Clinical Trials/NCT04564417

NCT04564417

Terminated

Phase 1

Phase I Dose Escalation and Dose Expansion, International, Multicenter Study of W0180 as Single Agent and in Combination With Pembrolizumab (Anti-PD-1) in Adult Participants With Locally Advanced or Metastatic Solid Tumors

Pierre Fabre Medicament5 sites in 2 countries33 target enrollmentSeptember 8, 2020

ConditionsLocally Advanced or Metastatic Solid Tumors

InterventionsW0180 Pembrolizumab

DrugsPembrolizumab

Overview

Phase: Phase 1
Intervention: W0180
Conditions: Locally Advanced or Metastatic Solid Tumors
Sponsor: Pierre Fabre Medicament
Enrollment: 33
Locations: 5
Primary Endpoint: Number of Participants With Dose-limiting Toxicities (DLTs) During the DLT Period
Status: Terminated
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study will be to determine the Maximum Tolerated Dose (MTD) and describe dose-limiting toxicities (DLTs) of W0180 given as monotherapy and in combination with pembrolizumab (anti-PD-1).

Registry

clinicaltrials.gov

Start Date

September 8, 2020

End Date

December 19, 2023

Last Updated

2 years ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Pierre Fabre Medicament

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Histologically or cytologically confirmed diagnosis of locally advanced or metastatic solid tumors, whose disease has progressed or for whom no further standard therapy is available or appropriate
•Evidence of measurable disease as determined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (or modified RECIST 1.1 for mesothelioma)
•Adequate blood counts at baseline
•Adequate liver function at screening and baseline
•Sexually active participants must use medically acceptable methods of contraception during the course of this study

Exclusion Criteria

•Participants previously treated with an anti-V-domain Ig suppressor of T cell activation (VISTA) (small molecule or antibody) agent
•Participants with known central nervous system (CNS) metastases and/or carcinomatous meningitis
•History of severe hypersensitivity reactions to other monoclonal antibodies
•Positive for hepatitis B virus(HBV), hepatitis C virus (HCV) or HIV infection
•History of anti-cancer therapies within the last 4 weeks (or \<=5 half-lives for targeted agents) prior to initiating study treatment.

Arms & Interventions

Monotherapy dose escalation: W0180

Participants will receive W0180 in a 21-day cycle until the maximum tolerated dose (MTD)/ recommended dose for expansion (RDE) for the single-agent identified.

Intervention: W0180

Combination dose escalation: W0180+Pembrolizumab

Participants will receive Pembrolizumab 200 mg flat dose as IV infusion every three weeks (Q3W) followed by W0180 in a 21-day Cycle until the MTD in combination is identified or an RDE in combination is established.

Intervention: W0180

Combination dose escalation: W0180+Pembrolizumab

Intervention: Pembrolizumab

Dose expansion

Participants will receive Pembrolizumab 200 mg flat dose as IV infusion Q3W followed by an RDE dose of W0180 in a 21-day cycle.

Intervention: W0180

Dose expansion

Participants will receive Pembrolizumab 200 mg flat dose as IV infusion Q3W followed by an RDE dose of W0180 in a 21-day cycle.

Intervention: Pembrolizumab

Outcomes

Primary Outcomes

Number of Participants With Dose-limiting Toxicities (DLTs) During the DLT Period

Time Frame: From Cycle 1-Day 1 up to Cycle 2-Day 1 (each cycle of 21 days)

The DLTs will be classified according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.

Secondary Outcomes

Expansion Part: Disease Control Rate (DCR) Assessed per RECIST v1.1(Every 6 weeks for 12 months then every 8 weeks, until disease progression (Approximately 44 months))
Number of Participants With Clinically Significant Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAE)(From the first study treatment infusion in Cycle 1 (each cycle of 21 days) until the safety follow-up in expansion part (approximately 44 months))
Number of Participants With Dose Interruptions, Dose Reductions, or Discontinuation After Administration of W0180 in Monotherapy and in Combination With Pembrolizumab(From the first study treatment infusion in Cycle 1 (each cycle of 21 days) until the safety follow-up in expansion part (approximately 44 months))
Escalation Part: Immune Disease Control Rate (iDCR) Assessed by iRECIST(Every 6 weeks for 12 months then every 8 weeks, until disease progression (Approximately 22 months))
Experimental Half-life (T1/2)(From Cycle 1 Day 1 Predose to Cycle 8 Day 1: Predose (each cycle of 21 days))
Expansion Part: Time to treatment response (TTR)(Every 6 weeks for 12 months then every 8 weeks, until disease progression (Approximately 44 months))
Escalation Part: Disease Control Rate (DCR) Assessed by RECIST(Every 6 weeks for 12 months then every 8 weeks, until disease progression (Approximately 22 months))
Observed Maximum Plasma Concentration (Cmax)(From Cycle 1 Day 1 Predose to Cycle 8 Day 1: Predose (each cycle of 21 days))
Area Under the Plasma Concentration-time Curve From Zero to the Last Quantifiable Point (AUC0-t)(From Cycle 1 Day 1 Predose to Cycle 8 Day 1: Predose (each cycle of 21 days))
Number of Participants With Anti-W0180 Antibodies Post Administration of W0180 as Monotherapy and in Combination With Pembrolizumab(From the first study treatment infusion in Cycle 1 (each cycle of 21 days) until the safety follow-up in expansion part (approximately 44 months))
Number of Participants With Treatment-Emergent Adverse Events by Severity(From the first study treatment infusion in Cycle 1 (each cycle of 21 days) until the safety follow-up in expansion part (approximately 44 months))
Duration of Study Drug Exposure in Participants(From the first study treatment infusion in Cycle 1 (each cycle of 21 days) until the safety follow-up in expansion part (approximately 44 months))
Actual and Relative Dose Intensity in Participants(From the first study treatment infusion in Cycle 1 (each cycle of 21 days) until the safety follow-up in expansion part (approximately 44 months))
Expansion Part: Overall survival (OS)(Every 6 weeks for 12 months then every 8 weeks, until disease progression (Approximately 44 months))
Escalation Part: Recommended Dose for Expansion After Administration of W0180 in Monotherapy and in Combination With Pembrolizumab(From the first study treatment infusion in Cycle 1 (each cycle of 21 days) until the safety follow-up in Combination dose escalation cohort (30 days after last study infusion administration) (approximately 22 months))
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)(From the first study treatment infusion in Cycle 1 (each cycle of 21 days) until the safety follow-up in expansion part (approximately 44 months))
Escalation Part: Objective Response Rate (ORR/iORR)(Every 6 weeks for 12 months then every 8 weeks, until disease progression (Approximately 22 months))
Total Clearance(From Cycle 1 Day 1 Predose to Cycle 8 Day 1: Predose (each cycle of 21 days))
Expansion Part: Objective Response Rate (ORR/iORR): Confirmed and Unconfirmed(Every 6 weeks for 12 months then every 8 weeks, until disease progression (Approximately 44 months))
Expansion Part: Progression Free Survival (PFS) Assessed per RECIST v1.1(Every 6 weeks for 12 months then every 8 weeks, until disease progression (Approximately 44 months))
Expansion Part: Progression-Free Survival (iPFS) Assessed per iRECIST(Every 6 weeks for 12 months then every 8 weeks, until disease progression (Approximately 44 months))
Expansion Part: Duration of response (DOR/iDOR)(Every 6 weeks for 12 months then every 8 weeks, until disease progression (Approximately 44 months))
Expansion Part: Disease Control Rate (iDCR) Assessed per iRECIST(Every 6 weeks for 12 months then every 8 weeks, until disease progression (Approximately 44 months))