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Study of GS-1423 in Participants With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT03954704
Recruitment Status : Terminated (The decision to discontinue the study was made based on the totality of the clinical, pharmacokinetic, and pharmacodynamic findings. No safety concerns were observed.)
First Posted : May 17, 2019
Last Update Posted : May 6, 2021
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

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 GS-1423 monotherapy in participants with advanced solid tumors.

For Phase 1a Part B, the primary objective is to assess safety and tolerability of GS-1423 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 GS-1423 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 GS-1423 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 GS-1423 monotherapy in participants with advanced solid tumors.


Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Drug: GS-1423 Drug: mFOLFOX6 Regimen Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 3, 2019
Actual Primary Completion Date : October 6, 2020
Actual Study Completion Date : April 15, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Phase 1a, Part A - Dose Escalation
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 GS-1423 of up to 45 mg/kg on Day 1 of each 2-week cycle (Q2W) until the participants meets study treatment discontinuation criteria or for up to 1 year.
Drug: GS-1423
Administered intravenously once every 2 weeks

Experimental: Phase 1a, Part B - Flat Dose Regimen
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 GS-1423 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: GS-1423
Administered intravenously

Experimental: Phase 1b, Cohort 1 (Gastric Cancer)

Safety run-in: A standard 3+3 dose escalation design will be used to determine the DLT and MTD or RP2D of GS-1423 in combination with mFOLFOX6. The planned starting dose of GS-1423 will be targeted to achieve the exposure at -1 dose of RP2D monotherapy (Q2W) determined from Phase 1a. GS-1423 will be administered in combination with mFOLFOX6.

Post safety run-in: Approximately 70 participants will be enrolled to receive GS-1423 at the dose level determined from the safety run-in period, in combination with mFOLFOX6 regimen.

Participants will receive GS-1423 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: GS-1423
Administered intravenously once every 2 weeks

Drug: mFOLFOX6 Regimen
Chemotherapy regimen of oxaliplatin, 5-fluorouracil [5-FU], and leucovorin

Experimental: Phase 1b, Cohort 2 (Paired Biopsy)
Participants will receive GS-1423 at the dose level determined from Phase 1a Q2W until the participants meets study treatment discontinuation criteria or for up to 1 year.
Drug: GS-1423
Administered intravenously once every 2 weeks




Primary Outcome Measures :
  1. For Phase 1a Part A, Phase 1b Cohort 1 Safety Run-in, Percentage of Participants who had Dose Limiting Toxicities (DLTs) in Dose Escalation During the First 28 Days of Treatment [ Time Frame: Up to 28 days ]
    DLTs refer to toxicities experienced during the first 28 days of study treatment that have been judged to be clinically significant and related to study treatment.

  2. For Phase 1b Cohort 1 Post Safety Run-in, Confirmed Objective Response Rate per RECIST 1.1, as Determined by Investigator [ Time Frame: Up to 3 years ]
    The objective response rate (ORR) is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.

  3. For Phase 1a Part B, Percentage of Participants Experiencing Treatment-Emergent Adverse Events [ Time Frame: First dose date up to 1 year plus 30 days ]
  4. For Phase 1b Cohort 2, Percentage of Participants Experiencing Treatment-Emergent Adverse Events [ Time Frame: First dose date up to 1 year plus 30 days ]
  5. For Phase 1a Part B, Percentage of Participants Experiencing Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities [ Time Frame: First dose date up to 1 year plus 30 days ]
  6. For Phase 1b Cohort 2, Percentage of Participants Experiencing Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities [ Time Frame: First dose date up to 1 year plus 30 days ]
  7. For Phase 1a Part B, Percentage of Participants with Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) [ Time Frame: First dose date up to 1 year plus 30 days ]
  8. For Phase 1b Cohort 2, Percentage of Participants with Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) [ Time Frame: First dose date up to 1 year plus 30 days ]

Secondary Outcome Measures :
  1. For Phase 1a Part A and Phase 1a Part B, Pharmacokinetic (PK) Parameter: AUCtau of GS-1423 [ Time Frame: Predose and 2, 6, 24, 48, 96, 168 hours postdose ]
    AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

  2. For Phase 1a Part A and Phase 1a Part B, Percentage of Participants Experiencing Anti-Drug Antibody (ADA) Formation [ Time Frame: Up to Posttreatment Month 3 ]
  3. For Phase 1a Part A, Percentage of Participants Experiencing Treatment-Emergent Adverse Events [ Time Frame: First dose date up to 1 year plus 30 days ]
  4. For Phase 1b Cohort 1, Percentage of Participants Experiencing Treatment-Emergent Adverse Events [ Time Frame: First dose date up to 2 years plus 30 days ]
  5. For Phase 1a Part A, Percentage of Participants Experiencing Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities [ Time Frame: First dose date up to 1 year plus 30 days ]
  6. For Phase 1b Cohort 1, Percentage of Participants Experiencing Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities [ Time Frame: First dose date up to 2 years plus 30 days ]
  7. For Phase 1a Part A, Percentage of Participants with Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) [ Time Frame: First dose date up to 1 year plus 30 days ]
  8. For Phase 1b Cohort 1, Percentage of Participants with Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) [ Time Frame: First dose date up to 2 years plus 30 days ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03954704


Locations
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United States, Arizona
Scottsdale Healthcare Hospitals d/b/a HonorHealth
Scottsdale, Arizona, United States, 85258
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Texas
Mary Crowley Cancer Research
Dallas, Texas, United States, 75230
NEXT Oncology
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences
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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT03954704    
Other Study ID Numbers: GS-US-505-5452
2019-004938-41 ( EudraCT Number )
First Posted: May 17, 2019    Key Record Dates
Last Update Posted: May 6, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms