Phase I/Ib Study of Nivolumab & Veliparib in Patients With Advanced Solid Tumors & Lymphoma

NCT03061188 | Completed Phase 1 Results DMC FDA Drug

• 4 other identifiers: NU 16MH03STU00204250P30CA060553NCI-2016-02018
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to determine the highest and safest dose of the experimental drug veliparib when combined with nivolumab. We will also study how safely this combination of medication can be given in advanced cancer and lymphoma and benefits of receiving this therapy. Nivolumab is currently approved in certain cancers such as melanoma, lung cancer and kidney cancer. Veliparib is not yet approved for use in the United States, and is considered experimental. Veliparib inhibits (blocks) the activity of the enzyme PARP. This blocking activity may prevent the cancer cell from repairing itself and resume growing. Nivolumab increases T cells in your immune system, which allows your immune system to attack the cancer. We think the combination of these drugs will be more effective against your cancer.

Conditions

Advanced Solid Neoplasm; Aggressive Non-Hodgkin Lymphoma; Recurrent Solid Neoplasm; Refractory Mantle Cell Lymphoma; T-Cell Non-Hodgkin Lymphoma; Unresectable Solid Neoplasm

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  The MTD will be defined as the highest dose that causes dose-limiting toxicities (DLTs) in \<2 of 6 patients. Toxicity will be assessed using CTCAEv4.03. A DLT is defined as an Adverse Event (AE) or abnormal laboratory value assessed as at least possibly related to the study medication, occurs ≤ 28 days (1 cycle) following the first dose of veliparib and nivolumab and meets any of the following criteria: Grade ≥ 3 non-hematologic toxicities that represent at least a 2-grade increase from baseline excluding Nausea, vomiting, diarrhea lasting ≤48 hours, Electrolyte abnormalities resolving within ≤24 hours, Hypersensitivity reactions,and Alopecia. Grade 4 thrombocytopenia (platelets \< 25.0 x 109 /L) Grade 3 thrombocytopenia with bleeding (platelets \< 0.5 x 109 /L) 5. Grade 3 febrile neutropenia with fever lasting for \> 7 days 6. Grade 4 febrile neutropenia of any duration 7. Dosing delay due to toxicity for \> 14 consecutive days from the date nivolumab or veliparib is due.

  First Cycle of Treatment with velaparib and nivolumab (28 days)

Secondary Outcomes (6)

• Number of Participants With Adverse Events Possibly Related to Study Drugs Graded 3, 4, and 5

  Up to 30 days after treatment discontinuation, where 1 cycle =28 days, and range of cycles is 1-12.

• ORR (Overall Response Rate)

  after 2 cycles at first response time point (1 cycle = 28 days)

• Clinical Benefit Rate (CBR)

  From the start of treatment and every 2 cycles during treatment where 1 cycle =28 days, average number of cycles is 4 and range of cycles is 1-12.

• Progression Free Survival (PFS)

  From the start of treatment and every 2 cycles during treatment, and up to three years, where 1 cycle =28 days, and range of cycles is 1-12.

• Overall Survival (OS)

  From the start of treatment and up to 3 years, where 1 cycle =28 days, and range of cycles is 1-12.

Study Arms (1)

Treatment (veliparib, nivolumab)

EXPERIMENTAL

Patients receive veliparib PO BID on day 1 and nivolumab IV over 30 minutes on days 1 and 15 of courses 1-4 and IV over 60 minutes on day 1 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Other: Pharmacological Study; Drug: Veliparib

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (veliparib, nivolumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Treatment (veliparib, nivolumab)

Pharmacological Study OTHER

Correlative studies

Treatment (veliparib, nivolumab)

Veliparib DRUG

Given PO

Also known as: ABT-888, PARP-1 inhibitor ABT-888

Treatment (veliparib, nivolumab)

Eligibility Criteria

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

You may qualify if:

• Patients must have a histologically documented (either primary or metastatic site) diagnosis of advanced solid tumor cancer (stage IV or unresectable) or aggressive lymphoma (diffuse large B cell lymphoma, mantle cell lymphoma, T cell lymphoma, and natural killer \[NK\] cell lymphoma)
• NOTE: The following histologies will be excluded given known response to PD-1/PD-L1 inhibitor monotherapy: non-small cell lung cancer, squamous cell carcinoma of head and neck, melanoma, renal cell carcinoma, bladder cancer, Hodgkin's lymphoma, Merkel cell carcinoma, and high-frequency microsatellite instability (MSI-H) colorectal cancer
• All patients must have received, and be relapsed/refractory to at least one line of systemic therapy
• NOTE: This does not include surgery or radiation alone; patients may have received any number of systemic therapies
• All patients with relapsed/refractory lymphoma must have received or be ineligible for autologous stem cell transplant or be ineligible for allogeneic stem cell transplant
• NOTE: Patients must not have had a prior allogeneic stem cell transplant
• Patients must have measurable disease as per appropriate guidelines:
• Solid tumors: by RECIST v1.1
• Lymphoma: patient has at least one measurable nodal lesion (\>= 2 cm) according to Lugano classification; if the patient has no measurable nodal lesions \>= 2 cm in the long axis at screening, then the patient must have at least one measurable extra-nodal lesion
• Patients must have the ability to understand and the willingness to sign a written consent prior to registration in the study
• For expansion cohort patients, the profiling must reveal at least one mutation in the following selected DNA repair genes involved in cell cycle arrest signal transduction, BRCA1 pathway, Fanconi's proteins pathway, and RAD51 pathway: (ATR, ATM, CHEK1, CHEK2, BRCA1, BAP1, BARD1, FANCD2, FANCE, FANCC, RAD50, FANCA, RAD51, BRCA2, PALB2, CDK12 \[ENSG00000167258, also known as CRK7, CRKR, CRKRS\], POLE, POLD1, BRAC2, PRKDC, ERCC2, POLQ, MRE11A, NBN \[MBS1\]), or at least one gene amplification in FANCD2, FANCE, FANCC, FANCA, C11orf30 (EMSY)
• NOTE: Tissue or blood cell free DNA are allowed for genomic profiling of tumor; profiling should have been performed at a Clinical Laboratory Improvement Act (CLIA) certified lab =\< 1 year prior to registration
• NOTE: Patients in the dose escalation phase are not required to have such mutations; although genomic profiling is not required for dose escalation patients, it is encouraged in these patients prior to or after study registration if feasible
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2
• Patients must have adequate organ and bone marrow function =\< 14 days prior to registration, as defined below (Note: blood transfusion or growth factors is not permitted within 14 days of registration):

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy =\< 14 days prior to entering the study are not eligible
• NOTE: Patients may not have had systemic chemotherapy within 28 days
• Patients are not eligible who have had major surgery =\< 14 days of registration; please contact principle investigator (PI) and quality assurance monitor (QAM) for questions about specific surgical procedures
• Patients are not eligible who have received prior PARP inhibitors (including but not limited to veliparib, talazoparib, rucaparib, and olaparib)
• Patients are not eligible who have received systemic chemotherapy or investigational agents =\< 28 days prior to registration
• Patients are not eligible who have received prior immunotherapy including interleukin-2 and immune checkpoint antagonists and/or agonists (including but not limited to PD-1, PD-L1, CD137, or OX40)
• NOTE: Single agent anti-CTLA4 monoclonal antibody treatments are permitted; cancer vaccine therapies are permitted
• Patients with the following histologies are not eligible for either study cohort given known response to PD-1/PD-L1 inhibitor monotherapy:
• Non-small cell lung cancer, squamous cell carcinoma of head and neck, melanoma, renal cell carcinoma, bladder cancer, Hodgkin's lymphoma, Merkel cell carcinoma, and MSI-H colorectal cancer
• Patients are not eligible who have had a prior allogeneic stem cell transplant
• NOTE: Autologous stem cell transplant is acceptable
• Patients who are taking any herbal (alternative) medicines are NOT eligible for participation; patients must be off any such medications by the time of registration for \>= 14 days
• NOTE: Vitamin supplements are acceptable
• Patients must have no history of central nervous system (CNS) metastasis at the screening assessment
• NOTE: Patients with stable brain metastases (mets) which have been treated are eligible; patients with suspected symptoms of CNS metastasis should undergo CNS imaging at the time of screening to rule out active metastasis

Sponsors & Collaborators

• Northwestern University: lead
• Bristol-Myers Squibb: collaborator
• AbbVie: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Lymphoma, Mantle-Cell; Lymphoma, T-Cell

Interventions

Nivolumab; veliparib

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

The original accrual goal was 50 patients. Due to funding issues the accrual goal was reduced to 15 patients.

Results Point of Contact

• Title: Young Kwang Chae, MD, MPH, MBA
• Organization: Northwestern University, Feinberg School of Medicine

YCHAE@nm.org

312-926-4248

Study Officials

• Young K. Chae, MD, MPH, MBA

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 17, 2017
• First Posted: February 23, 2017
• Study Start: May 23, 2017
• Primary Completion: March 11, 2018
• Study Completion: August 4, 2020
• Last Updated: June 12, 2024
• Results First Posted: November 19, 2020

Record last verified: 2024-05

Locations

US (1)