Study of Dalutrafusp Alfa (Formerly GS-1423) in Participants With Advanced Solid Tumors

NCT03954704 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: GS-US-505-54522019-004938-41
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 4

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.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (1)

• 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)

  DLT was defined as: Grade 3 thrombocytopenia with bleeding; Grade ≥ 3 febrile neutropenia; any Grade 4 hematologic laboratory abnormalities/adverse events (AEs) (except Grade 4 lymphopenia and anaemia, Grade 4 neutropenia lasting ≤ 7 days with no fever); Grade 4 non-hematologic AEs; any ≥Grade 2 uveitis, blurred vision, eye pain, and/or reduction of visual acuity that did not respond to topical therapy and did not improve to Grade 1 severity within 2 weeks of topical therapy initiation or required systemic treatment; Grade 3 non-hematologic AEs; any other non-immune-related Grade 3 AE (except any Grade 3 endocrinopathy; Grade 3 AE of tumor flare; transient \[≤ 3 days\] Grade 3 fatigue, local reactions, headache, nausea, emesis, or diarrhea and/or resolved to Grade ≤ 1; transient Grade 3 flu-like symptoms or fever); inability to receive first 2 doses of GS-1423 or \> 2-week delay in starting next cycle of therapy due to a treatment-related toxicity; Grade 5 event (death).

  Baseline up to 28 days

Secondary Outcomes (5)

• Phase 1a Part A: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)

  First dose date up to permanent withdrawal of GS-1423 (maximum duration: 26.3 weeks) plus 30 days

• Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities

  First dose date up to permanent withdrawal of GS-1423 (maximum duration: 26.3 weeks) plus 30 days

• Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study

  First dose date up to permanent withdrawal of GS-1423 (maximum duration: 26.3 weeks) plus 30 days

• Phase 1a Part A: Pharmacokinetic (PK) Parameter: AUCtau of GS-1423

  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)

• Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs)

  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)

Study Arms (4)

Phase 1a, Part A - Dose Escalation

EXPERIMENTAL

Part A will consist of dose escalation by an accelerated dosing design and a 3+3 dose escalation scheme. Participants will receive escalating dose levels dalutrafusp alfa of up to 45 mg/kg on Day 1 of each 2-week cycle (Q2W) until the participant meets study treatment discontinuation criteria or for up to 1 year.

Drug: Dalutrafusp alfa

Phase 1a, Part B - Flat Dose Regimen

EXPERIMENTAL

Part B will consist of 3 adaptive cohorts. Based on PK, pharmacodynamics, and safety results from the Part A study, participants will be administered a flat dose of dalutrafusp alfa on Day 1 of each cycle QW, Q2W and/or every 3 weeks (Q3W) until the participant meets study treatment discontinuation criteria or for up to 1 year.

Drug: Dalutrafusp alfa

Phase 1b, Cohort 1 (Gastric Cancer)

EXPERIMENTAL

Safety run-in: A standard 3+3 dose escalation design will be used to determine the DLT and MTD or RP2D of dalutrafusp alfa in combination with mFOLFOX6. The planned starting dose of dalutrafusp alfa will be targeted to achieve the exposure at -1 dose of RP2D monotherapy (Q2W) determined from Phase 1a. Dalutrafusp alfa will be administered in combination with mFOLFOX6. Post safety run-in: Approximately 70 participants will be enrolled to receive dalutrafusp alfa at the dose level determined from the safety run-in period, in combination with mFOLFOX6 regimen. Participants will receive dalutrafusp alfa on Day 1 of each 14-day cycle up to 2 years until PD, or unacceptable toxicity, substantial noncompliance with study procedures or study drug, study discontinuation or withdrawal from study. Participants will also receive mFOLFOX6 regimen Q2W for up to 12 cycles.

Drug: Dalutrafusp alfa; Drug: mFOLFOX6 Regimen

Phase 1b, Cohort 2 (Paired Biopsy)

EXPERIMENTAL

Participants will receive dalutrafusp alfa at the dose level determined from Phase 1a Q2W until the participants meets study treatment discontinuation criteria or for up to 1 year.

Drug: Dalutrafusp alfa

Interventions

Dalutrafusp alfa DRUG

Administered intravenously

Also known as: GS-1423

Phase 1a, Part A - Dose Escalation; Phase 1b, Cohort 1 (Gastric Cancer); Phase 1b, Cohort 2 (Paired Biopsy)

mFOLFOX6 Regimen DRUG

Chemotherapy regimen of oxaliplatin, 5-fluorouracil \[5-FU\], and leucovorin

Phase 1b, Cohort 1 (Gastric Cancer)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (4)

Scottsdale Healthcare Hospitals d/b/a HonorHealth

Scottsdale, Arizona, 85258, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Mary Crowley Cancer Research

Dallas, Texas, 75230, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

• 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.

  PMID: 36746510 BACKGROUND

Related Links

• Gilead Clinical Trials Website

Limitations and Caveats

Because the study was terminated after enrolling only 22 participants in the dose-escalation stage (Phase 1a Part A), planned analysis was not conducted for Phase 1a Part B, and Phase 1b.

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2019
• First Posted: May 17, 2019
• Study Start: June 3, 2019
• Primary Completion: October 27, 2020
• Study Completion: April 15, 2021
• Last Updated: November 21, 2023
• Results First Posted: November 21, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)