A Trial of CV301 in Combination With Anti-PD-1 Therapy in Subjects With Non-Small Cell Lung Cancer

NCT02840994 | Completed Phase 1

• 2 other identifiers: CV301-2015-201MAGNI-LUNG-01
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 7

Brief Summary

The objective of the proposed clinical trial is to investigate the safety and tolerability of CV301 in combination with Anti-PD1-Therapy in subjects with non-small cell lung cancer (NSCLC). The clinical trial is designed to evaluate the possible enhanced antitumor activity of CV301 with Anti-PD1-Therapy. The rationale for combining CV301 with Anti-PD1-Therapy is based on the hypothesis that CV301 can induce specific immune response in the tumor, and that in combination, Anti-PD1-Therapy may augment the T cell-mediated immune response generated by CV301 by blocking the inhibitory signal of the PD-1. The trial will include a Phase 1 portion and a Phase 1b portion with 2 cohorts. The Phase 1 portion is a dose escalation part to assess the safety and tolerability of CV301 alone, prior to moving into the combination with Anti-PD1-Therapy (the Phase 1b component). The following Phase 1b portion of the trial aims to test the safety and tolerability of the combination treatment using a two cohort approach with cohort 1 receiving CV301 plus Nivolumab and cohort 2 receiving CV301 plus Pembrolizumab.

Conditions

Non-small Cell Lung Cancer (NSCLC)

Keywords

CV301, NSCLC, Pembrolizumab, Nivolumab

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of CV301 alone and in combination determined by incidence of dose-limiting toxicities (DLTs)

  Safety and tolerability following administration of CV301 alone (Phase 1) and in combination with Nivolumab or Pembrolizumab (Phase 1b), respectively, as determined by the incidence of dose-limiting toxicities (DLTs).

  Through study completion, up to 2 years

Study Arms (2)

CV301 + Pembrolizumab

EXPERIMENTAL

CV301 + Pembrolizumab (Phase 1b portion of the trial)

Biological: CV301; Biological: Pembrolizumab

CV301 + Nivolumab

EXPERIMENTAL

CV301 + Nivolumab (Phase 1b portion of the trial)

Biological: CV301; Biological: Nivolumab

Interventions

CV301 BIOLOGICAL

CV301 + Nivolumab; CV301 + Pembrolizumab

Pembrolizumab BIOLOGICAL

Also known as: KEYTRUDA

CV301 + Pembrolizumab

Nivolumab BIOLOGICAL

Also known as: OPDIVO

CV301 + Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have a metastatic or unresectable locally advanced malignant solid tumor, histologically confirmed by the Laboratory of Pathology, NCI. Efforts will be made, as much as possible, to enroll subjects with tumor types with known increased expression of CEA or MUC-1 (such as lung, breast, ovarian, prostate, colorectal, pancreatic, bladder, gastric, cervix, etc.).
• Subjects may have measurable or nonmeasurable but evaluable disease. Subjects with surgically resected or ablated metastatic disease at high risk of relapse are also eligible.
• Prior therapy: Subjects must have completed or had disease progression on at least one prior line of disease-appropriate therapy for locally advanced or metastatic disease, or not be candidates for therapy of proven efficacy for their disease.
• Subjects with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations.
• There should be a minimum of 4 weeks from any prior chemotherapy, immunotherapy and/or radiation, with the exception of hormonal therapy for prostate and breast cancers, HER2-directed therapy for HER2+ breast cancer (3+ IHC or FISH+), maintenance therapy for colorectal or pancreatic cancer, and erlotinib therapy in EGFR-mutated lung cancer under the condition that subjects are on these therapies for at least two months before start of trial treatment. There should be a minimum of 6 weeks from any prior antibody therapies (such as ipilimumab or Anti-PD1/PDL1) due to prolonged half-life.
• Subjects must have recovered (Grade 1 or baseline) from any clinically significant toxicity associated with prior therapy. Typically, this is 3-4 weeks for subjects who most recently received cytotoxic therapy, except for nitrosoureas and mitomycin C, for which 6 weeks is needed for recovery.
• Men or women, age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 or Karnofsky ≥ 70%, (see Section 19.1, Appendix I and Section 19.2, Appendix II).
• Subjects must have normal organ and marrow function as defined below
• a. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) OR creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below): i. Female CrCl = \[(140 - age in years) x weight in kg x 0.85\] / \[72 x serum creatinine in mg/dL\] ii. Male CrCl = \[(140 - age in years) x weight in kg x 1.00\] / \[72 x serum creatinine in mg/dL\] b. Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 3 x the ULN c. Total bilirubin ≤ 1.5 x ULN OR in subjects with Gilbert's syndrome, a total bilirubin ≤ 3.0 x ULN d. Hematological eligibility parameters (within 16 days of starting therapy): i. Platelet count ≥ 100,000/µL ii. Absolute neutrophil count (ANC) ≥ 1/ µL
• Subjects must have baseline pulse oximetry \> 90% on room air.
• The effects of CV301 on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to trial entry and for the duration of trial participation and for a period of 4 months after the last vaccination. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this trial, she should inform her treating physician immediately.
• Subjects with prostate cancer must continue to receive GnRH agonist therapy (unless orchiectomy has been done).
• Subjects must be able to understand and be willing to sign a written informed consent document.
• Histologically confirmed non-squamous NSCLC, metastatic or unresectable locally advanced. Actionable 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.

You may not qualify if:

• Subjects with EGFR mutations, ALK or ROS-1 translocations candidates to targeted therapy.
• Squamous histology of NSCLC.
• Other concurrent investigational agents (subjects are 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).
• Other malignancy within last 5 years with an estimated risk of recurrence higher than 50%. Examples of low risk of recurrence malignancies are non-melanoma skin cancer, in situ cervical, superficial bladder cancer, colorectal cancer stage I and II, breast cancer stages I and II, prostate cancer stages I and II, etc.
• Patients with 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.
• Subjects should have no known evidence of being immunocompromised as listed below:
• Human immunodeficiency virus (HIV) positivity, chronic hepatitis infection, including hepatitis B and C virus
• Active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
• Immunosuppressive therapy post-organ transplant
• 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.
• Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
• Pregnant or breastfeeding women.

Sponsors & Collaborators

• Bavarian Nordic: lead

Study Sites (7)

H. Lee Moffitt Cancer Center & Research Institute, Inc.

Tampa, Florida, 33612, United States

Location

Investigative Clinical Research of Indiana

Indianapolis, Indiana, 46260, United States

Location

Metairie Oncologist, LLC

Metairie, Louisiana, 70006, United States

Location

NCI

Bethesda, Maryland, 20892, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Novant Health Oncology Specialists

Winston-Salem, North Carolina, 27103, United States

Location

Millennium Oncology

Houston, Texas, 77090, United States

Location

Related Publications (1)

• Rajan A, Gray JE, Devarakonda S, Birhiray R, Korchin B, Menius E, Donahue RN, Schlom J, Gulley JL. Phase 1 trial of CV301 in combination with anti-PD-1 therapy in nonsquamous non-small cell lung cancer. Int J Cancer. 2023 Feb 1;152(3):447-457. doi: 10.1002/ijc.34267. Epub 2022 Sep 9.

  PMID: 36054490 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab; Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Cesar Pico-Navarro, MD

  Bavarian Nordic

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2016
• First Posted: July 21, 2016
• Study Start: December 1, 2016
• Primary Completion: January 1, 2020
• Study Completion: January 1, 2020
• Last Updated: February 27, 2020

Record last verified: 2020-02

Locations

US (7)