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

NCT02635672 | Completed Phase 1 FDA Drug

• 2 other identifiers: VNC-152-1012014-004808-30
• Study Type: interventional
• Target: 110
• Locations: 3 countries
• Sites: 16

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).

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

Outcome Measures

Primary Outcomes (10)

• 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 Outcomes (1)

• 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)

Study Arms (4)

Dose escalation of VIP152 (BAY 1251152) / PART 1 (Completed)

EXPERIMENTAL

Investigating VIP152 (BAY 1251152) in a dose escalation cohort in patients with solid tumors and aggressive NHL

Drug: VIP152 (BAY 1251152)

Dose expansion of VIP152 (BAY 1251152) / PART 2

EXPERIMENTAL

Investigating VIP152 (BAY 1251152) in a dose expansion cohort in patients with solid tumors and aggressive NHL

Drug: VIP152 (BAY 1251152) 30 mg

Dose escalation of VIP152 (BAY 1251152) in combination with Keytruda® (pembrolizumab) / PART 3

EXPERIMENTAL

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; Drug: VIP152 (BAY 1251152) 15 mg

Dose expansion of VIP152 (BAY 1251152) in combination with Keytruda® (pembrolizumab) / PART 4

EXPERIMENTAL

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; Drug: Keytruda

Interventions

VIP152 (BAY 1251152) DRUG

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.

Dose escalation of VIP152 (BAY 1251152) / PART 1 (Completed)

VIP152 (BAY 1251152) 30 mg DRUG

30 mg IV (30 minute infusion) fixed dose once weekly of a 21 day cycle.

Dose expansion of VIP152 (BAY 1251152) / PART 2; Dose expansion of VIP152 (BAY 1251152) in combination with Keytruda® (pembrolizumab) / PART 4

Keytruda DRUG

200 mg IV fixed dose once every 3 weeks of a 21 day cycle

Also known as: pembrolizumab

Dose escalation of VIP152 (BAY 1251152) in combination with Keytruda® (pembrolizumab) / PART 3; Dose expansion of VIP152 (BAY 1251152) in combination with Keytruda® (pembrolizumab) / PART 4

VIP152 (BAY 1251152) 15 mg DRUG

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.

Dose escalation of VIP152 (BAY 1251152) in combination with Keytruda® (pembrolizumab) / PART 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Vincerx Pharma, Inc.: lead

Study Sites (16)

Highlands Oncology Group

Springdale, Arkansas, 72762, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40202, United States

Location

Maryland Oncology Hematology

Silver Spring, Maryland, 20904, United States

Location

John Theurer Cancer Center

Hackensack, New Jersey, 07601, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

Willamette Valley Cancer Institute

Eugene, Oregon, 97401, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Avera Health

Sioux Falls, South Dakota, 57105, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

NEXT Oncology

Austin, Texas, 78758, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

Centro de Investigaciones Clínicas Viña del Mar

Viña del Mar, Región de Valparaíso, 2540364, Chile

Location

Oncocentro

Viña del Mar, 2520598, Chile

Location

START Madrid- Fundación Jiménez Diaz

Madrid, 28040, Spain

Location

Related Publications (1)

• 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.

  PMID: 35046056 DERIVED

Related Links

• Click here and search for information on any recalls, market or product safety alerts by the FDA which might have occurred with this product.

MeSH Terms

Conditions

Neoplasms; Triple Negative Breast Neoplasms; Prostatic Neoplasms; Melanoma; Carcinoma, Non-Small-Cell Lung; Esophageal Neoplasms; Carcinoma, Transitional Cell; Stomach Neoplasms; Uterine Cervical Neoplasms; Carcinoma, Hepatocellular; Carcinoma, Merkel Cell; Carcinoma, Renal Cell; Endometrial Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Stomach Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Adenocarcinoma; Liver Neoplasms; Liver Diseases; Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Kidney Neoplasms; Urologic Neoplasms; Kidney Diseases; Urologic Diseases

Study Officials

• Vincerx Study Director

  Vincerx Pharma, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2015
• First Posted: December 21, 2015
• Study Start: February 10, 2016
• Primary Completion: November 11, 2024
• Study Completion: November 11, 2024
• Last Updated: November 15, 2024

Record last verified: 2024-11

Locations

CL (2); ES (1); US (13)