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

Stage IV Lung Cancer AJCC v8 Clinical Trial

Official title: A Phase 2 Study of Docetaxel, Ramucirumab, and Pembrolizumab for Patients With Metastatic or Recurrent Non-Small Cell Lung Cancer Who Progressed on Platinum-Doublet and PD-1/PD-L1 Blockade

Status Recruiting

Clinical Trial Summary

This phase 2 trial will evaluate the safety and efficacy of combining immunotherapy with a PD-1 checkpoint inhibitor (Pembrolizumab), an anti-VEGF receptor (Ramucirumab), and a taxane chemotherapy (Docetaxel) in treating patients with non-small cell lung cancer (NSCLC) who did not respond to FDA-approved treatments with platinum-based chemotherapy given concurrently or sequentially with anti-PD1/PD-L1 immunotherapy.

Pembrolizumab helps the body's immune system to attack cancer cells and hinder their ability to grow and spread. Ramucirumab blocks new blood vessel growth to reduce tumor growth. Docetaxel works mainly by stopping cancer cells from dividing. Ramucirumab combined with docetaxel is an FDA-approved therapy for NSCLC patients after progression on platinum-based chemotherapy. It has shown to improve efficacy compared to docetaxel alone in this setting. Pembrolizumab is an FDA-approved treatment for NSCLC and can be given alone or in combination with platinum-based chemotherapy.

Investigators hypothesize that the combination of docetaxel, ramucirumab, and pembrolizumab will be safe and more effective than the current standard of care treatments (docetaxel alone or in combination with ramucirumab) in patients with metastatic or recurrent NSCLC after progression on treatment with platinum-based chemotherapy and immunotherapy, given concurrently or sequentially.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Lung Neoplasms
• Metastatic Non-Small Lung Cell Cancer
• Recurrence
• Recurrent Non-Small Lung Cell Cancer
• Stage IV Lung Cancer AJCC v8
• Stage IVA Lung Cancer AJCC v8
• Stage IVB Lung Cancer AJCC v8

• NCT number: NCT04340882
• Study type: Interventional
• Source: Emory University
• Contact: Badi El Osta, MD, FACP
• Phone: 404-778-4964
• Email: belosta@emory.edu
• Status: Recruiting
• Phase: Phase 2
• Start date: June 5, 2020
• Completion date: December 31, 2030