Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of GS-9716 as Monotherapy and in Combination With Anticancer Therapies in Adults With Solid Malignancies

  • STATUS
    Recruiting
  • End date
    May 3, 2028
  • participants needed
    205
  • sponsor
    Gilead Sciences
Updated on 3 July 2022

Summary

The primary objective of Part A of this study is to define the maximum tolerated dose (MTD) or maximum administered dose of GS-9716 as monotherapy in advanced solid malignancies and to characterize the safety, and tolerability of GS-9716 monotherapy.

The primary objectives of Parts B and C of this study are: To characterize the safety, tolerability, and to define MTD and/or recommended Phase 2 dose (RP2D) of GS-9716 in combination with either docetaxel or sacituzumab govitecan-hziy in adults with metastatic non-squamous non-small cell lung cancer (NSCLC) following treatment for metastatic disease, including an immune checkpoint inhibitor and a single line of platinum containing chemotherapy (for Cohorts B1, B2, C1, and C2) and in adults with metastatic triple-negative breast cancer (TNBC) following a single line of therapy for metastatic disease (for Cohorts B3, B4, C3, and C4); To characterize the safety, tolerability, and to define MTD and/or the RP2D of GS-9716 in combination with gemcitabine and docetaxel in metastatic soft tissue sarcomas (mSTS) with nonspecific histologies previously untreated for metastatic disease (for Cohorts B5 and C5).

Details
Condition Solid Malignancies
Treatment docetaxel, Gemcitabine, Sacituzumab Govitecan-hziy, GS-9716
Clinical Study IdentifierNCT05006794
SponsorGilead Sciences
Last Modified on3 July 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Part A: GS-9716 Monotherapy
Histologically or cytologically confirmed epithelial cancer, stage IV (metastatic) disease or locally advanced and unresectable (mixed histologies not permitted)
Breast cancer
Castrate-resistant prostate cancer not on hormonal androgen deprivation therapy
Cervical cancer
Colorectal cancer
Endometrial cancer
Epithelial ovarian cancer
Esophageal cancer
Follicular thyroid cancer
Gastric or gastroesophageal junction adenocarcinoma
Head and neck cancers- squamous cell carcinoma
Hepatocellular carcinoma
NSCLC
Renal cell cancer (clear cell)
Small-cell lung cancer
Urothelial cancer
Progressed after at least 1 prior standard therapeutic regimen, or for whom no
standard therapy is available, standard therapy has failed, or for whom
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as described in protocol
standard of care therapy is contraindicated
Adequate hematology, renal and hepatic function as described in the protocol
Tissue criteria: Individuals must have available, sufficient, and adequate formalin-fixed tumor tissue sample or must agree to have a biopsy taken prior to entering the study to provide adequate tissue. Core needle or excisional biopsy or resected tissue is required
All toxicity at screening ≤ Grade 1, including peripheral neuropathy and excluding alopecia of any grade, well-controlled endocrine toxicities from prior immune checkpoint inhibitor therapy ≤ Grade 2, and chronic electrolyte abnormalities requiring supplementation ≤ Grade 2
Part B and Part C: GS-9716 in Combination with Anticancer Therapies (All
Left ventricular ejection fraction (LVEF) ≥ 50% acquisition scan (MUGA) may be acceptable per discussion with the medical monitor
Cohorts)
ECOG performance status of 0 or 1
Adequate hematology, renal and hepatic function as described in the protocol
Tissue criteria
Otherwise, all toxicity at screening entry ≤ Grade 1, including peripheral neuropathy and excluding alopecia of any grade, well-controlled endocrine toxicities from prior immune checkpoint inhibitor therapy ≤ Grade 2, and chronic electrolyte abnormalities requiring supplementation ≤ Grade 2
LVEF ≥ 50%, as well as no clinically significant pericardial effusion
TNBC cohorts B3, C3, B4, C4: Individuals must have a tumor lesion that a mandatory pretreatment biopsy can be obtained from. Core needle, or excisional biopsy, or resected tissue is required. Fine needle aspirates and bone biopsies are not acceptable
Cohorts B1, C1, B2, C2, B5, C5: Individuals must have available, sufficient, and adequate formalin-fixed tumor tissue sample or must agree to have a biopsy taken prior to entering the study to provide adequate tissue. Core needle or excisional biopsy or resected tissue is required
Cohorts B1, B2, C1, and C2
Histologically or cytologically confirmed unresectable metastatic or locally advanced, non-squamous NSCLC following treatment for metastatic disease including an immune checkpoint inhibitor and a single line of platinum-containing chemotherapy
Individuals with bone metastases currently receiving bisphosphonates for palliation will be eligible providing informed consent can be given and that other qualifying sites of measurable disease are present
Cohorts B3, B4, C3, and C4
Histologically or cytologically confirmed TNBC based on the most recent analyzed biopsy or other pathology specimen. Triple-negative status for TNBC will be defined by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines (US sites) or their equivalent (ex-US sites)
Unresectable locally advanced or metastatic disease following only 1 prior standard therapeutic regimen for TNBC. Individuals who have received 2 or more prior systemic therapies are not eligible
Individuals with bone metastases currently receiving bisphosphonates for palliation
Individuals with stable, treated brain metastases will be eligible
Cohorts B5 and C5
Histologically proven soft tissue sarcoma (except the following histologies: gastrointestinal stromal tumors [GIST], Kaposi's sarcoma, mesotheliomas) which has been previously untreated for metastatic disease

Exclusion Criteria

Prior treatment with any myeloid cell leukemia 1 (MCL1) inhibitor
Prior radiotherapy (or other nonsystemic therapy) within 2 weeks prior to dosing with GS-9716
Treatment with any high dose systemic corticosteroids within 2 weeks of the first dose of GS-9716. However, low dose corticosteroids ≤ 10 mg prednisone or equivalent daily is permitted
Women who are pregnant or lactating
Individuals with brain metastases may be enrolled only if treated, nonprogressive, and asymptomatic as well as off high dose steroids (> 10 mg prednisone or equivalent) for at least 4 weeks prior to dosing with GS-9716
History of leptomeningeal disease
Known active or chronic hepatitis B or C infection or HIV infection or HIV positive
Individuals with active ≥ Grade 2 nausea or vomiting, and/or signs of intestinal obstruction
Known history of unstable angina, myocardial infarction (MI), cardiac angioplasty or stenting, or clinically significant cardiac disease would include QTc interval > 450 ms for males and > 470 ms for females
Known history of clinically significant active chronic obstructive pulmonary disease (COPD), or other moderate to severe chronic respiratory illness present within 6 months prior to dosing with GS-9716
Known history of clinically significant pulmonary interstitial lung disease, active interstitial lung disease, idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (more frequently than once monthly)
Prior history of clinically significant bleeding, intestinal obstruction, or gastrointestinal (GI) perforation within 6 months of initiation of study treatment
Infection requiring intravenous anti-infective use within 2 weeks prior to dosing with GS-9716
Active or history of autoimmune disease or immune deficiency
History of uncured coexisting cancer, not including uncured basal cell carcinoma, cervical cancer in situ, or superficial bladder cancer
Cohorts B1, B3, B5, C1, C3, and C5
Bilirubin > upper limit of normal (ULN)
Cohorts B1, B2, C1, and C2
More than 1 prior chemotherapy regimen for metastatic non-squamous NSCLC; however, this would not exclude those who received frontline immune checkpoint inhibitor as monotherapy followed by a platinum-containing chemotherapeutic regimen in the second line
Non-squamous NSCLC with targetable mutations (e.g., anaplastic lymphoma kinase [ALK], epidermal growth factor receptor [EGFR], proto-oncogene tyrosine-protein kinase ROS [ROS1], v-RAF murine sarcoma viral oncogene homolog B [BRAF]) for which approved therapies are available
Cohorts B2 and C2 only: Prior therapy with sacituzumab govitecan-hziy or a topoisomerase 1 inhibitor or agents targeting Trop-2
Cohorts B3, B4, C3, and C4
More than 1 prior chemotherapy regimen for metastatic TNBC
Cohorts B4 and C4 only: Prior treatment with sacituzumab govitecan-hziy or a topoisomerase 1 inhibitor or agents targeting Trop-2
Cohorts B5 and C5
Any previous treatment for metastatic disease
Soft tissue sarcomas with the following histologies: GIST, Kaposi's sarcoma, or mesotheliomas
Note: Other protocol defined Inclusion/Exclusion criteria may apply
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