First-In-Human (FIH) Study of W0180 as Single Agent and in Combination With Pembrolizumab in Adults With Locally Advanced or Metastatic Solid Tumors

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Locally Advanced or Metastatic Solid Tumors

Intervention / Treatment
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* Biological: W0180
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Monotherapy dose escalation: W0180<br>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. | Biological: W0180<br>* Participants will receive W0180 in a 21-day cycle.<br>|
| Experimental: Combination dose escalation: W0180+Pembrolizumab<br>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. | Biological: W0180<br>* Participants will receive W0180 in a 21-day cycle.<br>Drug: Pembrolizumab<br>* Participants will receive Pembrolizumab 200 mg flat dose as IV infusion every three weeks (Q3W) in a 21-day cycle.<br>|
| Experimental: Dose expansion<br>Participants will receive Pembrolizumab 200 mg flat dose as IV infusion Q3W followed by an RDE dose of W0180 in a 21-day cycle. | Biological: W0180<br>* Participants will receive W0180 in a 21-day cycle.<br>Drug: Pembrolizumab<br>* Participants will receive Pembrolizumab 200 mg flat dose as IV infusion every three weeks (Q3W) in a 21-day cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Dose-limiting Toxicities (DLTs) During the DLT Period | The DLTs will be classified according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. | From Cycle 1-Day 1 up to Cycle 2-Day 1 (each cycle of 21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Escalation Part: Recommended Dose for Expansion After Administration of W0180 in Monotherapy and in Combination With Pembrolizumab | The RDE will be the dose of W0180 chosen for the dose-expansion part. | 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) | Treatment-Emergent Adverse Events (TEAEs)/Treatment-Emergent Serious Adverse Events (TESAEs) are any new event that starts after the first administration of study treatment and less than or equal to (<=) 30 days after treatment discontinuation or that worsened during that study period. | 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 | The severity of the AEs are categorized into Grades 1 to 5: Grade 1: Mild- asymptomatic or mild symptoms, Grade 2: Moderate- minimal; local or noninvasive intervention indicated, Grade 3: Severe or medically significant but not immediately life-threatening, Grade 4: Life-threatening consequences, and Grade 5: Death related to AE. An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAE is any new event that starts after the first administration of study treatment and <=30 days after treatment discontinuation or that worsened during that study period. | 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 Clinically Significant Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAE) | Number of participants with clinically significant abnormalities in laboratory parameters (hematology, blood chemistry, coagulation parameters, thyroid function, urinalysis, cytokines and tryptase) will be assessed after administration of W0180 in monotherapy and in combination with pembrolizumab for both escalation and expansion part of study. | 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 | The number of participants reporting dose interruptions, dose reductions, and temporary or definitive discontinuation after administration of W0180 in monotherapy and in combination with pembrolizumab for both escalation and expansion part of study will be assessed. | 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 | The duration of study treatment exposure will be summarized after the administration of W0180 in monotherapy and in combination with pembrolizumab for both escalation and expansion part of the study. | 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 | Participants with actual and relative dose intensity will be summarized and assessed 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: Objective Response Rate (ORR/iORR) | The ORR/iORR will be assessed and reported per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and per immune Response Evaluation Criteria in Solid Tumors (iRECIST). | Every 6 weeks for 12 months then every 8 weeks, until disease progression (Approximately 22 months) | 
| Escalation Part: Disease Control Rate (DCR) Assessed by RECIST | The DCR will be assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. | Every 6 weeks for 12 months then every 8 weeks, until disease progression (Approximately 22 months) | 
| Escalation Part: Immune Disease Control Rate (iDCR) Assessed by iRECIST | The iDCR will be assessed and reported per immune Response Evaluation Criteria in Solid Tumors (iRECIST). | Every 6 weeks for 12 months then every 8 weeks, until disease progression (Approximately 22 months) | 
| Observed Maximum Plasma Concentration (Cmax) | Cmax will be assessed after administration of W0180 in monotherapy and in combination with pembrolizumab. | From Cycle 1 Day 1 Predose to Cycle 8 Day 1: Predose (each cycle of 21 days) | 
| Experimental Half-life (T1/2) | T1/2 will be assessed after administration of W0180 in monotherapy and in combination with pembrolizumab. | 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) | AUC0-t will be assessed after administration of W0180 in monotherapy and in combination with pembrolizumab. | From Cycle 1 Day 1 Predose to Cycle 8 Day 1: Predose (each cycle of 21 days) | 
| Total Clearance | Total Clearance will be Calculated as the Ratio of the Dose and the total area under the plasma concentration-time curve (AUCinf). CLtot will be assessed after administration of W0180 in monotherapy and in combination with pembrolizumab. | 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) | 
| Expansion Part: Objective Response Rate (ORR/iORR): Confirmed and Unconfirmed | ORR/iORR will be assessed and reported per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and per immune Response Evaluation Criteria in Solid Tumors (iRECIST). | Every 6 weeks for 12 months then every 8 weeks, until disease progression (Approximately 44 months) | 
| Expansion Part: Duration of response (DOR/iDOR) | The DOR/iDOR will be assessed and reported per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and per immune Response Evaluation Criteria in Solid Tumors (iRECIST). | Every 6 weeks for 12 months then every 8 weeks, until disease progression (Approximately 44 months) | 
| Expansion Part: Time to treatment response (TTR) | The TTR will be assessed and reported per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and per immune Response Evaluation Criteria in Solid Tumors (iRECIST). | 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 | The progression free survival will be assessed and reported per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. | 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 | The iPFS will be assessed and reported per immune Response Evaluation Criteria in Solid Tumors (iRECIST). | Every 6 weeks for 12 months then every 8 weeks, until disease progression (Approximately 44 months) | 
| Expansion Part: Disease Control Rate (DCR) Assessed per RECIST v1.1 | The DCR will be assessed and reported per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. | 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 | The iDCR will be assessed and reported per immune Response Evaluation Criteria in Solid Tumors (iRECIST). | Every 6 weeks for 12 months then every 8 weeks, until disease progression (Approximately 44 months) | 
| Expansion Part: Overall survival (OS) | OS is defined as time duration which was measured from the date of first dose to the date of death due to any cause. | Every 6 weeks for 12 months then every 8 weeks, until disease progression (Approximately 44 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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advanced cancer, W0180