Clinical trial NCT06082960: Study of GS-9911 With or Without Antibody Treatment for Adults With Solid Tumors
Official title: A Phase 1 Study to Evaluate the Safety and Tolerability of GS-9911 as Monotherapy and in Combination With an Anti-PD-1 Monoclonal Antibody in Adults With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Solid Tumors
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2023-10-13
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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


Eligibility 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/Exclusion criteria may apply.

Primary outcomes:
measure: Percentage of Participants With Treatment-emergent Adverse Events
timeFrame: First dose date up to 90 days post last dose (up to 105 weeks)
measure: Percentage of Participants With Treatment-emergent Serious Adverse Events
timeFrame: First dose date up to 90 days post last dose (up to 105 weeks)
measure: Percentage of Participants Experiencing any Dose-limiting Toxicities (DLTs) in Dose-escalation Cohorts
timeFrame: First dose date up to 3 weeks
Secondary outcomes:
measure: Plasma Concentration of GS-9911
timeFrame: Predose up to end of treatment (up to 105 weeks)
measure: Pharmacokinetic (PK) Parameter: Cmax of GS-9911
timeFrame: Predose up to end of treatment (up to 105 weeks)
measure: PK Parameter: Tmax of GS-9911
timeFrame: Predose up to end of treatment (up to 105 weeks)
measure: Area Under the Concentration-Time Curve (AUC) of GS-9911
timeFrame: Predose up to end of treatment (up to 105 weeks)
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Smilow Cancer Hospital Phase 1 Unit
state: Connecticut
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics, LLC
state: Texas
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Toronto
country: Canada
facility: University Health Network, Princess Margaret Cancer Centre
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: