BMS-813160 With Nivolumab and Gemcitabine and Nab-paclitaxel in Borderline Resectable and Locally Advanced Pancreatic Ductal Adenocarcinoma (PDAC)

NCT03496662 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 2018060071P50CA196510-01A1
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to learn more about a new combination of drugs being given to treat pancreatic cancer. The drugs being tested are BMS-813160, nivolumab, gemcitabine, and nab-paclitaxel. The investigators will be looking at both the side effects and the way the disease responds to treatment.

Conditions

Pancreatic Ductal Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• (Part A Experimental Dose Level 0 Only) Safety of the Combination of BMS-813160 Plus Nivolumab Plus Gemcitabine Plus Nab-paclitaxel as Measured by Frequency, Type, and Severity of Adverse Events

  -The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for all toxicity reporting.

  Through 100 days after completion of treatment (approximately 7.5 months)

• (Part B and Part A Experimental Dose Level 0 Only): Objective Response Rate

  * Objective response rate (ORR) is defined as number of participants with complete response or partial response. * Complete Response (CR): Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Normalization of tumor marker level. * Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  Through completion of treatment (approximately 4 months)

Secondary Outcomes (3)

• (Part B and Part A Experimental Dose Level 0 Only): Percentage of Patients Whose Disease Becomes Resectable After Treatment

  Completion of treatment (approximately 4 months)

• (Part B and Part A Experimental Dose Level 0 Only): Progression-free Survival (PFS)

  Through completion of follow-up (median length of follow-up 12.15 months, full range 0.43-44.10 months)

• (Part B and Part A Experimental Dose Level 0 Only): Overall Survival (OS)

  Through completion of follow-up (median length of follow-up 17.63 months, full range 0.43-64.47 months)

Study Arms (3)

Part A - Experimental Dose Level 0

EXPERIMENTAL

* BMS-813160 300 mg twice per day * Nivolumab 30-minute intravenous (IV) infusion at a flat dose of 480 mg on Day 1 of each 28-day cycle * Gemcitabine 30-minute IV infusion 1000 mg/m\^2 on Days 1, 8, and 15 of each 28-day cycle * Nab-paclitaxel 30-40-minute IV infusion 125 mg/m\^2 on Days 1, 8, and 15 of each 28-day cycle * Post-treatment biopsy at the end of cycle 2 * Patients who achieve stable disease, a partial response, or complete response after the first 2 cycles of treatment will continue to receive 2 more cycles of treatment followed by a restaging scan. Patients thought to have pseudo-progression will continue to receive treatment for 2 more cyclesore cycles

Drug: BMS-813160; Drug: Nivolumab; Drug: Gemcitabine; Drug: Nab-paclitaxel; Procedure: Biopsy; Procedure: Peripheral blood

Part A - Control (chemotherapy only)

ACTIVE COMPARATOR

* Gemcitabine 30-minute IV infusion 1000 mg/m\^2 on Days 1, 8, and 15 of each 28-day cycle Nab-paclitaxel 30-40-minute IV infusion 125 mg/m\^2 on Days 1, 8, and 15 of each 28-day cycle * Post treatment biopsy at the end of cycle 2 * Patients who achieve stable disease, a partial response, or complete response after the first 2 cycles of treatment will continue to receive 2 more cycles of treatment followed by a restaging scan. Patients thought to have pseudo-progression will continue to receive treatment for 2 more cycles

Drug: Gemcitabine; Drug: Nab-paclitaxel; Procedure: Biopsy; Procedure: Peripheral blood

Part B - Dose expansion

EXPERIMENTAL

* BMS-813160 300 mg twice per day * Nivolumab 30-minute IV infusion at a flat dose of 480 mg on Day 1 of each 28-day cycle * Gemcitabine 30-minute IV infusion 1000 mg/m\^2 on Days 1, 8, and 15 of each 28-day cycle * Nab-paclitaxel 30-40-minute IV infusion 125 mg/m\^2 on Days 1, 8, and 15 of each 28-day cycle * Post-treatment biopsy at the end of cycle 2 * Patients who achieve stable disease, a partial response, or complete response after the first 2 cycles of treatment will continue to receive 2 more cycles of treatment followed by a restaging scan. Patients thought to have pseudo-progression will continue to receive treatment for 2 more cycles

Drug: BMS-813160; Drug: Nivolumab; Drug: Gemcitabine; Drug: Nab-paclitaxel; Procedure: Biopsy; Procedure: Peripheral blood

Interventions

BMS-813160 DRUG

BMS-813160 will be supplied by Bristol Myers Squibb

Part A - Experimental Dose Level 0; Part B - Dose expansion

Nivolumab DRUG

Nivolumab will be supplied by Bristol Myers Squibb

Also known as: Opdivo

Part A - Experimental Dose Level 0; Part B - Dose expansion

Gemcitabine DRUG

Gemcitabine will be given as per routine care from commercial supply.

Also known as: Gemzar

Part A - Control (chemotherapy only); Part A - Experimental Dose Level 0; Part B - Dose expansion

Nab-paclitaxel DRUG

Nab-paclitaxel will be given as per routine care from commercial supply.

Also known as: Abraxane

Part A - Control (chemotherapy only); Part A - Experimental Dose Level 0; Part B - Dose expansion

Biopsy PROCEDURE

Pre-treatment, end of cycle 2, end of treatment for patients who progress or otherwise do not go to surgery, and surgery for patients who do go to surgery

Part A - Control (chemotherapy only); Part A - Experimental Dose Level 0; Part B - Dose expansion

Peripheral blood PROCEDURE

-Cycle 1 Day 1 before treatment begins, after 2 cycles of treatment +/- 3 days of mandatory tumor biopsy, end of treatment for patients who progress or otherwise do not go to surgery, and no more than 24 hours prior to time of surgery (if applicable)

Part A - Control (chemotherapy only); Part A - Experimental Dose Level 0; Part B - Dose expansion

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 locally advanced or borderline resectable pancreatic ductal adenocarcinoma. Patients with clinical suspicion of pancreatic adenocarcinoma can be enrolled for pre-treatment biopsy, and must be histologically confirmed to have adenocarcinoma before being treated on study. Patients with squamous carcinoma, adenosquamous carcinoma or neuroendocrine tumor will be excluded. Tumor Biopsy can be omitted, if deemed by PI and treatment physician, that it may incur immediate, excessive health risks to patients. This determination (rationale and discussion with PI and treating physician) should be clearly documented in the screening visit notes.
• Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan or MRI.
• At least 18 years of age.
• ECOG performance status ≤ 1
• Normal bone marrow and organ function as defined below:
• Leukocytes ≥ 2,000/mcL
• Absolute neutrophil count ≥ 1,500/mcl
• Hemoglobin ≥ 8.5 g/dL
• Platelets ≥ 100,000/mcl
• Total bilirubin ≤ 1.5 x IULN (except participants with Gilbert's Syndrome who must have normal direct bilirubin)
• AST(SGOT)/ALT(SGPT) ≤ 3 x IULN
• Serum albumin ≥ 3g/dL
• Creatinine ≤ 1.5 x IULN OR creatinine clearance ≥ 40 mL/min by Cockcroft-Gault for patients with creatinine levels above institutional normal
• Women of childbearing potential and men must agree to use at least two forms of contraception (hormonal, barrier method of birth control, abstinence, and must include barrier method) prior to study entry, for the duration of study participation, and through 5 months (for women) or 7 months (for men) after the last dose of treatment on this study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
• Able to understand and willing to sign an IRB approved written informed consent document.

You may not qualify if:

• Prior exposure to chemotherapy or radiation for the disease to be treated on this trial not allowed.
• Previous malignancies (except non-melanoma skin cancers, and in situ bladder, gastric, colorectal, endometrial, cervical/dysplasia, melanoma, or breast cancers) unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period. Other active malignancy requiring concurrent intervention
• Currently receiving any other investigational agents, or exposure to any investigational drug or placebo within 4 weeks of study treatment
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to BMS-813160, nivolumab, gemcitabine, paclitaxel, nab-paclitaxel, or other agents used in the study.
• Prior exposure to anti-PD-1, anti-PD-L1, CCR2/5, or anti-CTLA4 antibodies.
• Taking immunomodulatory agents (including steroids and NSAIDs). A wash-out period of at least 4 weeks or 5 half-lives, whichever is shorter, is required for patients receiving immunomodulatory agents at the time of enrollment.
• Note: daily use of low dose aspirin (e.g. 81 mg PO QD) is not considered an immunomodulatory agent and patients are still eligible for enrollment despite taking such medication at a low dose
• Participants with active, known or suspected autoimmune disease. Participants with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, euthyroid participants with a history of Grave's disease (participants with suspected autoimmune thyroid disorders must be negative for thyroglobulin and thyroid peroxidase antibodies and thyroid stimulating immunoglobulin prior to first dose of study treatment), psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll after discussing with the Principal Investigator
• Participants with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study treatment except for adrenal replacement steroid doses \> 10 mg daily prednisone equivalent in the absence of active autoimmune disease. Note: treatment with a short course of steroids (\< 5 days) up to 7 days prior to initiating study treatment is permitted.
• History of allogeneic organ or stem cell transplant.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry and again within 24 hours prior to first treatment.
• Known history of hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or known active hepatitis C virus (by PCR).
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome. Anti-retroviral agents are known to have potential adverse pharmacokinetic interactions with nivolumab and/or BMS-813160. IN addition, patients not on anti-retroviral agents, regardless of HIV viral load, are at increased risk of lethal infections with marrow-suppressive therapy including chemotherapy. Testing for HIV must be performed at sites mandated by local requirements.
• Requires continued use of warfarin for anticoagulation and cannot stop warfarin or be safely switched to another anticoagulant.
• Current or recent (within 3 months of study treatment administration) gastrointestinal disease or conditions that could interfere with the swallowing or absorption of study medication or inability to tolerate oral medication.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Bristol-Myers Squibb: collaborator
• The Foundation for Barnes-Jewish Hospital: collaborator
• National Institutes of Health (NIH): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Interventions

BMS-813160; Nivolumab; Gemcitabine; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Biopsy

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Kian-Huat Lim, M.D., Ph.D.
• Organization: Washington University School of Medicine

kian-huat.lim@wustl.edu

314-362-6157

Study Officials

• Kian-Huat Lim, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Model Details: Part A: 16 patients will be randomized to 1:1 to control or experimental arm through block randomization without stratification factors. After 8 evaluable patients have been enrolled and treated on the control arm, subsequent patients are enrolled only into the experimental arm.

Study Record Dates

• First Submitted: April 5, 2018
• First Posted: April 12, 2018
• Study Start: August 31, 2018
• Primary Completion: October 28, 2021
• Study Completion: July 25, 2024
• Last Updated: July 29, 2025
• Results First Posted: November 30, 2022

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)