Phase I Dose Escalation Study for VIP152 in Patients With Advanced Cancer

Study Overview
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Brief Summary
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Determine the safety, tolerability, pharmacokinetics, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of VIP152 (BAY 1251152) as monotherapy or in combination in patients with solid tumors and aggressive non-hodgkin's lymphoma (NHL).

Detailed Description
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Part 2 VIP152 Monotherapy (Global). Part 3 dose escalation with VIP152 in combination with pembrolizumab (US only). Part 4 dose expansion with VIP152 in combination with pembrolizumab (US only).

Official Title
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An Open-label, Multicenter Phase I Dose Escalation Study to Characterize Safety, Tolerability, Preliminary Anti-tumor Activity, Pharmacokinetics and Maximum Tolerated Dose of VIP152 (BAY 1251152) as Monotherapy or Combination Therapy in Subjects With Advanced Cancer.

Conditions
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Neoplasms

Intervention / Treatment
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* Drug: VIP152 (BAY 1251152)
* Drug: VIP152 (BAY 1251152) 30 mg
* Drug: Keytruda
* Drug: VIP152 (BAY 1251152) 15 mg


Participation Criteria
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Eligibility Criteria
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Part 2 (Global), Part 3 (US Only), and Part 4 (US Only) Inclusion Criteria: Male or female patients aged >/=18 years Patients with a histologically or cytologically confirmed solid tumor or aggressive NHL who are refractory to or have exhausted all available therapies with MYC expression or known C-MYC amplification/alterations Adequate bone marrow, liver, and renal functions Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 In the addition to the above Part 3 (US Only) and Part 4 (US Only) Must be eligible to use pembrolizumab per USPI Exclusion Criteria: Active clinically serious infections of events > Grade 2 Subjects who have new or progressive brain or meningeal or spinal metastases. Anticancer chemotherapy or immunotherapy during the study or within 1 weeks prior to the first dose of study drug Major surgery or significant trauma within 4 weeks before the first dose of study drug Allogeneic bone marrow transplant or stem cell rescue within 4 months before first dose of study drug; patients must have completed immunosuppressive therapy before enrollment.

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: Dose escalation of VIP152 (BAY 1251152) / PART 1 (Completed)<br>Investigating VIP152 (BAY 1251152) in a dose escalation cohort in patients with solid tumors and aggressive NHL | Drug: VIP152 (BAY 1251152)<br>* The starting dose of Cohort 1 will be 5 mg IV (30 minute infusion) fixed dose once weekly (5 mg/week) for 21 day cycles.<br>|
| Experimental: Dose expansion of VIP152 (BAY 1251152) / PART 2<br>Investigating VIP152 (BAY 1251152) in a dose expansion cohort in patients with solid tumors and aggressive NHL | Drug: VIP152 (BAY 1251152) 30 mg<br>* 30 mg IV (30 minute infusion) fixed dose once weekly of a 21 day cycle.<br>|
| Experimental: Dose escalation of VIP152 (BAY 1251152) in combination with Keytruda® (pembrolizumab) / PART 3<br>Investigating combination VIP152 (BAY 1251152) and Keytruda® (pembrolizumab) in a dose escalation cohort in patients with advanced cancer. All subjects must be eligible to use pembrolizumab per USPI. | Drug: Keytruda<br>* 200 mg IV fixed dose once every 3 weeks of a 21 day cycle<br>* Other names: pembrolizumab;Drug: VIP152 (BAY 1251152) 15 mg<br>* The starting dose of Cohort 3 will be 15 mg IV (30 minute infusion) fixed dose once weekly (15 mg/week) for 21 day cycles.<br>|
| Experimental: Dose expansion of VIP152 (BAY 1251152) in combination with Keytruda® (pembrolizumab) / PART 4<br>Investigating combination VIP152 (BAY 1251152) and Keytruda® (pembrolizumab) in a dose expansion cohort in patients with advanced cancer. All subjects must be eligible to use pembrolizumab per USPI. | Drug: VIP152 (BAY 1251152) 30 mg<br>* 30 mg IV (30 minute infusion) fixed dose once weekly of a 21 day cycle.<br>Drug: Keytruda<br>* 200 mg IV fixed dose once every 3 weeks of a 21 day cycle<br>* Other names: pembrolizumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of DLT (Dose limit toxicity) of VIP152 (BAY1251152) |  | Cycle 1 Day 1 through Cycle 2 Day 1, where each cycle is up to 21 days | 
| Maximum observed drug concentration in measured matrix after single dose administration (Cmax) of VIP152 (BAY1251152) |  | Cycle 1 Day 1 through Cycle 2 Day 1, where each cycle is up to 21 days | 
| Area under the concentration versus time curve from zero to infinity after single (first) dose (AUC) of VIP152 (BAY1251152) |  | Cycle 1 Day 1 through Cycle 2 Day 1, where each cycle is up to 21 days | 
| AUC from time 0 to the last data point > Lower limit of quantitation (LLOQ) [AUC(0-tlast)] of VIP152 (BAY1251152) |  | Cycle 1 Day 1 through Cycle 2 Day 1, where each cycle is up to 21 days | 
| Maximum observed drug concentration in measured matrix after multiple dose administration during a dosage interval (Cmax,md) of VIP152 (BAY1251152) |  | Cycle 1 Day 1 through Cycle 2 Day 1, where each cycle is up to 21 days | 
| AUC from time 0 to the last data point > LLOQ after multiple dosing [AUC(0-tlast)md] of VIP152 (BAY1251152) |  | Cycle 1 Day 1 through Cycle 2 Day 1, where each cycle is up to 21 days | 
| Recommended phase 2 dose (RP2D) of VIP152 (BAY 1251152) |  | Cycle 1 Day 1 through Cycle 2 Day 1, where each cycle is up to 21 days | 
| Incidence of DLT (Dose limit toxicity) of VIP152 (BAY1251152) in combination with Keytruda® (pembrolizumab) |  | Cycle 1 Day 1 through Cycle 3 Day 1, where each cycle is up to 21 days | 
| Recommended phase 2 dose (RP2D) of VIP152 (BAY 1251152) in combination with Keytruda® (pembrolizumab) |  | Cycle 1 Day 1 through Cycle 2 Day 1, where each cycle is up to 21 days | 
| Number of participants with adverse events as a measure safety and tolarability |  | Cycle 1 Day 1 up to 30 days after the last dose, where each cycle is up to 21 days (up to approximately 36 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response evaluation based on the response criteria as applicable (RECIST v1.1 criteria for solid tumors and revised Lugano Classification for aggressive NHL) |  | Up to 3 Cycle 1 Day 1 up to 30 days after the last dose, where each cycle is up to 21 days (up to approximately 36 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid tumors, Aggressive non-hodgkin's lymphoma (NHL), Advanced Ovarian Cancer, Triple Negative Breast Cancer, DHL, Double-Hit Lymphoma, Transformed Follicular Lymphoma, Mantle Cell, Prostate Cancer, Melanoma, Non-small Cell Lung Cancer, Head and Neck Squamous Cell Cancer, Esophageal Cancer, Urothelial Carcinoma, Tumor Mutational Burden-High Cancer, Cutaneous Squamous Cell Carcinoma, Microsatellite Instability-High or Mismatch Repair Deficient Cancer, Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer, Gastric Cancer, Cervical Cancer, Hepatocellular Carcinoma, Merkel Cell Carcinoma, Renal Cell Carcinoma, Endometrial Carcinoma, MYC overexpression, MYC amplification, MYC translocation, Classic Hodgkins, Primary Mediastinal Large B Cell Lymphoma