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

Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04601402
• Other study ID #: [GNC] GEN001-101
• Status: Completed
• Phase: Phase 1
• Start date: October 26, 2020
• Est. completion date: January 11, 2023

Study information

• Verified date: June 2023
• Source: Genome & Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: January 11, 2023
• Est. primary completion date: January 11, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• GEN-001
The capsules taken by mouth once a daily. Each capsule will contain = 1x10^11 colony-forming units (CFU)
• Avelumab
800 mg given by intravenous (IV) infusion once every 2 weeks

Locations

Country	Name	City	State
United States	Emory University Winship Cancer Institute	Atlanta	Georgia
United States	Yale Cancer Center	New Haven	Connecticut
United States	Oregon Health & Science University	Portland	Oregon

Sponsors (3)

Lead Sponsor	Collaborator
Genome & Company	Merck KGaA, Darmstadt, Germany, Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Ctrough	Ctrough for PK parameter	up to 2 years
Other	ADA	Anti-Drug Antibodies(ADA) for Immunogenicity	up to 2 years
Other	Microbiota	fecal samples will be collected for analysis	up to 2 years
Primary	Dose Escalation: Incidence of Adverse Events	Assessed as per CTCAE v5.0	1 years
Primary	Dose Escalation: Incidence of Laboratory abnormalities	Assessed as per CTCAE v5.0	1 years
Primary	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)
Primary	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	Objective Response (OR)	Assessed according to RECIST v1.1	1 years
Secondary	Duration of response (DoR)	Assessed according to RECIST v1.1	up to 2 years
Secondary	Progression-free survival (PFS)	Assessed according to RECIST v1.1	up to 2 years
Secondary	Overall Survival (OS)		up to 2 years
Secondary	Incidence of Adverse Events	Assessed as per CTCAE v5.0	up to 2 years
Secondary	Incidence of Laboratory Abnormalities	Assessed as per CTCAE v5.0	up to 2 years
Secondary	irOR (Immune-related Objective Response)	Assessed according to irRECIST	up to 2 years