Clinical trial NCT06167317: Study of GS-0201 Alone and in Combination in Participants With Advanced Solid Tumors
Official title: A Phase 1 Study to Evaluate the Safety and Tolerability of GS-0201 as Monotherapy and in Combination in Adults With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2023-12-12
Enrollment: 254
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-0201 when given alone or in combination with sacituzumab govitecan (SG) in participants with advanced solid tumors.

The primary objectives of this study are to:

* To assess the safety and tolerability of GS-0201 as monotherapy and in combination with SG in participants with selected advanced solid tumors
* To identify the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of GS-0201 as monotherapy and the MTD and/or the RP2D and dosing schedule of GS-0201 in combination with SG in participants with selected advanced solid tumors


Eligibility criteria: Inclusion Criteria:

* Able to understand and give written informed consent.
* Assigned female or male at birth, 18 years of age or older.
* Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
* Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria by investigator assessment.
* Organ function requirements:

  * Adequate hematologic function
  * Adequate hepatic function
  * Creatinine clearance
  * Coagulation
* Tissue requirement:

  * Parts A, B, C, and D:

    * Pre-treatment tumor tissue is required.
  * Parts A and C backfill biopsy cohorts:

    * Participants must agree to fresh pre- and on-treatment biopsies.
* Participants assigned male at birth and participants assigned female at birth and of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception
* Willing and able to comply with the requirements and restrictions in this protocol
* Part A (GS-0201 Monotherapy Dose Escalation) Inclusion Criteria:

  * Histologically/cytologically confirmed progressive/advanced solid tumors with selected molecular lesions.
  * Participants must have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit or have a contraindication to receive the therapy
* Part B (Dose Expansion) Inclusion Criteria:

  * Disease documented as:
  * Cohort B1:

    * Histologically or cytologically confirmed progressive/advanced selected solid tumor diagnoses harboring defined molecular lesions
    * Participants may potentially be required to forgo treatment with approved agent(s) to be able to participate in the study
  * Cohort B2:

    * Histologically or cytologically confirmed progressive/advanced solid tumor diagnoses harboring defined molecular lesions not included in Cohort B1
    * Participants must have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit or have a contraindication to receive the therapy
* Part C (Dose Escalation) Inclusion Criteria:

  * Histologically or cytologically confirmed unresectable locally advanced/metastatic selected solid tumors
* Part D (Dose Expansion) Inclusion Criteria:

  * Disease documented as:
  * Cohort D1:

    * Histologically or cytologically confirmed unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC)
  * Cohort D2:

    * Histologically or cytologically confirmed unresectable locally advanced or metastatic HR+/HER2- (IHC 0, IHC 1+ or IHC 2+/ in situ hybridization (ISH-)) breast cancer.

Exclusion Criteria:

* Pregnant or lactating females
* Known hypersensitivity to any of the study drugs, its metabolites, or formulation excipients
* Requirement for ongoing therapy with or use of any prohibited medications described in the protocol
* Participants with myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with findings suggestive of MDS/AML
* Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of GS-0201
* The therapies listed below within the specified timeframe:

  * Major surgery (excluding minor procedures, eg, placement of vascular access, gastrointestinal/biliary stent, biopsy) \< 4 weeks prior to planned Cycle 1 Day 1
  * Immunotherapy or biologic therapy \< 21 days prior to planned Cycle 1 Day 1
  * Chemotherapy \< 14 days prior to planned Cycle 1 Day 1, or \< 42 days for mitomycin or nitrosoureas
  * Targeted small molecule therapy \< 14 days prior to planned Cycle 1 Day 1
  * Receipt of experimental therapy within 21 days or 5 experimental treatment half-lives (whichever is longer) prior to planned Cycle 1 Day 1
  * Hormonal or other adjunctive therapy for cancers other than the cancer under evaluation in this study that started \< 14 days prior to planned Cycle 1 Day 1 are not permitted. Hormonal therapy, bisphosphonates, somatostatin analogues, and leuprolide are permitted if started ≥ 14 days prior to planned Cycle 1 Day 1
  * Radiotherapy within 2 weeks prior to planned Cycle 1 Day 1 and the radiation is not administered to a target lesion
  * Any prior allogeneic tissue/solid organ transplantation, including allogeneic hematopoietic stem cell transplantation. Participants with a history of autologous hematopoietic stem cell transplantation are also excluded
* Have not recovered (ie, Grade 1 or lower) from AEs due to a previously administered agent
* Prior treatment with approved or experimental prohibited agents as detailed in the protocol.
* Diagnosis of immunodeficiency, either primary or acquired, or requires systemic corticosteroids (\> 10 mg of prednisone daily, or equivalent). However, replacement doses, topical, ophthalmologic, and inhalational steroids are permitted
* Have an active second malignancy
* Have known active central nervous system (CNS) metastases
* Participants with carcinomatous meningitis or primary CNS tumors are excluded regardless of clinical stability
* Meet any of the following criteria for cardiac disease:

  * Myocardial infarction or unstable angina pectoris within 6 months of enrollment
  * History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication)
  * QT interval \> 470 msec
  * New York Heart Association Class III or greater congestive heart failure or known left ventricular ejection fraction less than 40%
* Meet any of the following infectious criteria:

  * Have active serious infection requiring antimicrobials
  * Have active hepatitis B virus (HBV) or hepatitis C virus (HCV), or HIV. In participants with a history of HBV or HCV, participants with detectable viral loads will be excluded
  * Participants who test positive for hepatitis B surface antigen. Participants who test positive for hepatitis B core antibody are eligible with a negative HBV DNA by quantitative Polymerase chain reaction (PCR)
  * Participants who test positive for HCV antibody. Participants who test positive for HCV antibody are eligible with a negative HCV RNA by quantitative PCR
  * Participants who test positive for HIV antibody
* History of pneumonitis requiring treatment with corticosteroids, interstitial lung disease, or radiation pneumonitis requiring steroids
* Symptomatic ascites or pleural effusion
* Have other concurrent medical or psychiatric conditions that, in the investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations
* Any medical condition that, in the investigator's or sponsor's opinion, poses an undue risk to the participant's participation in the study
* Use of any live vaccines against infectious diseases within 4 weeks (28 days) of initiation of study drug(s) (inactivated, viral vector vaccines, and messenger RNA (mRNA) vaccines are allowed; seasonal vaccines should be up to date prior to planned Cycle 1 Day 1)
* Parts C (Dose Escalation) and D (Dose Expansion): Combination Cohorts:

  * Participants with active chronic inflammatory bowel disease (ulcerative colitis, Crohn disease) and participants with a history of bowel obstruction or gastrointestinal perforation within 6 months prior to planned Cycle 1 Day 1
  * Participants who previously received topoisomerase 1 inhibitors or antibody-drug conjugates containing a topoisomerase 1 inhibitor
  * Known severe intolerance or life-threatening hypersensitivity reactions to humanized monoclonal antibodies or intravenous (IV) immunoglobulin preparations; any history of anaphylaxis; history of human anti-human antibody response

Primary outcomes:
measure: The Number of Participants with Dose Limiting Toxicities (DLTs) During Dose Escalation
timeFrame: First dose up to 30 days post last dose (Up to approximately 109 weeks).
measure: The Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: First dose up to 30 days post last dose (Up to approximately 109 weeks).
measure: The Incidence of Laboratory Abnormalities
timeFrame: First dose up to 30 days post last dose (Up to approximately 109 weeks).
Secondary outcomes:
measure: Pharmacokinetic (PK) Parameter: Area Under the Concentration (AUC)0-24 of GS-0201
timeFrame: Predose and postdose up to end of treatment (up to 105 weeks)
measure: PK Parameter: Cmax of GS-0201
timeFrame: Predose and postdose up to end of treatment (up to 105 weeks)
measure: PK Parameter: Tmax of GS-0201
timeFrame: Predose and postdose up to end of treatment (up to 105 weeks)
measure: PK Parameter: AUC0-168 of SG (Parts C and D only)
timeFrame: Predose and postdose up to end of treatment (up to 105 weeks)
measure: PK Parameter: Cmax of SG (Parts C and D only)
timeFrame: Predose and postdose up to end of treatment (up to 105 weeks)
measure: PK Parameter: Tmax of SG (Parts C and D only)
timeFrame: Predose and postdose up to end of treatment (up to 105 weeks)
measure: GS-0201 Plasma Concentrations
timeFrame: Predose and postdose up to end of treatment (up to 105 weeks)
measure: Sacituzumab Govitecan (SG) Serum Concentrations (Parts C and D only)
timeFrame: Predose and postdose up to end of treatment (up to 105 weeks)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Austin
country: United States
facility: NEXT Austin
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Irving
country: United States
facility: NEXT Dallas
state: Texas
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Tel Hashomer
country: Israel
facility: Chaim Sheba Medical Center
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: