Clinical Trial 19344

Cancer Type:
Interventions:FPV-CV301; MVA-BN-CV301; Pembrolizumab (Keytruda)

Study Type: Treatment
Phase of Study: Phase I
Investigators:

  • Jhanelle Gray

Overview

Study Title

A Phase 1/2 Trial of CV301 in Combination with Anti-PD-1 Therapy versus Anti-PD-1 Therapy alone in Subjects with Non-Small Cell Lung Cancer

Summary

The purpose of this clinical trial is to investigate the combination of CV301 (an experimental cancer vaccine) with Anti-PD-1 Therapy (Pembrolizumab) for treatment of non-small cell lung cancer. In Phase 1b Pembrolizumab will be used. In Phase 2 Pembrolizumab will be used. Pembrolizumab is an Anti-PD-1 Therapy which was approved as of June 2017 for first-line treatment of NSCLC.

Objective

Phase 1: To assess the safety and identify the recommended dose of CV301 for the next development phases. Phase 1b: Cohort 1: To assess the safety, tolerability, and dose of CV301 in combination with Nivolumab. Cohort 2: To assess the safety, tolerability, and dose of CV301 in combination with Pembrolizumab. Phase 2: To assess the safety and preliminary efficacy of CV301 in combination with Pembrolizumab maintenance compared to Pembrolizumab maintenance alone in subjects with NSCLC as measured by overall survival (OS).

Inclusion Criteria

  • Criteria is for phase 1b and phase 2 participation.
  • Histologically confirmed non-squamous Non-small Cell Lung Cancer (SCLC), metastatic or unresectable locally advanced. Actionable Epidermal Growth Factor Receptor (EGFR) mutations and ALK/ROS-1 translocations targetable with FDA approved therapy must be evaluated and found not to be present by standard methods. Expression of PD-L1 must have been determined with a validated method or tumor sample must be available for PD-L1 expression determination.
  • Patient population: Phase 1b, Cohort 1 (Nivolumab + CV301): Patients with progression on or after prior platinum, with or without switch maintenance chemotherapy are eligible. Phase 1b, Cohort 2 and Phase 2 (Pembrolizumab + CV301): Patients must have been on Pembrolizumab as first-line therapy for NSCLC as per FDA approved indications in first line for at least 11 weeks and assessed by RECIST to have CR, PR, or SD at week 12 (+/- 1 week).
  • As of June 2017, FDA-approved indications for front-line treatment include 2 indications for Pembrolizumab: 1.) As a single agent for the first-line treatment of patients with metastatic NSCLC whose tumors have high PD-L1 expression (Tumor Proportion Score (TPS) ≥50%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations. 2.) In combination with pemetrexed and carboplatin, as first-line treatment of patients with metastatic nonsquamous NSCLC. This indication is approved under accelerated approval based on tumor response rate and progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. Pemetrexed single agent maintenance after the initial 4 cycles of pemetrexed in combination with carboplatinum and Pembrolizumab is allowed and optional as per investigator or institutional standard practice.
  • In case of metastatic recurrence of a previous early stage NSCLC, any chemotherapy or radiation therapy must have finalized more than 12 months before the start of the first-line treatment, either Pembrolizumab alone or in combination with pemetrexed and carboplatinum.
  • ECOG performance status 0 and 1.
  • Men or women, age ≥ 18 years
  • Normal organ and marrow function
  • Have measurable disease by computed tomography (CT)/Magnetic resonance imaging (MRI) per RECIST 1.1.
  • Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
  • Able to understand and be willing to sign a written informed consent document.
  • Must have, prior to trial treatment, at least 10 unstained tissue slides (or a tissue block from which 10 slides can be cut) from a prior biopsy or surgical resection for submission for research purposes. Optional for Phase 1b. Mandatory for Phase 2.

  • Exclusion Criteria

  • EGFR mutations, ALK or ROS-1 translocations candidates to targeted therapy.
  • Squamous histology of NSCLC.
  • Other concurrent investigational agents (eligible to enroll 4 weeks after completion of prior investigational agent).
  • More than 1 prior chemotherapy regimen for locally advanced or metastatic NSCLC with the exception of the Phase 1 portion, in which multiple therapies are allowed in all tumor types. Any prior chemotherapy regimen different from pemetrexed-carboplatinum in combination with Pembrolizumab as first-line chemotherapy for candidates to Pembrolizumab maintenance of first line (Phase 1b and Phase 2).
  • Concurrent chemotherapy or radiotherapy or other immunotherapy not explicitly allowed by inclusion criteria for that phase of study.
  • Treated with PD-1/L1 or any other experimental immunotherapeutic agents outside the parameters established in the inclusion criteria, are excluded from enrollment into Phase 1b and 2, but can be enrolled into Phase 1.
  • Other malignancy within last 5 years with an estimated risk of recurrence higher than 50%.
  • Metastatic lesions in the brain.
  • History of allergy or untoward reaction to prior vaccination with vaccinia virus, aminoglycoside antibiotics or egg products; history of allergy to smallpox vaccination.
  • Active infection within 72 hours prior to vaccination.
  • Known evidence of being immunocompromised.
  • Altered immune function, including, but not limited to: inflammatory bowel disease; active infectious enteritis; eosinophilic enteritis; lupus erythematosus; ankylosing spondylitis; scleroderma; multiple sclerosis. These criteria do not include all diseases with an immune-related component, but are not auto-immune in nature or have a primary alteration in the general immune function that may interfere with the vaccine mechanism of action, for example celiac disease.
  • Concurrent chronic use of systemic steroids, except for physiologic doses of systemic steroids for replacement, defined as 5 mg of prednisone per day or equivalent, or local (topical, nasal, ophthalmic or inhaled) steroid use or prior concomitant use with chemotherapy. Systemic steroids must have been discontinued ≥ 2 weeks prior to randomization. Prior use of corticoids in short-term schemes (duration shorter than 3 days) for indications such as prophylaxis of reactions to intravenous contrast for imaging studies or chemotherapy-related AEs are not considered part of this exclusion. Prior use of corticoids for brain metastasis ending before day -14 is not considered part of this exclusion criteria.
  • Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
  • Women who are pregnant or breastfeeding.
  • Clinically significant cardiomyopathy, coronary disease, heart failure New York Heart Association class III or IV, or cerebrovascular accident within 1 year.
  • Uncontrolled intercurrent illness, which would interfere with the ability of the subject to carry out the treatment program.
  • Additional criteria may apply.