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

A Phase I/Ib Study to Evaluate the Safety, Tolerability, Biological and Clinical Activities of GEN-001 in Combination With Avelumab in Patients With Advanced Solid Tumors Who Have Progressed During or After Treatment With Anti-PD-(L)1 Therapy

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.

Study Overview

• Status: Completed
• Conditions: Solid Tumor; Non Small Cell Lung Cancer; Squamous Cell Carcinoma of Head and Neck; Urothelial Carcinoma
• Intervention / Treatment: Drug: Avelumab; Drug: GEN-001

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Winship Cancer Institute
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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)

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: GEN-001 with avelumab; 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: Avelumab; 800 mg given by intravenous (IV) infusion once every 2 weeks; Other Names: Bavencio; Drug: GEN-001; The capsules taken by mouth once a daily. Each capsule will contain ≥ 1x10^11 colony-forming units (CFU)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)		up to 2 years
Objective Response (OR)	Assessed according to RECIST v1.1	1 years
Duration of response (DoR)	Assessed according to RECIST v1.1	up to 2 years
Progression-free survival (PFS)	Assessed according to RECIST v1.1	up to 2 years
Incidence of Adverse Events	Assessed as per CTCAE v5.0	up to 2 years
Incidence of Laboratory Abnormalities	Assessed as per CTCAE v5.0	up to 2 years
irOR (Immune-related Objective Response)	Assessed according to irRECIST	up to 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ctrough	Ctrough for PK parameter	up to 2 years
ADA	Anti-Drug Antibodies(ADA) for Immunogenicity	up to 2 years
Microbiota	fecal samples will be collected for analysis	up to 2 years

Collaborators and Investigators

• Sponsor: Genome & Company
• Collaborators: Pfizer; Merck KGaA, Darmstadt, Germany
• Investigators: Principal Investigator: Shivaani Kummar, MD, Oregon Health and Science University

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2020
• Primary Completion (Actual): January 11, 2023
• Study Completion (Actual): January 11, 2023

Study Registration Dates

• First Submitted: October 13, 2020
• First Submitted That Met QC Criteria: October 19, 2020
• First Posted (Actual): October 23, 2020

Study Record Updates

• Last Update Posted (Actual): August 8, 2023
• Last Update Submitted That Met QC Criteria: August 6, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Squamous Cell Carcinoma of Head and Neck; Antineoplastic Agents; Antineoplastic Agents, Immunological; Avelumab
• Other Study ID Numbers: [GNC] GEN001-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No