FDA label, NCI Thesaurus).
  • Procedure: Questionnaire Administration
    Summary: Administration of questionnaires to assess patient-reported outcomes, experiences, and symptoms during treatment (NCI Thesaurus).
  • Procedure: Magnetic Resonance Imaging
    Summary: Imaging using radiofrequency waves and magnetic fields to provide detailed pictures of internal organs and tissues for cancer diagnosis and monitoring (NCI Thesaurus).
  • Procedure: Computed Tomography
    Summary: Diagnostic imaging method using X-rays and computer reconstruction to create cross-sectional scans for tumor visualization, staging, and disease monitoring (NCI Thesaurus).
  • Procedure: Biospecimen Collection
    Summary: Collection of blood or tissue samples for research, testing, and diagnostic purposes to study disease mechanisms and treatment responses (NCI Thesaurus).
  • Procedure: Biopsy Procedure
    Summary: Removal of tissue specimens for microscopic examination to establish diagnosis, including excisional or incisional methods for melanoma (NCI Thesaurus).
  • Other: Medical Device Usage and Evaluation
    Summary: Classification term for medical device usage and performance evaluation in clinical settings (NCI Thesaurus).

Key Inclusion

  • AJCC 8th edition stage IV unresectable cutaneous, acral, or mucosal melanoma
  • Asymptomatic, non-hemorrhagic brain metastases less than 2 cm
  • No prior immunotherapy within 1 year
  • BRAF/MEK inhibitors allowed
  • ECOG performance status 0-1
  • Age 18 years or older
  • Adequate organ function to receive ipilimumab/nivolumab

Key Exclusion

  • Uveal melanoma
  • Immunosuppression (greater than 10mg prednisone daily)
  • Active autoimmune disease precluding immunotherapy
  • Active leptomeningeal disease

NCT07049276

Randomized Controlled Trial of Selective Index Lymph Node Resection Versus Therapeutic Lymph Node Dissection After Neoadjuvant Immunotherapy for Stage IIIB-D Melanoma

Organization/Sponsor: Melanoma Institute Australia


Example patient: A 52-year-old with ECOG 0 status and resectable Stage IIIC cutaneous melanoma with palpable axillary lymph nodes, scheduled for neoadjuvant pembrolizumab, no prior immunotherapy or autoimmune disease.

Phase N/A

Interventions

  • Procedure: Therapeutic lymph node dissection
    Summary: Surgical removal of all or part of lymph nodes draining the area around a tumor to eliminate regional metastatic disease (NCI Thesaurus).
  • Procedure: Index lymph node resection
    Summary: Targeted resection of the primary cancerous lymph node following neoadjuvant immunotherapy to assess treatment effectiveness and prevent cancer spread in stage III melanoma (Web Search Summary).

Key Inclusion

  • Age ≥18 years
  • Resectable pathological Stage IIIB, C or D cutaneous or unknown primary melanoma
  • At least one macroscopic lymph node confirmed by pathology
  • Lymph node involvement in groin, axilla or neck only
  • Neoadjuvant immunotherapy with PD-(L)-1 checkpoint inhibitor scheduled
  • ECOG performance status 0-1
  • Life expectancy >5 years
  • Up to 3 satellite or in-transit metastases if completely resectable

Key Exclusion

  • Uveal or mucosal melanoma
  • Distant metastasis (any M stage)
  • Prior anti-PD-1, CTLA-4, PDL-1 or LAG-3 antibody exposure
  • Previous lymph node surgery more extensive than sentinel lymph node biopsy
  • Active autoimmune disease requiring immunosuppressive therapy
  • Known additional active malignancies within 3 years
  • Pregnant or breastfeeding
  • Active Hepatitis B, Hepatitis C, or known HIV

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 IL13Ra2, BRAF V600 mutant, who progressed after pembrolizumab and dabrafenib/trametinib combination, with ECOG 1 and controlled brain metastases post-radiation.

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 IL13Ra2-expressing tumors via a hinge-optimized CAR with 4-1BB co-stimulation and CD3-zeta signaling, inducing selective tumor cell cytolysis; CD19t marker enables in vivo tracking (NCI Thesaurus).
  • Drug: Fludeoxyglucose F-18
    Summary: Positron-emitting radiopharmaceutical for PET imaging that localizes to areas of increased glucose metabolism, producing gamma photons detectable by scanners to assess malignancy and treatment response (FDA label).
  • Procedure: Positron Emission Tomography
    Summary: Imaging technique measuring gamma radiation from positron-electron collisions to reveal tissue location of metabolically-active substances, used for monitoring disease and treatment response (NCI Thesaurus).
  • Procedure: Magnetic Resonance Imaging
    Summary: Imaging using radiofrequency waves and magnetic fields to provide detailed pictures of internal organs and tissues, valuable for diagnosing cancer and monitoring treatment effects (NCI Thesaurus).
  • Drug: Fludarabine Phosphate
    Summary: Fluorinated nucleotide analog that inhibits DNA polymerase, ribonucleotide reductase, and DNA primase, interrupting DNA synthesis; used for lymphodepletion conditioning prior to CAR T-cell therapy (FDA label, NCI Thesaurus).
  • Drug: Cyclophosphamide
    Summary: Alkylating agent converted to active metabolites that bind DNA, inhibiting replication and initiating cell death; used for nonmyeloablative lymphodepletion conditioning before CAR T-cell infusion (FDA label, NCI Thesaurus).
  • Procedure: Computed Tomography
    Summary: Imaging method using X-rays and computer reconstruction to create cross-sectional scans for examining internal body structures and monitoring disease progression (NCI Thesaurus).
  • Procedure: Biospecimen Collection
    Summary: Process of gathering tissue or fluid samples for testing, diagnostic, research, or treatment purposes to study disease patterns and genetic features (NCI Thesaurus).
  • Procedure: Biopsy
    Summary: Removal of tissue specimens or fluid from the living body for microscopic examination to establish diagnosis and confirm tumor IL13Ra2 expression (NCI Thesaurus).

Key Inclusion

  • Stage IIIC or IV melanoma surgically incurable
  • IL13Ralpha2 tumor expression H-Score ≥50 in ≥10% of tumor
  • Age 18-75 years
  • ECOG performance status 0 or 1
  • Melanoma patients progressed after ≥1 line systemic therapy including checkpoint inhibitor
  • BRAF V600 mutant patients must have failed BRAF/MEK inhibitor combination
  • At least one measurable lesion per RECIST
  • Adequate organ function: ANC ≥1x10^9/L, platelets ≥75x10^9/L, creatinine <2 mg/dL

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
  • Hepatitis B or C with ongoing liver damage
  • Left ventricular ejection fraction <45%
  • Pregnancy or breastfeeding
  • Concomitant active malignancy interfering with study assessment

NCT07040280

A Phase II Double-Blind Trial of Sulforaphane for Therapeutic Prevention of Melanoma in Patients With Multiple Atypical Nevi and a Prior History of Melanoma

Organization/Sponsor: Eastern Cooperative Oncology Group


Example patient: A 52-year-old man with five atypical nevi and a history of resected stage IB melanoma two years ago, not currently on immunotherapy and without allergies to cruciferous vegetables.

Phase II

Interventions

  • Dietary Supplement: Sulforaphane (broccoli sprout extract)
    Summary: A cruciferous vegetable extract containing sulforaphane, an isothiocyanate that activates transcription factor Nrf2 to induce antioxidant enzymes for carcinogen detoxification and chemoprevention (NCI Thesaurus).
  • Placebo Comparator: Placebo
    Summary: An inactive compound identical in appearance to sulforaphane used to distinguish drug action from suggestive effects in this double-blind trial (NCI Thesaurus).
  • Diagnostic Tool: Derma-AI
    Summary: An AI-driven tool using machine learning models to enhance diagnostic accuracy and speed for melanoma and skin cancer detection (Summary of Web Search).

Key Inclusion

  • ≥3 clinically atypical nevi ≥5mm with macular component
  • Prior diagnosis of early-stage melanoma (in situ, stage I-II node negative, or low-risk resected stage III)
  • Not on targeted or checkpoint immunotherapy within 365 days
  • Age ≥18 years
  • HIV-infected patients with undetectable viral load on therapy eligible
  • Chronic HBV with undetectable viral load on suppressive therapy eligible
  • HCV patients treated and cured or with undetectable viral load on treatment eligible
  • Prior or concurrent malignancy eligible if not interfering with study safety or efficacy

Key Exclusion

  • Pregnancy
  • Known allergy to cruciferous vegetables
  • Use of other sulforaphane-containing dietary supplements during study
  • Current systemic treatment for melanoma

NCT06626516

A Phase I/II Study of Tebentafusp-tebn in Combination With Liver-Directed Therapies for the Treatment of Metastatic Uveal Melanoma Genomic-based

Organization/Sponsor: Thomas Jefferson University


Example patient: A 52-year-old HLA-A*0201-positive patient with treatment-naïve metastatic uveal melanoma involving 30% of the liver with the largest lesion measuring 4 cm, ECOG status 0, and normal organ function.

Phase 1, Phase 2

Interventions

  • Drug: BCNU
    Summary: BCNU is an alkylating agent that inhibits cell division by alkylating DNA and RNA, used in hepatic chemoembolization for melanoma liver metastases (Summary of Web Search).
  • Biological: GM-CSF (Sargramostim)
    Summary: GM-CSF stimulates immune cell production to enhance melanoma treatment, used in hepatic immunoembolization and as adjuvant therapy to augment immune checkpoint inhibitors (Summary of Web Search).
  • Biological: Tebentafusp-Tebn
    Summary: Tebentafusp-tebn is a bispecific T-cell engager targeting HLA-A*02:01/gp100 that redirects T cells to kill melanoma cells, approved for metastatic uveal melanoma in HLA-A*02:01-positive patients (Summary of Web Search).

Key Inclusion

  • Age ≥18 years
  • Histologically or cytologically confirmed metastatic uveal melanoma in the liver
  • At least one measurable liver metastasis ≥10 mm
  • HLA-A*0201 positive
  • ECOG performance status 0 or 1
  • Part 1: Treatment naïve in metastatic setting, tumor <50% liver involvement, largest tumor ≤5 cm
  • Part 2: May have had up to two prior lines of treatment
  • Adequate organ and bone marrow function

Key Exclusion

  • Prior tebentafusp-tebn use
  • Prior chemoembolization in Part 2
  • Symptomatic liver failure including ascites or hepatic encephalopathy
  • Symptomatic or untreated CNS metastases requiring corticosteroids within 21 days
  • Active hepatitis B or C infection
  • Systemic steroid therapy or immunosuppressive medication
  • Biliary obstruction or main portal vein occlusion
  • Part 1 only: History of severe hypersensitivity to GM-CSF

NCT07015190

A Randomized, Phase 3, Open-label Study of Neoadjuvant Darovasertib in Subjects With Primary Non-metastatic Uveal Melanoma (OptimUM-10)

Organization/Sponsor: IDEAYA Biosciences


Example patient: A 58-year-old with newly diagnosed primary non-metastatic uveal melanoma, ECOG 0, adequate organ function, no prior treatment, and no evidence of metastases or other malignancies.

Phase 3

Interventions

  • Drug: Darovasertib
    Summary: An orally available protein kinase C (PKC) inhibitor that binds and inhibits PKC, preventing activation of PKC-mediated signaling pathways, leading to cell cycle arrest and apoptosis in tumor cells (NCI Thesaurus).
  • Procedure: Primary Local Therapy
    Summary: Any therapeutic procedure that targets or is restricted to a specific anatomical location (NCI Thesaurus).

Key Inclusion

  • Primary non-metastatic uveal melanoma
  • ECOG performance status 0 or 1
  • Adequate organ function
  • Able to provide written informed consent

Key Exclusion

  • Previous treatment for uveal melanoma
  • Evidence of metastatic uveal melanoma
  • Attributes necessitating enucleation regardless of response
  • Progressive secondary ocular disease confounding visual acuity assessments
  • Presence of other malignant disease