Clinical trial NCT04747470: Study to Assess the Effects of GS-3583 in Participants With Advanced Solid Tumors
Official title: A Phase 1b Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of GS-3583, a FLT3 Agonist Fc Fusion Protein, in Subjects With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2021-02-10
Enrollment: 13
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: This study is planned to be conducted in 2 parts: Part 1: Dose Escalation and Part 2: Safety Run-In and Randomized Expansion.

The primary objectives of Part 1 are 1) To characterize the safety and tolerability of GS-3583 as monotherapy in participants with advanced solid tumors. 2) To determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of GS-3583 as monotherapy in participants with advanced solid tumors.

The primary objectives of Part 2 is to assess the safety and tolerability and to determine the RP2D of GS-3583 in combination with zimberelimab (ZIM) and platinum (cisplatin or carboplatin) + 5-fluorouracil (5-FU) chemotherapy in participants with head and neck squamous cell carcinoma (HNSCC) (Cohort A) or in combination with docetaxel in participants with non-small cell lung cancer (NSCLC) (Cohort B).


Eligibility criteria: Key Inclusion Criteria:

* Histologically or cytologically confirmed locally advanced or metastatic malignant solid tumor that is refractory to or intolerant of standard therapy or for which no standard therapy is available
* Have measurable disease on imaging based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
* Eastern Cooperative oncology Group (ECOG) performance status of ≤ 2
* Life expectancy of ≥ 3 months, in the opinion of the investigator
* Adequate organ function as assessed by hematological, renal, and hepatic parameters, and no clinically significant coagulopathy

Key Exclusion Criteria:

* Received prior systemic cytotoxic chemotherapy, biological therapy, radiotherapy, or major surgery within 3 weeks of Cycle 1 Day 1; a 1-week washout is permitted for palliative radiation to non-central nervous system (CNS) disease with sponsor approval
* Known severe hypersensitivity reactions (NCI CTCAE Grade ≥ 3) to fully human monoclonal antibodies or fusion proteins, GS-3583 formulation excipients, or severe reaction to immuno-oncology agents, such as colitis or pneumonitis requiring treatment with corticosteroids, any history of anaphylaxis, or uncontrolled asthma
* Concurrent active malignancy other than nonmelanoma skin cancer, carcinoma in situ of the cervix, or superficial bladder cancer who has undergone potentially curative therapy with no evidence of disease. Individuals with other previous malignancies are eligible if disease free for \> 2 years.
* Previous history of hematological malignancy, monoclonal gammopathy of unknown significance (MGUS) or other preleukemic states (Presence of clonal hematopoiesis of indeterminate potential (CHIP)/age related clonal hematopoiesis (ARCH) is acceptable)
* Known CNS metastasis(es), unless metastases are treated and stable and the individual does not require systemic corticosteroids for management of CNS symptoms at least 1 week prior to study treatment. Individuals with history of carcinomatous meningitis are excluded regardless of clinical stability.
* Active or history of autoimmune disease that has required systemic treatment within 2 years of the start of study treatment (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs)

  * Note: Individuals with diabetes type 1, vitiligo, psoriasis, hypothyroid disease, or hyperthyroid disease, not requiring immunosuppressive treatment are eligible.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Parts 1 and 2: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)
timeFrame: Part 1: Day 1 through Day 28; Part 2: Day 1 through Day 21
measure: Parts 1 and 2: Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
timeFrame: First dose date up to last dose date plus 90 days (Up to 4 months)
measure: Parts 1 and 2: Percentage of Participants With Laboratory Abnormalities According to the NCI CTCAE Version 5.0
timeFrame: First dose date up to last dose date plus 90 days (Up to 4 months)
measure: Parts 1 and 2: Percentage of Participants With GS-3583 Anti-drug Antibodies (ADAs) at Any Visit
timeFrame: Cycles 1and 3,pre-dose,End of Infusion (EOI);2,6 hours;Days 2,3,5,8,15 post Day 1EOI;Day 15:Cycle 1:predose and EOI;2 hours post EOI;Cycle 3:336 hours and Day 24 post EOI(Cycle length = 28 days in Part 1; 21 days for Part 2;infusion duration=60 minutes)
Secondary outcomes:
measure: Part 1: Pharmacokinetic (PK) Parameter: AUCtau of GS-3583
timeFrame: Cycles 1 and 3, pre-dose, EOI; 2, 6 hours; Days 2, 3, 5, 8, 15 post Day 1 EOI; Day 15:Cycle 1:predose and EOI; 2 hours post EOI;Cycle 3:336 hours and Day 24 post EOI (Cycle length for all cycles=28 days in Part 1; Infusion duration=60 minutes)
measure: Part 1: PK Parameter: Cmax of GS-3583
timeFrame: Cycles 1 and 3,pre-dose,EOI;2, 6 hours;Days 2, 3, 5, 8, 15 post Day 1 EOI;Day 15:Cycle 1:predose and EOI;2 hours post EOI;Cycle 3:336 hours and Day 24 post EOI (Cycle length for all cycles=28 days in Part 1;Infusion duration=60 minutes)
measure: Part 1: PK Parameter: Tmax of GS-3583
timeFrame: Cycles 1 and 3, pre-dose, EOI; 2, 6 hours; Days 2, 3, 5, 8, 15 post Day 1 EOI; Day 15:Cycle 1:predose and EOI; 2 hours post EOI; Cycle 3:336 hours and Day 24 post EOI (Cycle length for all cycles=28 days in Part 1; infusion duration=60 minutes)
measure: Part 2: Confirmed Objective Response Rate (ORR)
timeFrame: First dose date in Part 2 to End of Study (approximately 4.2 months)
measure: Part 2: Progression-free Survival (PFS)
timeFrame: First dose date in Part 2 to End of Study (approximately 4.2 months)
measure: Part 2: Duration of Response (DOR)
timeFrame: First dose date in Part 2 to End of Study (approximately 4.2 months)
measure: Part 2: Overall Survival (OS)
timeFrame: First dose date in Part 2 to End of Study (approximately 4.2 months)
measure: Part 2: Disease Control Rate (DCR)
timeFrame: First dose date in Part 2 to End of Study (approximately 4.2 months)
measure: Part 2: PK Parameters: Cmax for GS-3583
timeFrame: Safety-run In:Cycles 1 and 3: Day 1, predose, EOI; 2, 6 hours, Days 8, 15; Part 2 all arms:Cycles 2 and 5: Day 1 predose, EOI and every odd cycles; 60-day FU; (Cycle length of all cycles = 21 days in Part 2; Infusion duration=60 minutes)
measure: Part 2: PK Parameter: Tmax for GS-3583
timeFrame: Safety-run In: Cycles 1, and 3: Day 1, predose, EOI; 2, 6 hours, Days 8, Day 15; Part 2: all arms: Cycles 2 and 5: Day 1 predose, EOI and every odd cycles; 6-day FU; (Cycle length of all cycles = 21 days in Part 2; Infusion duration=60 minutes)
measure: Part 2: PK Parameter: AUCtau of GS-3583
timeFrame: Safety-run In: Cycles 1, and 3: Day 1, predose, EOI; 2, 6 hours, Days 8, Day 15; Part 2: all arms: Cycles 2 and 5: Day 1 predose, EOI and every odd cycles; 6-day FU; (Cycle length of all cycles = 21 days in Part 2; Infusion duration=60 minutes)
Other outcomes:
Locations:
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: San Antonio
country: United States
facility: NEXT oncology
state: Texas
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Brody J, Thompson JA, Tolcher AW, Kuhne MR, Huang XR, et al. Phase 1b Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of GS3583, a FLT3 Agonist Fc Fusion Protein, in Patients With Advanced Solid Tumors [Poster TPS3147]. J Clin oncol 2021 June; 39 (15_suppl).
citation: Tolcher AW, Brody J, Rajakumaraswamy N, Lakhani NJ, Kuhne MR, Trowe T, et al. Phase 1b study of GS-3583, a novel FLT3 agonist Fc fusion protein, in patients with advanced solid tumors. [Poster TPS2566]. J Clin oncol 2022 June; 40 (16_suppl).
citation: Dauki AM, Jones A, Singh I, Rajakumaraswamy N, Qin A, et al. Population pharmacokinetics of GS-3583 in healthy volunteers and patients with advanced solid tumors [Poster II-083]. Clin Pharmacol Ther 2023 March; 113 (S5-S100).