less frequent iv dosing & tumor microenvironment (tme) study of nemvaleukin alfa (alks 4230) monotherapy and in combination with pembrolizumab (artistry-3)

Conditions: Advanced Solid Tumor

Summary: the study will be conducted in 2 cohorts. a single-center design for the tumor microenvironment (tme) cohort (cohort 1), and a multicenter design for the less frequent intravenous (iv) dosing cohort (cohort 2).


Eligibility criteria:
inclusion criteria: * patients must have histologically or cytologically confirmed diagnosis of an advanced solid tumor type of cutaneous melanoma, rcc, tnbc, mss colorectal cancer, msi-h solid tumors (nos), or ovarian cancer with at least 1 accessible lesion for biopsy (cohort 1 tme) * patients must have histologically or cytologically confirmed epithelial tumor of the fallopian tube, peritoneum, or ovaries, cervical cancer, endometrial cancer, non-small cell lung adenocarcinoma, small cell lung cancer, gastric and gastroesophageal junction adenocarcinoma, esophageal cancer (squamous and adeno cell type), pancreatic cancer, biliary tract tumor (including intra- and extrahepatic cholangiocarcinoma, gall bladder, ampullary type), cutaneous melanoma, mucosal melanoma, head and neck squamous cell carcinoma, or metastatic or advanced breast cancer after treatment failure or intolerance of 1 to 3 established indication specific therapies (cohort 2) * patient must have received 1 to 3 prior fda-approved targeted therapies, failure of adjuvant and neoadjuvant therapy is considered 1 line of treatment * all patients' baseline biopsies must be taken no more than 3 months before screening and at least 4 weeks after completion of last antineoplastic therapy * patients must have at least 1 lesion that qualifies as a target lesion * patients must have adequate hematologic reserve * patients must have adequate hepatic and renal function * for cohort 1 (tme) and part a of cohort 2 (less frequent iv dosing), treatment with prior immunotherapy is permitted unless the patient has previously experienced grade ≥3 autoimmune toxicity or drug-related toxicity requiring discontinuation. patients in part b of cohort 2 (less frequent iv dosing) who received prior anti-pd-(l)1 for at least 3 months may enroll if they had a response of stable disease or better * for cohort 1 (tme), patients who have received prior anti-pd-1 directed therapy must wait at least 4 weeks from last dose of such therapy before the screening biopsy is collected * women of childbearing potential (wocbp) must have a negative pregnancy test * additional criteria may apply exclusion criteria: * patients with active or symptomatic central nervous system metastases * patients who require pharmacologic doses of systemic corticosteroids (greater than 10 mg of prednisone daily or equivalent) * patients known to be positive for hiv and/or history of hepatitis b, or c infections or is known to be positive for hepatitis b antigen (hbsag)/hepatitis b virus (hbv) dna or hepatitis c antibody (hep c ab) or rna. * patients with a known additional malignancy within 2 years of the start of screening * patients who have received radiotherapy within the last 4 weeks before start of study treatment * patients who have received systemic immunomodulatory agents within 4 weeks or 5 half lives, whichever is shorter, before cycle 1 day 1, * patients who have received prior il-2-based or il-15-based soluble protein therapy at any time in the past are excluded * additional criteria may apply

Keywords: alkermes il-2 interleukin-2 oncology immuno-oncology cytokine pembrolizumab keytruda pd-l1 solid tumors immunotherapy nemvaleukin