Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of Evixapodlin (Formerly GS-4224) in Participants With Advanced Solid Tumors

NCT04049617 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: GS-US-494-54842019-004605-27
• Study Type: interventional
• Target: 18
• Locations: 2 countries
• Sites: 6

Brief Summary

The primary objectives of this study are to characterize the safety and tolerability of evixapodlin (formerly GS-4224) and to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of evixapodlin in participants with advanced solid tumors.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (1)

• Number of Participants Experiencing Dose Limiting Toxicities (DLTs) During the Dose Escalation Phase

  A DLT was any toxicity defined as follows excluding toxicities clearly related to disease progression or disease-related processes occurring during the DLT assessment window (Day 1 through Day 21): * Grade ≥ 4 neutropenia * Grade ≥ 3 neutropenia with fever * Grade ≥ 3 thrombocytopenia * Grade ≥ 2 bleeding * Grade ≥ 3 anemia * Grade ≥ 3 or higher non-hematologic toxicity (excluding Grade 3 nausea or emesis or Grade 3 diarrhea) * Grade ≥ 2 non-hematologic treatment-emergent adverse event that in the opinion of the investigator is of potential clinical significance * Treatment interruption of ≥ 7 days due to unresolved toxicity * Any toxicity event that precludes further administration of evixapodlin * Any Grade 3 or Grade 4 elevation in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) associated with a Grade 2 elevation in bilirubin lasting ≥ 7 days * An immune-related adverse event (irAE) for which immunotherapy should be permanently discontinued

  Day 1 through Day 21

Secondary Outcomes (6)

• Pharmacokinetic (PK) Parameter: AUCtau of Evixapodlin During the Dose Escalation Phase

  Intensive PK: Predose, 0.5, 1, 1.5, 2.5, 4, 6, 24 hours (h) postdose (400-1500 once daily [QD] mg cohorts) on Cycle (C) 1 Day (D) 1 & D15

• PK Parameter: Cmax of Evixapodlin During the Dose Escalation Phase

  Intensive PK: Predose, 0.5, 1, 1.5, 2.5, 4, 6, 24 h postdose (400-1500 QD mg cohorts) on C1D1 & D15

• PK Parameter: Ctrough of Evixapodlin During the Dose Escalation Phase

  Intensive PK: Predose, 0.5, 1, 1.5, 2.5, 4, 6, 24 h postdose (400-1500 QD mg cohorts) on C1D1 & D15

• PK Parameter: Tmax of Evixapodlin During the Dose Escalation Phase

  Intensive PK: Predose, 0.5, 1, 1.5, 2.5, 4, 6, 24 h postdose (400-1500 QD mg cohorts) on C1D1 & D15

• Percentage of Participants Experiencing ≥ Grade 3 Treatment-Emergent Adverse Events During the Dose Expansion Phase

  First dose date through end of treatment plus 30 days, approximately 5 years

Study Arms (9)

Cohort 1: Evixapodlin 400 mg (Phase 1)

EXPERIMENTAL

Participants will receive Evixapodlin 400 mg once daily for 21 days of each cycle.

Drug: Evixapodlin

Cohort 2: Evixapodlin 700 mg (Phase 1)

EXPERIMENTAL

Participants will receive Evixapodlin 700 mg once daily for 21 days of each cycle.

Drug: Evixapodlin

Cohort 3: Evixapodlin 1000 mg (Phase 1)

EXPERIMENTAL

Participants will receive Evixapodlin 1000 mg once daily for 21 days of each cycle.

Drug: Evixapodlin

Cohort 4: Evixapodlin 1500 mg (Phase 1)

EXPERIMENTAL

Participants will receive Evixapodlin 1500 mg once daily for 21 days of each cycle.

Drug: Evixapodlin

Cohort 5: Evixapodlin 1000 mg (Phase 1)

EXPERIMENTAL

Participants are planned to receive Evixapodlin 1000 mg twice daily (BID) for 21 days of each cycle.

Drug: Evixapodlin

Cohort 1 Substudy: Evixapodlin 400 mg (Phase 1)

EXPERIMENTAL

Participants will receive Evixapodlin 400 mg once daily for 21 days of each cycle.

Drug: Evixapodlin

Cohort 2 Substudy: Evixapodlin 700 mg (Phase 1)

EXPERIMENTAL

Participants are planned to receive Evixapodlin 700 mg once daily for 21 days of each cycle.

Drug: Evixapodlin

Cohort 3 Substudy: Evixapodlin 1000 mg (Phase 1)

EXPERIMENTAL

Participants will receive Evixapodlin 1000 mg once daily for 21 days of each cycle.

Drug: Evixapodlin

Dose Expansion (Phase 2)

EXPERIMENTAL

Dose expansion is planned to begin when the recommended Phase 2 dose (RP2D) will be determined.

Drug: Evixapodlin

Interventions

Evixapodlin DRUG

Tablets administered orally.

Also known as: GS-4224

Cohort 1 Substudy: Evixapodlin 400 mg (Phase 1); Cohort 1: Evixapodlin 400 mg (Phase 1); Cohort 2 Substudy: Evixapodlin 700 mg (Phase 1); Cohort 2: Evixapodlin 700 mg (Phase 1); Cohort 3 Substudy: Evixapodlin 1000 mg (Phase 1); Cohort 3: Evixapodlin 1000 mg (Phase 1); Cohort 4: Evixapodlin 1500 mg (Phase 1); Cohort 5: Evixapodlin 1000 mg (Phase 1); Dose Expansion (Phase 2)

Eligibility Criteria

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

You may qualify if:

• Dose Escalation Cohorts: Histologically or cytologically confirmed advanced malignant solid tumor that is refractory to or intolerant of all standard therapy or for which no standard therapy is available.
• Dose Expansion and 1000 mg twice a day (BID) Dose Escalation Cohorts: Individuals must have available sufficient and adequate formalin fixed tumor sample preferably from a biopsy of a tumor lesion obtained either at the time of or after the diagnosis of advanced disease has been made and from a site not previously irradiated. Alternatively, individuals must agree to have a biopsy taken prior to entering the study to provide adequate tissue. For the 1000 mg BID dose escalation cohort, individuals with melanoma, Merkel cell, microsatellite instability-high (MSI-H) cancers, and classical Hodgkin lymphoma (cHL) are not required to have archival or fresh biopsy tissue.
• Dose Escalation Biopsy Substudy and 1000 mg BID Dose Escalation Cohorts: Documented ligand 1 of programmed cell death protein 1 (PD-L1) expression in the tumor (tumor proportion score (TPS) ≥ 10% or combined positive score (CPS) ≥ 10). In the 1000 mg BID Cohort, PD-L1 expression will not be required for Merkel cell, melanoma, MSI-H cancers, and cHL.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
• Adequate organ function.

You may not qualify if:

• History or evidence of clinically significant disorder, condition, or disease that, in the opinion of the Investigator or Medical Monitor would pose a risk to individual safety or interfere with the study evaluations, procedures, or completion.
• Dose Escalation Cohorts: History of ≥ Grade 3 Adverse Events (AEs) during prior treatment with an immune checkpoint inhibitor, or history of discontinuation of treatment with an immune checkpoint inhibitor due to AEs.
• Dose Escalation 1000 mg BID and Dose Expansion Cohort: Prior treatment with an immune checkpoint inhibitor (anti-PD-1, anti-PD-L1, or anti- ligand 2 of programmed cell death protein 1 (PD-L2) antibodies).
• History of autoimmune disease (for example, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis).

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (6)

California Care Associates for Research and Excellence Inc

Encinitas, California, 92024, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

Northwest Medical Specialties, PLLC

Tacoma, Washington, 98405, United States

Location

Auckland City Hospital

Auckland, 1023, New Zealand

Location

Christchurch Clinical Studies Trust, LLC

Christchurch, 8011, New Zealand

Location

Auckland Clinical Studies Ltd

Grafton, Auckland, 1010, New Zealand

Location

Related Publications (1)

• Odegard JM, Othman AA, Lin KW, Wang AY, Nazareno J, Yoon OK, Ling J, Lad L, Dunbar PR, Thai D, Ang E, Waldron N, Deva S. Oral PD-L1 inhibitor GS-4224 selectively engages PD-L1 high cells and elicits pharmacodynamic responses in patients with advanced solid tumors. J Immunother Cancer. 2024 Apr 11;12(4):e008547. doi: 10.1136/jitc-2023-008547.

  PMID: 38604815 DERIVED

Limitations and Caveats

Due to early termination, the study did not proceed to dose expansion phase.

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: July 31, 2019
• First Posted: August 8, 2019
• Study Start: August 26, 2019
• Primary Completion: March 30, 2021
• Study Completion: March 30, 2021
• Last Updated: October 6, 2022
• Results First Posted: August 10, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); NZ (3)