Niraparib + Ipilimumab or Nivolumab in Progression Free Pancreatic Adenocarcinoma After Platinum-Based Chemotherapy

NCT03404960 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 828516
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to look at the effectiveness, safety, and anti-tumor activity (preventing growth of the tumor) of the drugs Niraparib with either Ipilimumab or Nivolumab on patients and their pancreatic cancer.

Conditions

Pancreatic Adenocarcinoma

Keywords

Platinum; chemotherapy; Niraparib; Ipilimumab; Nivolumab; Pancreatic adenocarcinoma; PARP inhibitor; Pancreatic ductal adenocarcinoma; DDR; PDAC

Outcome Measures

Primary Outcomes (1)

• Rate of Progression-free Survival at 6 Months (PFS6)

  The PFS6 rate will be estimated using the Kaplan-Meier method, and the 95% confidence interval will be estimated from the Kaplan-Meier curve. The null hypothesis is that the PFS6 rate in this population of subjects is 44%. Progressive disease is defined as at least a 20% increase in the sum of all the longest diameter (LD) 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 5mm. The appearance of one or more new lesions is also considered progression. Target lesions assessed according to RECIST v1.1.

  6 months after initiation of study therapy

Secondary Outcomes (2)

• Objective Response Rate (ORR) Per RECIST v.1.1 as Assessed by Radiology Review

  From first restaging assessment through completion of study treatment (maximum 42 months)

• Overall Survival (OS)

  Cycle 1 Day 1 until death, loss to follow-up, withdrawal of consent or until 5 years have passed, whichever occurs first

Study Arms (2)

Arm A

EXPERIMENTAL

Niraparib + Nivolumab

Drug: Niraparib + Nivolumab

Arm B

EXPERIMENTAL

Niraparib + Ipilimumab

Drug: Niraparib + Ipilimumab

Interventions

Niraparib + Nivolumab DRUG

Niraparib 200mg PO daily on days 1-28 of each 28-day cycle. Nivolumab 480mg IV day 1 of each cycle.

Also known as: Arm A

Arm A

Niraparib + Ipilimumab DRUG

Niraparib 200mg PO daily on days 1-21 of each 21-day cycle. Ipilimumab 3mg/kg IV day 1 of each cycle, for the first 4 cycles only.

Also known as: Arm B

Arm B

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma with locally advanced or metastatic disease
• ≥18 years of age
• Patients must be able to understand the study procedures and agree to participate in the study by providing written informed consent
• Patients must have received treatment with platinum-based (cisplatin, oxaliplatin or carboplatin) treatment for locally advanced or metastatic pancreatic cancer and have received a minimum of 16 weeks of therapy without evidence of disease progression based on the investigator's opinion. This does not have to be the patient's current treatment.
• This requires at least stable imaging and a stable or decreasing tumor marker as applicable and as determined by the investigator.
• If a patient has demonstrated a biochemical and imaging response to platinum therapy and has not progressed within 16 weeks of starting this therapy but had to discontinue platinum prior to 16 weeks for a legitimate medical reason (as determined by the investigator), the patient may still be considered for the trial
• Patients may have previously failed non-platinum containing therapy or may never have previously progressed on treatment
• Discontinuation of the platinum component of the regimen for chemotherapy-related toxicity is permissible provided the patient has previously received at least 16 weeks of platinum-based therapy without evidence of disease progression ≤8 weeks after treatment with the platinum agent
• Measurable disease is not a requirement for study entry
• Female participant has a negative serum pregnancy test within 24 hours prior to taking study treatment if of childbearing potential and agrees to abstain from activities that could result in pregnancy from screening through 6 months after the last dose of study treatment, or is of nonchildbearing potential
• Male patient agrees to use an adequate method of contraception starting with the first dose through 90 days after the last dose of study treatment
• Adequate organ function confirmed by the following laboratory values obtained ≤7 days prior to the first day of study therapy:
• Absolute neutrophil count (ANC) ≥1.5 x 109/L
• Platelets\>100 x 109/L
• Hemoglobin ≥9g/dL

You may not qualify if:

• Prior treatment with a PARP inhibitor, ipilimumab, nivolumab or other cytotoxic T-lymphocyte-associated protein (CTLA-4), PD-1 or PD-L1 inhibitor.
• Patients who have demonstrated resistance to platinum agents (e.g. oxaliplatin, cisplatin) are not eligible to participate in this study
• Clinical evidence of uncontrolled malabsorption and/or any other gastrointestinal disorder or defect that would, in the opinion of the investigator, interfere with the absorption of niraparib
• Acute infection requiring intravenous antibiotics, antiviral or antifungal agents during the 14 days prior to first dose of study therapy
• Patients will be excluded if they have an active, known or suspected autoimmune disease, defined as: patients with a history of inflammatory bowel disease are excluded from this study, as are patients with a history of symptomatic autoimmune disease (e.g. rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus, autoimmune vasculitis e.g. Wegener's Granulomatosis); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome).
• NOTE: Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
• Has a history of interstitial lung disease or active, non-infectious pneumonitis
• Has received a live vaccine within 4 weeks prior to the first dose of trial therapy (Note: seasonal influenza vaccines for injection are generally inactivated and are allowed; however intranasal influenza vaccines (e.g. Flu-Mist) are live attenuated vaccines and are not allowed
• For fertile patient (female able to become pregnant or male able to father a child), refusal to use effective contraception during the period of the trial and:
• Female patients refusing to use effective contraception for 6 months after the last dose of study drug.
• Male patients refusing to use effective contraception for 90 days after the last dose of study drug.
• Received any systemic treatment for pancreatic cancer ≤14 days prior to first dose of therapy. Patients must not have had investigational therapy administered ≤4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is longer, prior to the first scheduled day of dosing in this study
• Patients will be excluded if they have a condition requiring systemic treatment with either corticosteroids (\>10mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \>10mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Patient has had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted \> 4 weeks and was related to the most recent treatment.
• Non-study related minor surgical procedure ≤5 days, or major surgical procedure ≤21 days, prior to the first dose of therapy; in all cases, patients must be sufficiently recovered and stable before treatment administration.

Sponsors & Collaborators

• University of Pennsylvania: lead
• Bristol-Myers Squibb: collaborator
• GlaxoSmithKline: collaborator

Study Sites (1)

University of Pennsylvania, Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Reiss KA, Mick R, Teitelbaum U, O'Hara M, Schneider C, Massa R, Karasic T, Tondon R, Onyiah C, Gosselin MK, Donze A, Domchek SM, Vonderheide RH. Niraparib plus nivolumab or niraparib plus ipilimumab in patients with platinum-sensitive advanced pancreatic cancer: a randomised, phase 1b/2 trial. Lancet Oncol. 2022 Aug;23(8):1009-1020. doi: 10.1016/S1470-2045(22)00369-2. Epub 2022 Jul 7.

  PMID: 35810751 DERIVED

MeSH Terms

Interventions

niraparib; Nivolumab; Ipilimumab

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Regulatory Lead
• Organization: University of Pennsylvania

psom-ind-ide@pobox.upenn.edu

215-662-4484

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: December 19, 2017
• First Posted: January 19, 2018
• Study Start: January 31, 2018
• Primary Completion: April 5, 2022
• Study Completion: October 9, 2024
• Last Updated: October 10, 2025
• Results First Posted: July 3, 2023

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

US (1)