Solid Tumor, Non Small Cell Lung Cancer, Squamous Cell Carcinoma of Head and Neck, Urothelial Carcinoma
Conditions
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.
Interventions
DRUGGEN-001
The capsules taken by mouth once a daily. Each capsule will contain ≥ 1x10\^11 colony-forming units (CFU)
DRUGAvelumab
800 mg given by intravenous (IV) infusion once every 2 weeks
Sponsors
Merck KGaA, Darmstadt, Germany
Pfizer
Genome & Company
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose Escalation: Seqeuntial Group Assignment, Dose Expansion: Parallel Group Assignment
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Escalation: Incidence of Laboratory abnormalities | 1 years | Assessed as per CTCAE v5.0 |
| Dose Expansion: To assess objective response (OR) of GEN-001 in patients with advanced or metastatic solid tumors, when administered as combined with avelumab. | 2 years | Confirmed OR per RECIST v1.1 by the Investigator |
| Dose Escalation: Incidence of dose-limiting toxicity (DLT) | 1 Cycle (one cycle = 28 days) | To evaluate the safety and tolerability of GEN-001 in combination with avelumab |
| Dose Escalation: Incidence of Adverse Events | 1 years | Assessed as per CTCAE v5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | up to 2 years | — |
| Incidence of Laboratory Abnormalities | up to 2 years | Assessed as per CTCAE v5.0 |
| irOR (Immune-related Objective Response) | up to 2 years | Assessed according to irRECIST |
| Incidence of Adverse Events | up to 2 years | Assessed as per CTCAE v5.0 |
| Objective Response (OR) | 1 years | Assessed according to RECIST v1.1 |
| Duration of response (DoR) | up to 2 years | Assessed according to RECIST v1.1 |
| Progression-free survival (PFS) | up to 2 years | Assessed according to RECIST v1.1 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Ctrough | up to 2 years | Ctrough for PK parameter |
| Microbiota | up to 2 years | fecal samples will be collected for analysis |
| ADA | up to 2 years | Anti-Drug Antibodies(ADA) for Immunogenicity |
Countries
United States
Outcome results
None listed