Clinical trial NCT04601402: GEN-001 (Live Biotherapeutic Product) and Avelumab Combination Study for Patients With Solid Tumors Who Have Progressed on Anti-PD-(L)1 Therapy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor
Non Small Cell Lung Cancer
Squamous Cell Carcinoma of Head and Neck
Urothelial Carcinoma
Lead sponsor: Genome & Company
Sponsor class: INDUSTRY
Collaborators: name: Merck KGaA, Darmstadt, Germany
name: Pfizer
First posted: 2020-10-23
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Dose Escalation: Seqeuntial Group Assignment, Dose Expansion: Parallel Group Assignment
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Dose Escalation: Incidence of Adverse Events
timeFrame: 1 years
measure: Dose Escalation: Incidence of Laboratory abnormalities
timeFrame: 1 years
measure: Dose Escalation: Incidence of dose-limiting toxicity (DLT)
timeFrame: 1 Cycle (one cycle = 28 days)
measure: Dose Expansion: To assess objective response (OR) of GEN-001 in patients with advanced or metastatic solid tumors, when administered as combined with avelumab.
timeFrame: 2 years
Secondary outcomes:
measure: Objective Response (OR)
timeFrame: 1 years
measure: Duration of response (DoR)
timeFrame: up to 2 years
measure: Progression-free survival (PFS)
timeFrame: up to 2 years
measure: Overall Survival (OS)
timeFrame: up to 2 years
measure: Incidence of Adverse Events
timeFrame: up to 2 years
measure: Incidence of Laboratory Abnormalities
timeFrame: up to 2 years
measure: irOR (Immune-related Objective Response)
timeFrame: up to 2 years
Other outcomes:
measure: Ctrough
timeFrame: up to 2 years
measure: ADA
timeFrame: up to 2 years
measure: Microbiota
timeFrame: up to 2 years
Locations:
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Atlanta
country: United States
facility: Emory University Winship Cancer Institute
state: Georgia
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
Study officials:
affiliation: Oregon Health and Science University
name: Shivaani Kummar, MD
role: PRINCIPAL_INVESTIGATOR
References: