Last reviewed · How we verify

NCT03061188

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

Completed Phase 1 Results posted Last updated 12 June 2024
What this trial tests

Phase 1 trial testing Laboratory Biomarker Analysis in Advanced Solid Neoplasm in 15 participants. Completed in 4 August 2020.

Timeline
23 May 2017
Primary endpoint
11 March 2018
4 August 2020

Quick facts

Lead sponsorNorthwestern University
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsequential
Maskingnone
Primary purposetreatment
Enrollment15
Start date23 May 2017
Primary completion11 March 2018
Estimated completion4 August 2020
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Northwestern University

Who can join

18 and older, any sex, with Advanced Solid Neoplasm or Aggressive Non-Hodgkin Lymphoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Maximum Tolerated Dose (MTD) Primary · First Cycle of Treatment with velaparib and nivolumab (28 days)

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 withi

GroupValue95% CI
Velaparib PO Twice Daily + Nivolumab (Phase 1)400
Number of Participants With Adverse Events Possibly Related to Study Drugs Graded 3, 4, and 5 Secondary · Up to 30 days after treatment discontinuation, where 1 cycle =28 days, and range of cycles is 1-12.

Toxicity, both frequency and severity, will continue to be measured by monitoring the occurrence of adverse events. Adverse events will be defined as those included in CTCAE v 4.03. AEs that were determined to be at least possibly related to study drug and graded 3, 4, 5 are included here. Grade 1 (mild): the event causes discomfort without disruption of normal daily activities. Grade 2 (moderate): the event causes discomfort that affects normal daily activities. Grade 3 (severe): the event makes the patient unable to perform normal daily activities or significantly affects his/her clinical st

Grade 3 Hypertension
GroupValue95% CI
Phase 1:Cohort 1 (Velaparib 300 mg PO Twice Daily + Nivolumab)1
Phase 1:Cohort 2 (Velaparib 400 mg PO Twice Daily + Nivolumab)0
Phase 2 MTD: Velaparib 400 mg PO Twice Daily + Nivolumab0
Grade 3 Aspartate aminotransferase increased
GroupValue95% CI
Phase 1:Cohort 1 (Velaparib 300 mg PO Twice Daily + Nivolumab)1
Phase 1:Cohort 2 (Velaparib 400 mg PO Twice Daily + Nivolumab)0
Phase 2 MTD: Velaparib 400 mg PO Twice Daily + Nivolumab0
Grade 3 Alanine aminotransferase increased
GroupValue95% CI
Phase 1:Cohort 1 (Velaparib 300 mg PO Twice Daily + Nivolumab)1
Phase 1:Cohort 2 (Velaparib 400 mg PO Twice Daily + Nivolumab)0
Phase 2 MTD: Velaparib 400 mg PO Twice Daily + Nivolumab0
Grade 3 Alkaline phosphatase increased
GroupValue95% CI
Phase 1:Cohort 1 (Velaparib 300 mg PO Twice Daily + Nivolumab)1
Phase 1:Cohort 2 (Velaparib 400 mg PO Twice Daily + Nivolumab)1
Phase 2 MTD: Velaparib 400 mg PO Twice Daily + Nivolumab0
Grade 3 Anemia
GroupValue95% CI
Phase 1:Cohort 1 (Velaparib 300 mg PO Twice Daily + Nivolumab)1
Phase 1:Cohort 2 (Velaparib 400 mg PO Twice Daily + Nivolumab)2
Phase 2 MTD: Velaparib 400 mg PO Twice Daily + Nivolumab0
Grade 4 Anemia
GroupValue95% CI
Phase 1:Cohort 1 (Velaparib 300 mg PO Twice Daily + Nivolumab)0
Phase 1:Cohort 2 (Velaparib 400 mg PO Twice Daily + Nivolumab)1
Phase 2 MTD: Velaparib 400 mg PO Twice Daily + Nivolumab0
Grade 3 Platelet count decreased
GroupValue95% CI
Phase 1:Cohort 1 (Velaparib 300 mg PO Twice Daily + Nivolumab)0
Phase 1:Cohort 2 (Velaparib 400 mg PO Twice Daily + Nivolumab)1
Phase 2 MTD: Velaparib 400 mg PO Twice Daily + Nivolumab0
Grade 3 Fatigue
GroupValue95% CI
Phase 1:Cohort 1 (Velaparib 300 mg PO Twice Daily + Nivolumab)0
Phase 1:Cohort 2 (Velaparib 400 mg PO Twice Daily + Nivolumab)2
Phase 2 MTD: Velaparib 400 mg PO Twice Daily + Nivolumab0
ORR (Overall Response Rate) Secondary · after 2 cycles at first response time point (1 cycle = 28 days)

Overall response rate or ORR, (partial response (PR) + complete response (CR)) will be evaluated using RECIST criteria v1.1 or Lugano 2014 classification for assessment of Lymphoma. Per RECIST v. 1.1: PR= : At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR= Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Per Lugano 2014 classification, scored on a Deauville 5-point scale (an internationally-recommended scale using FDG PET-CT in th

Complete Response
GroupValue95% CI
Velaparib PO Twice Daily + Nivolumab (Cohort 1)0
Velaparib PO Twice Daily + Nivolumab (Cohort 2)0
Velaparib PO Twice Daily + Nivolumab (Phase 2)0
Partial Response
GroupValue95% CI
Velaparib PO Twice Daily + Nivolumab (Cohort 1)0
Velaparib PO Twice Daily + Nivolumab (Cohort 2)0
Velaparib PO Twice Daily + Nivolumab (Phase 2)0
Clinical Benefit Rate (CBR) Secondary · 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.

CBR= stable disease for ≥12 weeks + Partial Response + Complete Response per RECIST v1.1 for solid tumors or Lugano 2014 classification for lymphomas. Lugano scored on a Deauville 5-point scale. RECIST v. 1.1: PR= : At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR= Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the small

Complete Response
GroupValue95% CI
Velaparib PO Twice Daily + Nivolumab (Cohort 1)0
Velaparib PO Twice Daily + Nivolumab (Cohort 2)0
Velaparib PO Twice Daily + Nivolumab (Phase 2)0
Partial Response
GroupValue95% CI
Velaparib PO Twice Daily + Nivolumab (Cohort 1)0
Velaparib PO Twice Daily + Nivolumab (Cohort 2)0
Velaparib PO Twice Daily + Nivolumab (Phase 2)0
Stable Disease for or ≥12 weeks
GroupValue95% CI
Velaparib PO Twice Daily + Nivolumab (Cohort 1)0
Velaparib PO Twice Daily + Nivolumab (Cohort 2)4
Velaparib PO Twice Daily + Nivolumab (Phase 2)2
Progression Free Survival (PFS) Secondary · 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.

To evaluate Progression Free Survival (PFS) for patients treated with nivolumab and veliparib, defined as the time from treatment initiation to documented disease progression. Evaluated by RECIST criteria v1.1 for solid tumors or Lugano 2014 classification for assessment of Lymphoma. RECIST v. 1.1 definition for PD (Progressive disease): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Lugano 2014 classification, scored on a Deauville 5-point scale (an internationally-recommended scale using FDG PET-CT in the initial staging

GroupValue95% CI
Velaparib PO Twice Daily + Nivolumab (Cohort 1)2.072.00 – NA
Velaparib PO Twice Daily + Nivolumab (Cohort 2 + Phase 2)1.941.77 – NA
Overall Survival (OS) Secondary · From the start of treatment and up to 3 years, where 1 cycle =28 days, and range of cycles is 1-12.

Overall Survival is defined as the time from treatment initiation until death due to any cause, assessed up to 3 years from the start of treatment.

GroupValue95% CI
Velaparib PO Twice Daily + Nivolumab (Cohort 1)5.824.73 – NA
Velaparib PO Twice Daily + Nivolumab (Cohort 2 + Phase 2)11.796.18 – NA
Number of Patients Alive and Progression Free at 24 Weeks Secondary · At 24 weeks

To evaluate the number of patients alive and progression free at 24 weeks. -Per RECIST v. 1.1 (for solid tumors) progression is defined as : At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression.) -Lugano 2014 classification, scored on a Deauville 5-point scale (an internationall

GroupValue95% CI
Velaparib PO Twice Daily + Nivolumab (Cohort 1)0
Velaparib PO Twice Daily + Nivolumab (Cohort 2)1
Velaparib PO Twice Daily + Nivolumab (Phase 2)2

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events (AEs) were collected over a 3 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 28 days the range of cycles attempted was 1-12.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Phase 1:Cohort-1 (Velaparib 200 mg PO Twice Daily + Nivolumab)
Serious: 0
Deaths: 0
Phase 1:Cohort 1 (Velaparib 300 mg PO Twice Daily + Nivolumab)
Serious: 3/3 (100%)
Deaths: 3/3
Phase 1:Cohort 2 (Velaparib 400 mg PO Twice Daily + Nivolumab)
Serious: 6/6 (100%)
Deaths: 6/6
Phase 2 MTD: Velaparib 400 mg PO Twice Daily + Nivolumab
Serious: 6/6 (100%)
Deaths: 5/6

Serious adverse events (14 terms)

ReactionSystemPhase 1:Cohort-1 (Velapari…Phase 1:Cohort 1 (Velapari…Phase 1:Cohort 2 (Velapari…Phase 2 MTD: Velaparib 400…
SepsisInfections and infestations
Disease progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)
FeverGeneral disorders
Hepatobiliary disorder - Other:CholangitisHepatobiliary disorders
GI bleedGastrointestinal disorders
Hepatic InfectionInfections and infestations
Gastric outlet obstructionGastrointestinal disorders
PericarditisCardiac disorders
Gastric HemorrhageGastrointestinal disorders
Cardiac ArrestCardiac disorders
Abdominal painGastrointestinal disorders
Movements InvoluntaryNervous system disorders
DiarrheaGastrointestinal disorders
Pleural EffusionRespiratory, thoracic and mediastinal disorders
Other adverse events (88 terms — click to expand)

ReactionSystemPhase 1:Cohort-1 (Velapari…Phase 1:Cohort 1 (Velapari…Phase 1:Cohort 2 (Velapari…Phase 2 MTD: Velaparib 400…
Alkaline phosphatase increasedInvestigations
AnemiaBlood and lymphatic system disorders
DizzinessNervous system disorders
Lymphocyte count decreasedInvestigations
Aspartate aminotransferase increasedInvestigations
FatigueGeneral disorders
HypoalbuminemiaMetabolism and nutrition disorders
NauseaGastrointestinal disorders
Platelet count decreasedInvestigations
Weight lossInvestigations
Abdominal painGastrointestinal disorders
AnxietyPsychiatric disorders
Blood bilirubin increasedInvestigations
ConstipationGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
HypertensionVascular disorders
InsomniaPsychiatric disorders
VomitingGastrointestinal disorders
AnorexiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
Blurred visionEye disorders
DiarrheaGastrointestinal disorders
Edema limbsGeneral disorders
FeverGeneral disorders
FlatulenceGastrointestinal disorders
HyperglycemiaMetabolism and nutrition disorders
HypokalemiaMetabolism and nutrition disorders
HyponatremiaMetabolism and nutrition disorders
HypophosphatemiaMetabolism and nutrition disorders
MyalgiaMusculoskeletal and connective tissue disorders
Abdominal distensionGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
Allergic rhinitisRespiratory, thoracic and mediastinal disorders
Anal hemorrhageGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
AscitesGastrointestinal disorders
Chest wall painMusculoskeletal and connective tissue disorders
ChillsGeneral disorders
Chronic kidney diseaseRenal and urinary disorders
ConfusionPsychiatric disorders

Most-reported serious reactions: Sepsis, Disease progression, Fever, Hepatobiliary disorder - Other:Cholangitis, GI bleed, Hepatic Infection, Gastric outlet obstruction, Pericarditis.

Data from ClinicalTrials.gov NCT03061188 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Alterations of DNA damage response pathway: Biomarker and therapeutic strategy for cancer immunotherapy.
    Jiang M, Jia K, Wang L, Li W, et al · · 2021 · cited 236× · PMID 34729299 · DOI 10.1016/j.apsb.2021.01.003
  2. Combining DNA damaging therapeutics with immunotherapy: more haste, less speed.
    Brown JS, Sundar R, Lopez J. · · 2018 · cited 178× · PMID 29123260 · DOI 10.1038/bjc.2017.376
  3. Combined PARP Inhibition and Immune Checkpoint Therapy in Solid Tumors.
    Peyraud F, Italiano A. · · 2020 · cited 163× · PMID 32526888 · DOI 10.3390/cancers12061502
  4. PARP inhibitors: Clinical utility and possibilities of overcoming resistance.
    Bitler BG, Watson ZL, Wheeler LJ, Behbakht K. · · 2017 · cited 161× · PMID 29037806 · DOI 10.1016/j.ygyno.2017.10.003
  5. Targeting DNA repair pathway in cancer: Mechanisms and clinical application.
    Wang M, Chen S, Ao D. · · 2021 · cited 84× · PMID 34977872 · DOI 10.1002/mco2.103
  6. The role of DNA damage repair (DDR) system in response to immune checkpoint inhibitor (ICI) therapy.
    Shi C, Qin K, Lin A, Jiang A, et al · · 2022 · cited 60× · PMID 36071479 · DOI 10.1186/s13046-022-02469-0
  7. Immunomodulatory Roles of PARP-1 and PARP-2: Impact on PARP-Centered Cancer Therapies.
    Yélamos J, Moreno-Lama L, Jimeno J, Ali SO. · · 2020 · cited 56× · PMID 32046278 · DOI 10.3390/cancers12020392
  8. Homologous Recombination Repair Deficiency and the Immune Response in Breast Cancer: A Literature Review.
    Pellegrino B, Musolino A, Llop-Guevara A, Serra V, et al · · 2020 · cited 56× · PMID 31901781 · DOI 10.1016/j.tranon.2019.10.010

Verify or expand the search:

Other trials of Laboratory Biomarker Analysis

Trials testing the same drug.

Other Northwestern University trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03061188.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing