Active, not recruiting
Phase 1
Study of GS-4528 in Adults With Solid Tumors
Condition(s) studied
Solid Tumor
Investigational drug(s) / intervention(s)
GS-4528: Administered intravenously
Zimberelimab: Administered intravenously.
Study summary
The goals of this clinical study are to identify if GS-4528 alone or in combination with anti-programmed cell death protein 1 (PD-1) (Anti-PD-1) Monoclonal Antibody is safe and tolerable in people with solid tumors and to identify the recommended dose of GS-4528 for further development that is safe to give to people alone or in combination with Anti-PD-1 Monoclonal Antibody.
The primary objectives of this study are:
* To assess the safety and tolerability of GS-4528 as monotherapy and in combination with Anti-PD-1 Monoclonal Antibody in participants with advanced solid tumors.
* To identify the maximum tolerated dose (MTD)/maximum administered dose (MAD) and/or the recommended Phase 2 dose (RP2D) of GS-4528 as monotherapy and in combination with Anti-PD-1 Monoclonal Antibody in participants with advanced solid tumors.
Eligibility
Key Inclusion Criteria:
* Documented disease:
* Phase 1a dose escalation and backfill cohorts; Phase 1b dose escalation: Individuals with histologically or cytologically confirmed advanced solid tumors who have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit or have a contraindication to receive the therapy.
* Phase 1a dose expansion: Individuals with histologically or cytologically confirmed select indications who have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit or have a contraindication to receive the therapy.
* Eastern Cooperative Oncology Group performance status 0 or 1.
* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
* Adequate organ function.
* Individuals of childbearing potential who engage in heterosexual intercourse must agree to use method(s) of contraception.
* Tissue requirements:
* Phase 1a dose escalation, Phase 1a dose expansion, and Phase 1b dose escalation: Must provide pre-treatment adequate tumor tissue sample prior to enrolment.
* Phase 1a backfill cohorts: Individuals must have fresh pre-treatment and on-treatment biopsy for biomarker analysis.
* Life expectancy ≥ 3 months.
Key Exclusion Criteria:
* Positive serum pregnancy test or lactating female.
* Prohibited concurrent anticancer therapy listed in the protocol.
* Any anti-cancer therapy, whether investigational or approved, within protocol specified time prior to initiation of study including: major surgery (\<28 days), immunotherapy or biologic therapy (\< 28 days), chemotherapy (\< 21 days), targeted small molecule therapy (\< 14 days or \< 5 half-lives whichever is shorter), hormonal therapy or other adjunctive therapy (\< 14 days) or radiotherapy (\< 21 days).
* Any prior allogeneic tissue/solid organ transplantation, including allogeneic stem cell transplantation.
* Diagnosis of immunodeficiency, either primary or acquired, or systemic steroid requirement of \> 10 mg of prednisone or equivalent.
* History of intolerance, hypersensitivity, or treatment discontinuation due to severe immune-related adverse events (irAEs) on prior immunotherapy.
* History of autoimmune disease or active autoimmune disease that has required systemic treatment within 2 years prior to the start of study treatment.
* Concurrent active second malignancy. Note: Individuals with a history of malignancy that have been completely treated, with no evidence of active cancer for 2 years prior to enrollment, or participants with surgically cured tumors with low risk of recurrence are allowed to enroll.
* Have known active central nervous system (CNS) metastases and/ or carcinomatous meningitis.
* Significant cardiovascular disease.
* Have active serious infection requiring antibiotics.
* Have active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV).
* History of pneumonitis, interstitial lung disease, or severe radiation pneumonitis (excluding localized radiation pneumonitis).
* Symptomatic ascites or pleural effusion.
* Live vaccines within 28 days of initiation of investigational product(s).
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Primary outcome measure(s)
- Percentage of Participants Experiencing Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) — First dose date up to 90 days post last dose (Up to 24 months)
- Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) — Day 1 up to 4 weeks
- Maximum Tolerable Dose (MTD) of GS-4528 — Day 1 up to 4 weeks
Trial sites (16)
| Facility | City | Region | Status |
| The University of Washington/FHCC |
Seattle |
Washington |
|
| The Ottawa Hospital |
Ottawa |
Canada |
|
| University Health Network, Princess Margaret Cancer Centre |
Toronto |
Canada |
|
| Asan Medical Center |
Seoul |
South Korea |
|
| Severance Hospital, Yonsei University Health Systems |
Seoul |
South Korea |
|
| Samsung Medical Center |
Seoul |
South Korea |
|
| NEXT Oncology-Hospital Quironsalud Barcelona - Unidad de Ensayos Fase 1 |
Barcelona |
Spain |
|
| Hospital Universitari Vall D'Hebron- Oncology Service |
Barcelona |
Spain |
|
| START MADRID_Hospital Universitario Fundacion Jimenez Diaz - Unidad de Ensayos Fases I |
Madrid |
Spain |
|
| START MADRID_HM Sanchinarro-CIOCC-Unidad de Ensayos Fases I |
Madrid |
Spain |
|
| Clinica Universidad de Navarra- Unidad Central de Ensayos Clinicos |
Pamplona |
Spain |
|
| Taichung Veterans General Hospital |
Taichung |
Taiwan |
|
| National Taiwan University Hospital |
Taipei |
Taiwan |
|
| Chang Gung Memorial Hospital Linkuo Branch of the Chang Gung Medical Foundation |
Taoyuan |
Taiwan |
|
| St Bartholomew's Hospital |
London |
United Kingdom |
|
| The Royal Marsden NHS Foundation Trust |
Sutton |
United Kingdom |
|
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