Phase 2 DoceRamPem for Patients With Metastatic or Recurrent NSCLC Who Progressed on Platinum-Doublet and PD-1/PD-L1 Blockade

Description

PRIMARY OBJECTIVE:

I. To determine the anti-tumor efficacy of the combination treatment using the 6-month progression free survival rate by Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

SECONDARY OBJECTIVES:

I. To determine the safety profile and tolerability of docetaxel and ramucirumab in combination with pembrolizumab in patients who progressed on platinum-based chemotherapy and PD-1 or PD-L1 checkpoint inhibitor given sequentially or in combination.

II. To determine immune related adverse events of the combination docetaxel, ramucirumab, and pembrolizumab.

III. To assess the overall response rate (ORR) of the combination docetaxel, ramucirumab, and pembrolizumab.

IV. To assess the overall survival (OS) of the combination docetaxel, ramucirumab, and pembrolizumab.

EXPLORATORY OBJECTIVES:

I. To correlate treatment response with PD-L1 22C3 expression, STK11 and KRAS mutation status.

II. To correlate treatment response with the doublet tumor mutation burden (TMB) and PD-L1 22C3 expression.

III. To perform an immunophenotypic analysis of circulating immune cells by mass cytometry before and after treatment and end of treatment (EOT).

IV. To analyze the tumor infiltrating immune cells by mass cytometry coupled to blood mass cytometry, in paired biopsies before and at end of after treatment.

OUTLINE:

After premedication, patients will receive docetaxel intravenously (IV) over 60 minutes, ramucirumab IV over 60 minutes, then pembrolizumab IV over 30 minutes on day 1 of each 21-day cycle. The combination will be administered until confirmed disease progression defined as progression on 2 consecutive scans at least 4 weeks apart, occurrence of severe side effects, withdrawal of consent by the patient or if in the opinion of the treating physician continuing on the study treatment is not in the best interest of the patient.

The first six patients will be evaluated for safety data. If less than 2 patients experience dose limiting toxicity, enrollment on study will continue with the efficacy assessment of the combination.

Participants who experience confirmed disease progression or start a new anticancer therapy, will move into the Survival Follow-Up Phase and should be contacted by telephone every 12 weeks (+/- 3 weeks) for 2 years, then every 6 months for next 3 years, then annually until the subject’s death or until the subject is lost to follow-up up to 10 years to assess for survival status until death, withdrawal of consent, or the end of the trial, whichever occurs first.