Clinical trial NCT03954704: Study of Dalutrafusp Alfa (Formerly GS-1423) in Participants With Advanced Solid Tumors
Official title: A Phase 1a/1b Study of GS-1423, an Anti-CD73-TGFβ-Trap Bifunctional Antibody, as Monotherapy or in Combination With a Chemotherapy Regimen 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: 2019-05-17
Enrollment: 22
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: For Phase 1a Part A, the primary objectives are to assess safety and tolerability and to define the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of dalutrafusp alfa (formerly GS-1423) monotherapy in participants with advanced solid tumors.

For Phase 1a Part B, the primary objective is to assess safety and tolerability of dalutrafusp alfa monotherapy in participants with advanced solid tumors.

For Phase 1b Cohort 1 safety run-in, the primary objective is to assess safety and tolerability and to define the DLT and MTD or RP2D of dalutrafusp alfa in combination with a chemotherapy regimen in participants with advanced gastric or gastroesophageal junction adenocarcinoma.

For Phase 1b Cohort 1 post safety run-in, the primary objective is to assess the preliminary efficacy of dalutrafusp alfa in combination with a chemotherapy regimen in participants with advanced gastric or gastroesophageal junction adenocarcinoma, as assessed by the confirmed objective response rate (ORR).

For Phase 1b Cohort 2, the primary objective is to assess safety and tolerability of dalutrafusp alfa monotherapy in participants with advanced solid tumors.


Eligibility criteria: Key Inclusion Criteria:

* Diagnosis:

  * For Phase 1a and Phase 1b Cohort 2, have a histologically or cytologically confirmed diagnosis of a locally advanced or metastatic solid tumor for which no standard therapy is available (per local guidance) or standard therapy has failed, or
  * For Phase 1b Cohort 1, have histologically or cytologically confirmed unresectable, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma who have not previously received systemic therapy for advanced disease
* Measurable disease: Have measurable disease on imaging based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
* Have a life expectancy of at least 3 months and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Key Exclusion Criteria:

* Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 3 weeks of the first dose of treatment
* Has persisting toxicity related to prior therapy of National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE) Grade \>1 severity
* Is expected to require any other form of systemic or localized anticancer therapy while on trial (including maintenance therapy with another agent, radiation therapy, and/or surgical resection)
* Has 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
* Has a known central nervous system metastasis(es), unless metastases are treated and stable and the individual does not require systemic corticosteroids for management of CNS symptoms at least 7 days prior to study treatment. Individuals with history of carcinomatous meningitis are excluded regardless of clinical stability.
* Has active or history of autoimmune disease that has required systemic treatment within 2 years of the start of trial treatment

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

Primary outcomes:
measure: Phase 1a Part A: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs), Graded Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0)
timeFrame: Baseline up to 28 days
Secondary outcomes:
measure: Phase 1a Part A: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: First dose date up to permanent withdrawal of GS-1423 (maximum duration: 26.3 weeks) plus 30 days
measure: Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities
timeFrame: First dose date up to permanent withdrawal of GS-1423 (maximum duration: 26.3 weeks) plus 30 days
measure: Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study
timeFrame: First dose date up to permanent withdrawal of GS-1423 (maximum duration: 26.3 weeks) plus 30 days
measure: Phase 1a Part A: Pharmacokinetic (PK) Parameter: AUCtau of GS-1423
timeFrame: Cycle 1 and Cycle 4: Day 1 (Predose, end of infusion, 2 and 6 hours post start of infusion); Days 2, 3, 5, and 8 (additionally at Day 15 in Cycle 4)
measure: Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs)
timeFrame: Baseline, during the treatment (maximum duration: 26.3 weeks), Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 4 Day 15, Cycle 6 Day 1, 30-day follow-up (30 days after discontinuation of GS-1423), post treatment follow-up (3 months)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Scottsdale Healthcare Hospitals d/b/a HonorHealth
state: Arizona
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
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: Tolcher AW, Gordon M, Mahoney KM, Seto A, Zavodovskaya M, Hsueh CH, Zhai S, Tarnowski T, Jurgensmeier JM, Stinson S, Othman AA, Chen T, Strauss J. Phase 1 first-in-human study of dalutrafusp alfa, an anti-CD73-TGF-beta-trap bifunctional antibody, in patients with advanced solid tumors. J Immunother Cancer. 2023 Feb;11(2):e005267. doi: 10.1136/jitc-2022-005267.