Solid Tumors
Conditions
Brief summary
The main goal of this first in human (FIH) study is to learn about the safety and dosing of GS-9911 when given alone or in combination with an anti-programmed cell death protein 1 (PD-1) monoclonal antibody in participants with advanced solid tumors. The primary objectives of this study are to: * Assess the safety and tolerability of GS-9911 as monotherapy and in combination with an anti-PD-1 monoclonal antibody in participants with advanced solid tumors * Identify the maximum tolerated dose (MTD)/maximum administered dose (MAD) and the recommended dose for expansion (RDE) of GS-9911 as monotherapy and in combination with an anti-PD-1 monoclonal antibody in participants with advanced solid tumors
Interventions
DRUGGS-9911
Tablets administered orally
DRUGZimberelimab
Administered intravenously
Sponsors
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Parts A, C, and D: * Participants with histologically or cytologically confirmed advanced solid tumors who have received, been intolerant to, or are ineligible for all treatments known to confer clinical benefit * Part B: * Participants whose cancer previously derived clinical benefit from immune checkpoint inhibitors, or who have advanced solid tumor types for which immune checkpoint inhibitors are considered the standard of care and who have received, been intolerant to, or are ineligible for all treatments known to confer clinical benefit * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Evaluable (Part A) or measurable (Parts B, C, and D) disease as per Response Criteria Evaluation in Solid Tumors (RECIST) v1.1 criteria * Adequate organ functions * Tissue requirement: * Parts A-D: must be willing to provide baseline tumor tissue prior to enrollment * Part A backfill cohorts: a biopsy should be obtained prior to treatment and on treatment, if safely feasible * Participants of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified methods of contraception
Exclusion criteria
* Positive serum pregnancy test or lactating female * History of intolerance, hypersensitivity, or treatment discontinuation due to life- threatening immune-related adverse events on prior immunotherapy * Receipt of the therapies listed below within the specified timeframe prior to planned Cycle 1 Day 1 including: major surgery (\< 4 weeks), immunotherapy or biologic therapy (\< 28 days), chemotherapy (\< 21 days), targeted small molecule therapy (\<14 days or 5 half-lives, whichever is sooner), hormonal or other adjunctive therapy (\< 14 days), radiation therapy (\< 21 days), live vaccine (\< 28 days) * Any prior allogeneic tissue/solid organ transplantation, including allogeneic stem cell transplantation * Diagnosis of immunodeficiency, or requires systemic corticosteroids (\> 10 mg of prednisone daily, or equivalent) * History of autoimmune disease or active autoimmune disease that has required systemic treatment within 2 years prior to the start of study drug * History of pneumonitis requiring treatment with corticosteroids, interstitial lung disease, drug-induced pneumonitis, or severe radiation pneumonitis (excluding localized radiation pneumonitis) * Active second malignancy. Note: individuals with a history of malignancy that have been completed treated, with no evidence of active cancer for 2 years prior to enrollment, or individuals with surgically cured tumors with low risk of recurrence are allowed to enroll. * Known active central nervous system (CNS) metastases and/or carcinomatous meningitis * Symptomatic cardiovascular disease * Active serious infection requiring ongoing treatment * Active infection with hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV. * Symptomatic ascites or pleural effusion Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Treatment-emergent Adverse Events | First dose date up to 90 days post last dose (up to 105 weeks) |
| Percentage of Participants With Treatment-emergent Serious Adverse Events | First dose date up to 90 days post last dose (up to 105 weeks) |
| Percentage of Participants Experiencing any Dose-limiting Toxicities (DLTs) in Dose-escalation Cohorts | First dose date up to 3 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Concentration of GS-9911 | Predose up to end of treatment (up to 105 weeks) | — |
| Pharmacokinetic (PK) Parameter: Cmax of GS-9911 | Predose up to end of treatment (up to 105 weeks) | Cmax is defined the maximum observed plasma drug concentration. |
| PK Parameter: Tmax of GS-9911 | Predose up to end of treatment (up to 105 weeks) | Tmax is defined as the time to maximum observed concentration. |
| Area Under the Concentration-Time Curve (AUC) of GS-9911 | Predose up to end of treatment (up to 105 weeks) | AUC is defined as the area under the concentration versus time curve. |
Countries
Australia, Canada, United States
Contacts
STUDY_DIRECTORGilead Study Director
Gilead Sciences
Outcome results
None listed