Clinical trial NCT04564417: First-In-Human (FIH) Study of W0180 as Single Agent and in Combination With Pembrolizumab in Adults With Locally Advanced or Metastatic Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Locally Advanced or Metastatic Solid Tumors
Keywords: advanced cancer
W0180
Lead sponsor: Pierre Fabre Medicament
Sponsor class: INDUSTRY
First posted: 2020-09-25
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Number of Participants With Dose-limiting Toxicities (DLTs) During the DLT Period
timeFrame: From Cycle 1-Day 1 up to Cycle 2-Day 1 (each cycle of 21 days)
Secondary outcomes:
measure: Escalation Part: Recommended Dose for Expansion After Administration of W0180 in Monotherapy and in Combination With Pembrolizumab
timeFrame: 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)
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
timeFrame: 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)
measure: Number of Participants With Treatment-Emergent Adverse Events by Severity
timeFrame: 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)
measure: Number of Participants With Clinically Significant Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAE)
timeFrame: 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)
measure: Number of Participants With Dose Interruptions, Dose Reductions, or Discontinuation After Administration of W0180 in Monotherapy and in Combination With Pembrolizumab
timeFrame: 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)
measure: Duration of Study Drug Exposure in Participants
timeFrame: 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)
measure: Actual and Relative Dose Intensity in Participants
timeFrame: 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)
measure: Escalation Part: Objective Response Rate (ORR/iORR)
timeFrame: Every 6 weeks for 12 months then every 8 weeks, until disease progression (Approximately 22 months)
measure: Escalation Part: Disease Control Rate (DCR) Assessed by RECIST
timeFrame: Every 6 weeks for 12 months then every 8 weeks, until disease progression (Approximately 22 months)
measure: Escalation Part: Immune Disease Control Rate (iDCR) Assessed by iRECIST
timeFrame: Every 6 weeks for 12 months then every 8 weeks, until disease progression (Approximately 22 months)
measure: Observed Maximum Plasma Concentration (Cmax)
timeFrame: From Cycle 1 Day 1 Predose to Cycle 8 Day 1: Predose (each cycle of 21 days)
measure: Experimental Half-life (T1/2)
timeFrame: From Cycle 1 Day 1 Predose to Cycle 8 Day 1: Predose (each cycle of 21 days)
measure: Area Under the Plasma Concentration-time Curve From Zero to the Last Quantifiable Point (AUC0-t)
timeFrame: From Cycle 1 Day 1 Predose to Cycle 8 Day 1: Predose (each cycle of 21 days)
measure: Total Clearance
timeFrame: From Cycle 1 Day 1 Predose to Cycle 8 Day 1: Predose (each cycle of 21 days)
measure: Number of Participants With Anti-W0180 Antibodies Post Administration of W0180 as Monotherapy and in Combination With Pembrolizumab
timeFrame: 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)
measure: Expansion Part: Objective Response Rate (ORR/iORR): Confirmed and Unconfirmed
timeFrame: Every 6 weeks for 12 months then every 8 weeks, until disease progression (Approximately 44 months)
measure: Expansion Part: Duration of response (DOR/iDOR)
timeFrame: Every 6 weeks for 12 months then every 8 weeks, until disease progression (Approximately 44 months)
measure: Expansion Part: Time to treatment response (TTR)
timeFrame: Every 6 weeks for 12 months then every 8 weeks, until disease progression (Approximately 44 months)
measure: Expansion Part: Progression Free Survival (PFS) Assessed per RECIST v1.1
timeFrame: Every 6 weeks for 12 months then every 8 weeks, until disease progression (Approximately 44 months)
measure: Expansion Part: Progression-Free Survival (iPFS) Assessed per iRECIST
timeFrame: Every 6 weeks for 12 months then every 8 weeks, until disease progression (Approximately 44 months)
measure: Expansion Part: Disease Control Rate (DCR) Assessed per RECIST v1.1
timeFrame: Every 6 weeks for 12 months then every 8 weeks, until disease progression (Approximately 44 months)
measure: Expansion Part: Disease Control Rate (iDCR) Assessed per iRECIST
timeFrame: Every 6 weeks for 12 months then every 8 weeks, until disease progression (Approximately 44 months)
measure: Expansion Part: Overall survival (OS)
timeFrame: Every 6 weeks for 12 months then every 8 weeks, until disease progression (Approximately 44 months)
Other outcomes:
Locations:
city: Lyon
country: France
facility: Centre Leon Berard, department Medical Oncology
state: Cedex
city: Toulouse
country: France
facility: IUCT, Toulouse
city: Villejuif
country: France
facility: IGR, Villejuif
city: Madrid
country: Spain
facility: CUN, Madrid
city: Pamplona
country: Spain
facility: CUN, Pamplona
Study officials:
References: