Clinical trial NCT02635672: Phase I Dose Escalation Study for VIP152 in Patients With Advanced Cancer
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Keywords: 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
Lead sponsor: Vincerx Pharma, Inc.
Sponsor class: INDUSTRY
First posted: 2015-12-21
Enrollment: 110
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: 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: 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of DLT (Dose limit toxicity) of VIP152 (BAY1251152)
timeFrame: Cycle 1 Day 1 through Cycle 2 Day 1, where each cycle is up to 21 days
measure: Maximum observed drug concentration in measured matrix after single dose administration (Cmax) of VIP152 (BAY1251152)
timeFrame: Cycle 1 Day 1 through Cycle 2 Day 1, where each cycle is up to 21 days
measure: Area under the concentration versus time curve from zero to infinity after single (first) dose (AUC) of VIP152 (BAY1251152)
timeFrame: Cycle 1 Day 1 through Cycle 2 Day 1, where each cycle is up to 21 days
measure: AUC from time 0 to the last data point > Lower limit of quantitation (LLOQ) [AUC(0-tlast)] of VIP152 (BAY1251152)
timeFrame: Cycle 1 Day 1 through Cycle 2 Day 1, where each cycle is up to 21 days
measure: Maximum observed drug concentration in measured matrix after multiple dose administration during a dosage interval (Cmax,md) of VIP152 (BAY1251152)
timeFrame: Cycle 1 Day 1 through Cycle 2 Day 1, where each cycle is up to 21 days
measure: AUC from time 0 to the last data point > LLOQ after multiple dosing [AUC(0-tlast)md] of VIP152 (BAY1251152)
timeFrame: Cycle 1 Day 1 through Cycle 2 Day 1, where each cycle is up to 21 days
measure: Recommended phase 2 dose (RP2D) of VIP152 (BAY 1251152)
timeFrame: Cycle 1 Day 1 through Cycle 2 Day 1, where each cycle is up to 21 days
measure: Incidence of DLT (Dose limit toxicity) of VIP152 (BAY1251152) in combination with Keytruda® (pembrolizumab)
timeFrame: Cycle 1 Day 1 through Cycle 3 Day 1, where each cycle is up to 21 days
measure: Recommended phase 2 dose (RP2D) of VIP152 (BAY 1251152) in combination with Keytruda® (pembrolizumab)
timeFrame: Cycle 1 Day 1 through Cycle 2 Day 1, where each cycle is up to 21 days
measure: Number of participants with adverse events as a measure safety and tolarability
timeFrame: 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 outcomes:
measure: Tumor response evaluation based on the response criteria as applicable (RECIST v1.1 criteria for solid tumors and revised Lugano Classification for aggressive NHL)
timeFrame: 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)
Other outcomes:
Locations:
city: Springdale
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Silver Spring
country: United States
facility: Maryland Oncology Hematology
state: Maryland
city: Hackensack
country: United States
facility: John Theurer Cancer Center
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute
state: Oregon
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Sioux Falls
country: United States
facility: Avera Health
state: South Dakota
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Austin
country: United States
facility: NEXT Oncology
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: Viña Del Mar
country: Chile
facility: Centro de Investigaciones Clínicas Viña del Mar
state: Valparaíso
city: Viña del Mar
country: Chile
facility: Oncocentro
city: Madrid
country: Spain
facility: START Madrid- Fundación Jiménez Diaz
Study officials:
affiliation: Vincerx Pharma, Inc.
name: Vincerx Study Director
role: STUDY_DIRECTOR
References:
citation: Diamond JR, Boni V, Lim E, Nowakowski G, Cordoba R, Morillo D, Valencia R, Genvresse I, Merz C, Boix O, Frigault MM, Greer JM, Hamdy AM, Huang X, Izumi R, Wong H, Moreno V. First-in-Human Dose-Escalation Study of Cyclin-Dependent Kinase 9 Inhibitor VIP152 in Patients with Advanced Malignancies Shows Early Signs of Clinical Efficacy. Clin Cancer Res. 2022 Apr 1;28(7):1285-1293. doi: 10.1158/1078-0432.CCR-21-3617.