Brief Summary
Intervention / Treatment
- Drug: Nemvaleukin Alfa Subcutaneousunder the skin
- Drug: Nemvaleukin Alfa Intravenousinto or within a vein
- Drug: Nemvaleukin Alfa Intravenous Less Frequent Dosing
- Drug: Pembrolizumab
Inclusion Criteria:
- The patient must have the following tumor types:
Cohort 1: Patient has unresectable and/or metastatic cutaneous melanoma. No more than 5 patients with acral melanoma may enroll in this cohort.
Cohort 2: Patient has unresectable and/or metastatic mucosal melanoma.
Cohort 3: Patient has unresectable and/or metastatic cutaneous melanoma. Patients with acral melanoma may not enroll in this cohort.
Cohort 4: Patient has unresectable and/or metastatic cutaneous melanoma. No patients with mucosal or acral melanoma may enroll in this cohort.
– The patient must have received previous treatment as follows: Cohorts 1 and 2: Patient has received anti-PD-[L]1 therapy with or without anti-CTLA-4 therapy, and less than or equal to one other prior regimen of systemic anti-neoplastic therapy (eg, targeted therapymedication that targets specific molecular features of cancer cells, chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells). Previous adjuvant and/or neoadjuvant therapy counts as one prior regimen. Patients have experienced objective response (partial response [PR] or CR; by RECIST 1.1 or iRECIST) or stable disease (SD; by RECIST 1.1 or iRECIST) as best overall response (BOR) to anti-PD-[L]1 therapy. Patients with confirmed progressive disease (by RECIST 1.1 or iRECIST) as best response may be included, if they received anti-PD-[L]1 therapy for a minimum of 12 weeks (eg, from first dosethe amount of medication taken to last dose). Patients with BRAF mutations may or may not have received prior targeted therapy.
Cohort 3: Patients who have received anti-PD-[L]1 therapy with or without anti-CTLA-4 therapy or anti-lymphocyte-activation gene 3 (LAG-3) therapy, and ≤1 other prior regimen of systemic anti-neoplastic therapy (eg, targeted therapy, chemotherapy). Previous adjuvant and/or neoadjuvant therapy counts as 1 prior regimen. Patients must have experienced objective response (PR or CR by RECIST 1.1 or iRECIST) or stable disease (by RECIST 1.1 or iRECIST) as BOR to anti PD-[L]1 therapy. Patients with confirmed progressive disease (by RECIST 1.1 or iRECIST) as best response may be included, if they received anti-PD-[L]1 therapy for ≥12 weeks (from first dose to last dose). Patients with BRAF mutations may or may not have received prior targeted therapy.
Cohort 4: Patients must not have received prior systemic anticancer therapy for unresectable or metastatic melanoma. Prior adjuvant and/or neoadjuvant PD-[L]1 treatments are allowed if there is at least 6 months between the last dose and date of recurrenceto occur or happen again.
Cohorts 1, 2, and 3 – Patients who have received prior treatment with talimogene laherparepvec (TVEC) are allowed to enroll provided that last exposure to TVEC was ≥28 days prior to first exposure to nemvaleukin and that all injection-site reactions to TVEC have resolved. TVEC shall not be considered a prior regimen of systemic anti-neoplastic therapy, nor shall it be considered a systemic immunomodulatory agent.
- Patients must have disease that is measurable based on RECIST 1.1., that has not recently been irradiated or used to collect a biopsyremoval of a section of tissue to analyse for cancer cells.
- Cohorts 1 and 2 (required), Cohort 3 (optional), Cohort 4 (may be required, otherwise optional). Patient is willing to undergo a pretreatment tumor biopsy or provide qualifying archival tumor tissuea group of cells that work together to perform a function.
Cohort 4 – Patients are required to have known tumor PD-[L]1 status determined by local testing using an approved assay. PD-[L]1 testing performed prior to enrolling on the study is acceptable if there was no intervening systemic anti-cancer therapy, and archival tissue may be used for testing provided the biopsy is ≤3 months old.
- Patient has an Eastern Cooperative Oncologythe study, diagnosis and treatment of cancer Group (ECOG) status of 0 or 1 and an estimated life expectancy of ≥3 months.
- Additional criteria may apply.