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

Advanced Solid Tumors Clinical Trial

Official title:

A Phase 1b/2 Dose Escalation/Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of GS-4224 in Subjects With Advanced Solid Tumors

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04049617
• Other study ID #: GS-US-494-5484
• Secondary ID: 2019-004605-27
• Status: Terminated
• Phase: Phase 1
• Start date: August 26, 2019
• Est. completion date: March 30, 2021

Study information

• Verified date: September 2022
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This was a planned Phase 1/2 study. However, Phase 2 was not conducted because the study was closed due to sponsor decision prior to opening the dose expansion cohort and hence, RP2D analysis was not performed.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 18
• Est. completion date: March 30, 2021
• Est. primary completion date: March 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• 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.

Key Exclusion Criteria:

• 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).

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

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Drug:
• Evixapodlin
Tablets administered orally.

Locations

Country	Name	City	State
New Zealand	Auckland City Hospital	Auckland
New Zealand	Christchurch Clinical Studies Trust, LLC	Christchurch
New Zealand	Auckland Clinical Studies Ltd	Grafton, Auckland
United States	California Care Associates for Research and Excellence Inc	Encinitas	California
United States	NEXT Oncology	San Antonio	Texas
United States	Northwest Medical Specialties, PLLC	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Pharmacokinetic (PK) Parameter: AUCtau of Evixapodlin During the Dose Escalation Phase	AUCtau was defined as area under the concentration-time curve from time zero to the end of the dosing interval.	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
Secondary	PK Parameter: Cmax of Evixapodlin During the Dose Escalation Phase	Cmax was defined as the maximum observed drug concentration.	Intensive PK: Predose, 0.5, 1, 1.5, 2.5, 4, 6, 24 h postdose (400-1500 QD mg cohorts) on C1D1 & D15
Secondary	PK Parameter: Ctrough of Evixapodlin During the Dose Escalation Phase	Ctrough is defined as the observed concentration at the end of the dosing interval.	Intensive PK: Predose, 0.5, 1, 1.5, 2.5, 4, 6, 24 h postdose (400-1500 QD mg cohorts) on C1D1 & D15
Secondary	PK Parameter: Tmax of Evixapodlin During the Dose Escalation Phase	Tmax is defined as the time to maximum observed concentration.	Intensive PK: Predose, 0.5, 1, 1.5, 2.5, 4, 6, 24 h postdose (400-1500 QD mg cohorts) on C1D1 & D15
Secondary	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
Secondary	Percentage of Participants Experiencing = Grade 3 Treatment-Emergent Laboratory Abnormalities During the Dose Expansion Phase		First dose date through end of treatment plus 30 days, approximately 5 years