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

Gilead Sciences

Status and phase: Terminated; Phase 1

Conditions: Advanced Solid Tumors

Treatments: Drug: Dalutrafusp alfa; Drug: mFOLFOX6 Regimen

Study type: Interventional

Funder types: Industry

Identifiers

NCT03954704

2019-004938-41 (EudraCT Number)

GS-US-505-5452

Details and patient eligibility

About

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.

Enrollment: 22 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

22 participants in 4 patient groups

Phase 1a, Part A - Dose Escalation

Experimental group

Description:

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.

Treatment:

Drug: Dalutrafusp alfa

Drug: Dalutrafusp alfa

Phase 1a, Part B - Flat Dose Regimen

Experimental group

Description:

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.

Treatment:

Drug: Dalutrafusp alfa

Drug: Dalutrafusp alfa

Phase 1b, Cohort 1 (Gastric Cancer)

Experimental group

Description:

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.

Treatment:

Drug: Dalutrafusp alfa

Drug: Dalutrafusp alfa

Drug: mFOLFOX6 Regimen

Phase 1b, Cohort 2 (Paired Biopsy)

Experimental group

Description:

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.

Treatment:

Drug: Dalutrafusp alfa

Drug: Dalutrafusp alfa