Phase 1
Completed N=15
Phase I/Ib Study of Nivolumab & Veliparib in Patients With Advanced Solid Tumors & Lymphoma
Advanced Solid Neoplasm · Non-Hodgkin's Lymphoma · Recurrent Solid Neoplasm · Mantle Cell Lymphoma
Source: ClinicalTrials.gov NCT03061188 ↗
Enrolled (actual)
15
Serious AEs
100.0%
Results posted
Nov 2020
Primary outcomePrimary: Maximum Tolerated Dose (MTD) — 400 mg
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Tolerated Dose (MTD) |
400 | — |
| SECONDARY Number of Participants With Adverse Events Possibly Related to Study Drugs Graded 3, 4, and 5 |
1; 0; 0; 1; 0; 0 | — |
| SECONDARY ORR (Overall Response Rate) |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Clinical Benefit Rate (CBR) |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Progression Free Survival (PFS) |
2.07; 1.94 | — |
| SECONDARY Overall Survival (OS) |
5.82; 11.79 | — |
| SECONDARY Number of Patients Alive and Progression Free at 24 Weeks |
0; 1; 2 | — |
Eligibility Criteria
Inclusion Criteria
- 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 = = 1.5 x 10^9/L
- Hemoglobin >= 9 g/dL
- Platelets >= 100 x 10^9/L
- Total bilirubin = = 50 mL/min
- Females of child-bearing potential (FOCBP) and men who are sexually active with FOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment and the designated post-treatment period
- NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy
- Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months)
- FOCBP must have a negative pregnancy test = = 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
- Patients who have had a prior severe infusion reaction to a monoclonal antibody are not eligible
- Patients are not eligible who have a history of or active autoimmune disease within the past 3 years with the following exceptions:
- Vitiligo or alopecia
- Hypothyroidism on stable doses of thyroid replacement therapy
- Psoriasis not requiring systemic therapy within the past 3 years
- Patients with a history of primary immunodeficiency disease or tuberculosis are not eligible
- Patients who have an uncontrolled current illness includi
Data sourced from ClinicalTrials.gov (NCT03061188). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.