GEN-001 (Live Biotherapeutic Product) and Avelumab Combination Study for Patients With Solid Tumors Who Have Progressed on Anti-PD-(L)1 Therapy

NCT04601402 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: [GNC] GEN001-101
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 3

Brief Summary

This is a phase I/Ib, first-in-human (FIH), open-label, dose escalation and dose expansion study to evaluate the safety and tolerability, biological and clinical activities of GEN-001 in patients with locally advanced or metastatic solid tumors who have progressed on at least two lines of approved therapy for their histological subtypes which includes an anti-PD-1 or anti-PD-L1 based therapy (as mono or combination), when administered as combined with avelumab.

Conditions

Solid Tumor; Non Small Cell Lung Cancer; Squamous Cell Carcinoma of Head and Neck; Urothelial Carcinoma

Outcome Measures

Primary Outcomes (4)

• Dose Escalation: Incidence of Adverse Events

  Assessed as per CTCAE v5.0

  1 years

• Dose Escalation: Incidence of Laboratory abnormalities

  Assessed as per CTCAE v5.0

  1 years

• Dose Escalation: Incidence of dose-limiting toxicity (DLT)

  To evaluate the safety and tolerability of GEN-001 in combination with avelumab

  1 Cycle (one cycle = 28 days)

• Dose Expansion: To assess objective response (OR) of GEN-001 in patients with advanced or metastatic solid tumors, when administered as combined with avelumab.

  Confirmed OR per RECIST v1.1 by the Investigator

  2 years

Secondary Outcomes (7)

• Objective Response (OR)

  1 years

• Duration of response (DoR)

  up to 2 years

• Progression-free survival (PFS)

  up to 2 years

• Overall Survival (OS)

  up to 2 years

• Incidence of Adverse Events

  up to 2 years

Other Outcomes (3)

• Ctrough

  up to 2 years

• ADA

  up to 2 years

• Microbiota

  up to 2 years

Study Arms (1)

GEN-001 with avelumab

EXPERIMENTAL

Dose Escalation Cohort includes patients with advanced or metastatic solid tumors who have progressed on at least two lines of approved therapy for their histological subtypes which includes an anti-PD-1 or anti-PD-L1 based therapy (as mono or combination) will be enrolled. 3 or 6 patients will be enrolled per escalating or de-escalating dose levels. Dose Expansion Cohort includes patients with advanced or metastatic NSCLC, SCCHN, and UC who have progressed on at least two lines of approved therapy for their histological subtypes which includes an anti-PD-1 or anti-PD-L1 based therapy (as mono or combination)will be enrolled.

Drug: GEN-001; Drug: Avelumab

Interventions

GEN-001 DRUG

The capsules taken by mouth once a daily. Each capsule will contain ≥ 1x10\^11 colony-forming units (CFU)

GEN-001 with avelumab

Avelumab DRUG

800 mg given by intravenous (IV) infusion once every 2 weeks

Also known as: Bavencio

GEN-001 with avelumab

Eligibility Criteria

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

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Have adequate organ functions as defined in the protocol
• Negative childbearing potential
• Have ability to swallow and retain oral medication and no clinically significant gastrointestinal abnormalities
• Patients with diseases for which no curative therapies are available, and who have progressed on at least two lines of approved therapy for their histological subtypes which includes an anti-PD-1 or anti-PD-L1 based therapy (as mono or combination)
• Disease progression on anti-PD-(L)1 based therapy (as monotherapy or combination therapy) and must meet criteria for acquired resistance as defined in the protocol
• Patients who have completely recovered from any clinically significant AEs that occurred during prior immunotherapy
• Estimated life expectancy of at least 3 months
• Objective evidence of disease progression at baseline (Dose Escalation)
• Histologically or cytologically confirmed, unresectable, locally advanced, or metastatic NSCLC, SCCHN, and UC (Dose Expansion)
• Measurable disease as per RECIST v1.1 defined as at least 1 lesion (Dose Expansion)

You may not qualify if:

• Have experienced primary resistance to anti-PD-(L)1 based therapy
• Has experienced a toxicity that led to permanent discontinuation of prior anti-PD-(L)1 based therapy or other immunotherapies
• Has active autoimmune disease that has required systemic treatment in the past 2 years
• Current use of immunosuppressive medication at time of study entry
• Have an active infection requiring antibiotics, antifungal or antiviral agents or have received a course of antibiotics within the previous 4 weeks of starting study treatment
• Has received a live vaccine within 4 weeks of starting of study treatment
• Known history of, or any evidence of active, non-infectious pneumonitis
• Prior solid organ or allogeneic stem cell transplantation
• Has had any investigational or anti-tumor treatment within 4 weeks or 5 half-life periods of starting study treatment, had any major surgeries within 4 weeks of starting study treatment
• Has received proton pump inhibitors (PPIs) within 2 weeks prior to dosing study treatments
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has clinically significant (i.e., active) cardiovascular disease
• Has known history of uncontrolled intercurrent illness
• Has any psychiatric condition that would prohibit the understanding or rendering of informed consent or that would limit compliance with study requirements.

Sponsors & Collaborators

• Genome & Company: lead
• Merck KGaA, Darmstadt, Germany: collaborator
• Pfizer: collaborator

Study Sites (3)

Yale Cancer Center

New Haven, Connecticut, 06510, United States

Location

Emory University Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Transitional Cell

Interventions

avelumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms

Study Officials

• Shivaani Kummar, MD

  Oregon Health and Science University

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Dose Escalation: Seqeuntial Group Assignment, Dose Expansion: Parallel Group Assignment

Study Record Dates

• First Submitted: October 13, 2020
• First Posted: October 23, 2020
• Study Start: October 26, 2020
• Primary Completion: January 11, 2023
• Study Completion: January 11, 2023
• Last Updated: August 8, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)