a study of the safety and tolerance of can04 and pembrolizumab in combination with and without carboplatin and pemetrexed in subjects with solid tumors

Conditions: Carcinoma, Non-Small-Cell Lung; Urothelial Carcinoma; Malignant Melanoma; Head and Neck Squamous Cell Carcinoma

Summary: this study will consider the safety and effectiveness of a study drug, can04, in combination with pembrolizumab, in the treatment of incurable or metastatic non-small-cell lung cancer (nsclc), head and neck squamous cell carcinoma, urothelial cancer, or malignant melanoma. the study aims to establish a recommended dose of can04 in combination with the standard dose of pembrolizumab (part 1), and in combination with pembrolizumab standard dose, and standard of care carboplatin and pemetrexed (part 2 - subjects with stage iv, non-squamous metastatic nsclc). can04, pembrolizumab. carboplatin and pemetrexed will be administered intravenously.


Eligibility criteria:
inclusion criteria (part 1): * subjects with metastatic or locally advanced, incurable non-small-cell lung cancer (nsclc \[adenocarcinoma, adenosquamous, or squamous\]), head and neck squamous cell carcinoma (hnscc), urothelial cancer, or malignant melanoma who have exhausted or declined available standard therapy. * subjects progressing on previous treatment with a checkpoint inhibitor targeting thepd-1/pd-l1 pathway, alone or in combination with chemotherapy after previously having achieved stable disease or better and stayed on such therapy for ≥12 weeks. * primary or metastatic lesion suitable for biopsy and willingness to undergo repeat biopsies as appropriate. * willing and able to provide intravenous access for the administration of the study drug and for blood sampling/testing. inclusion criteria (part 2): * subjects with histologically confirmed non-squamous metastatic (stage iv) nsclc, without option for locoregional treatment with curative intent. * subjects who have not received prior systemic anti-cancer therapy for the locally advanced or metastatic nsclc. subjects who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 12 months prior to the development of metastatic disease. * ability to safety undergo pre-treatment (if no archival biopsy is available) and on-treatment tumor biopsies. * subject consents to retrieval of archival tumor tissue for screening in case no fresh biopsy is performed during screening. * willing and able to provide intravenous access for the administration of the study drug and for blood sampling/testing. exclusion criteria (parts 1 and 2): * subjects with nsclc tumors with genetic alteration or mutation, for which fda-approved targeted therapy is available. * treatment with systemic anticancer treatments, investigational products, or major surgery within 4 weeks before first dose of study drug or 5 half-lives, whichever is shorter. subjects should have recovered from previous treatment toxicity (except hair loss and peripheral neuropathy). * history of uncontrolled brain metastasis. * subject has received extended field radiotherapy ≤4 weeks before the start of treatment (≤2 weeks for limited field radiation to alleviate symptoms), and who has not recovered from related side effects of such therapy (except for hair loss). * subjects who have previously experienced an immune-related adverse event (irae) to pembrolizumab, for which permanent discontinuation is required. subjects without a formal contraindication due to previous irae are not eligible if the ae has not resolved or requires steroids (\>10 mg prednisone-equivalent per day) for ongoing management. * subjects with active severe infection requiring oral antibiotics. * clinical evidence of an active second invasive malignancy with the exception of stable prostate cancer on watchful waiting. * uncontrolled or significant cardiovascular disease. * history of autoimmune disease requiring systemic immunosuppressive therapy (daily prednisone equivalent doses \>10 mg/day). * hiv patients can be enrolled if the infection is adequately controlled. * known bleeding disorder or coagulopathy. subjects on stable anticoagulant therapy are allowed. * known or suspected allergy to study treatment or related products. * women who are pregnant or breastfeeding, or trying to become pregnant. * patients with chronic viral hepatitis. exclusion criteria (part 2): * previous therapy with immunotherapy (anti-pd-1, anti-pd-l1, and anti-pd-l2, anti-ctla-4, or other approved or investigational checkpoint-inhibitors). * subject is unable or unwilling to take folic acid or vitamin b12 supplementation. * subject is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (nsaids), other than an aspirin dose ≤ 1.3 g per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam). other protocol-defined inclusion/exclusion criteria may apply.

Keywords: nsclc adenocarcinoma of lung lung cancer squamous cell lung cancer malignant melanoma urothelial cancer non-small-cell lung cancer non small cell lung cancer non-small-cell lung carcinoma non small cell lung carcinoma hnscc head and neck squamous cell carcinoma