Safety and Efficacy of APX005M With Gemcitabine and Nab-Paclitaxel With or Without Nivolumab in Patients With Previously Untreated Metastatic Pancreatic Adenocarcinoma

NCT03214250 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: PICI0002UPCC 11217
• Study Type: interventional
• Target: 129
• Locations: 1 country
• Sites: 7

Brief Summary

The main purposes of this study are to learn how effective the study drug combinations are in treating patients with metastatic pancreatic adenocarcinoma. The drug combinations are APX005M+Nivolumab+Gemcitabine+nab-Paclitaxel, or APX005M+Gemcitabine+nab-Paclitaxel.

Conditions

Metastatic Pancreatic Adenocarcinoma

Keywords

Nivolumab; APX005M; previously untreated metastatic pancreatic adenocarcinoma; Gemcitabine; nab-Paclitaxel

Outcome Measures

Primary Outcomes (2)

• Phase 1b Primary Safety Outcome

  Number and percentage of subjects with adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)

  Initiation of study drug (or informed consent for SAEs) through 100 days after the last dose of study drug or initiation of a new systemic anti-cancer therapy with a maximum exposure of 34.3 months.

• 1-year Overall Survival Rate

  The primary endpoint was the 1-year OS rate of each treatment arm, compared to the historical rate of 35% for gemcitabine and nab-Paclitaxel. OS was defined as the time from treatment initiation until death from any cause. Patients who were not reported as having died at the time of analysis were censored at the most recent contact date. OS and the 1-year OS rate were estimated by the Kaplan-Meier method for each treatment arm. The 1-year OS rate and corresponding one-sided, 95% CI were calculated to determine whether the lower bound of the CI excluded the assumed historical value of 35%. P values were calculated using a one-sided, one-sample z-test of the Kaplan-Meier estimate of the 1-year OS rate (and its standard error) against the historical rate of 35%. This study was not powered for statistical comparison between arms.

  1 year from initiation of study therapy

Secondary Outcomes (6)

• Objective Response Rate (ORR): DLT-Evaluable Population

  Initiation of study drug through radiographic progression or initiation of new anti-cancer therapy with a maximum exposure of 34.3 months.

• Duration of Response (DOR): DLT-Evaluable Population

  Initiation of study drug through radiographic progression or initiation of new anti-cancer therapy with a maximum exposure of 34.3 months.

• Disease Control Rate (DCR)

  Initiation of study drug through radiographic progression or initiation of new anti-cancer therapy with a maximum exposure of 24.2 months.

• Progression-free Survival (PFS)

  Initiation of study drug through radiographic progression or death with a maximum exposure of 24.2 months.

• Objective Response Rate (ORR): Efficacy Population

  Initiation of study drug through radiographic progression or initiation of new anti-cancer therapy with a maximum exposure of 24.2 months.

Study Arms (3)

Gem/NP/nivolumab

EXPERIMENTAL

Gemcitabine+Nab-Paclitaxel+nivolumab

Drug: Nivolumab; Drug: Nab-Paclitaxel; Drug: Gemcitabine

Gem/NP/APX005M

EXPERIMENTAL

Gemcitabine+Nab-Paclitaxel+APX005M

Drug: APX005M; Drug: Nab-Paclitaxel; Drug: Gemcitabine

Gem/NP/nivolumab/APX005M

EXPERIMENTAL

Gemcitabine+Nab-Paclitaxel+nivolumab+APX005M

Drug: APX005M; Drug: Nivolumab; Drug: Nab-Paclitaxel; Drug: Gemcitabine

Interventions

APX005M DRUG

Administer intravenously once every 28-day Cycle

Gem/NP/APX005M; Gem/NP/nivolumab/APX005M

Nivolumab DRUG

Administer intravenously twice every 28-day cycle

Also known as: Opdivo

Gem/NP/nivolumab; Gem/NP/nivolumab/APX005M

Nab-Paclitaxel DRUG

Administer intravenously on 3 times every 28-day cycle

Also known as: Abraxane

Gem/NP/APX005M; Gem/NP/nivolumab; Gem/NP/nivolumab/APX005M

Gemcitabine DRUG

Administer intravenously 3 times every 28-day cycle

Also known as: Gemzar

Gem/NP/APX005M; Gem/NP/nivolumab; Gem/NP/nivolumab/APX005M

Eligibility Criteria

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

You may qualify if:

• Subject has histologically or cytologically documented diagnosis of pancreatic adenocarcinoma with metastatic disease. Locally advanced subjects are not eligible.
• Subject must have measureable disease by RECIST 1.1.
• Subjects must be age 18 years or older.
• Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Subjects must have the following laboratory values at screening within 2 weeks of the first dose of investigational agents:
• Absolute neutrophil count (ANC) ≥1.5 x 109/L (in absence of growth factor support)
• Platelet count ≥150 x 109/L
• Hemoglobin ≥9 g/dL(without transfusion support)
• Serum creatinine ≤1.5 mg/dL, and creatinine clearance ≥ 50 ml/min as measured by Cockcroft and Gault formula
• Aspartate aminotransferase (AST) and ALT ≤2.5 x upper limit of normal (ULN)
• Total bilirubin ≤1.5 x ULN, except in subjects with documented Gilbert's Syndrome, who must have a total bilirubin ≤3 x ULN
• Women of childbearing potential (WOCBP) must have a negative pregnancy test (serum or urine) within the 7 days prior to study drug administration, and within the 3 days before the first study drug administration, or a negative pregnancy test within the 24 hours before the first study drug administration.
• WOCBP and male subjects who are sexually active with WOCBP must agree to use 2 highly effective methods of contraception (including a physical barrier) before the first dose of study drugs, during the study, and for 5 months for women and 7 months for men following the last dose of study drug.
• Subjects must have the ability to understand and willingness to sign a written informed consent document.

You may not qualify if:

• Subject must not have received any prior treatment, including chemotherapy, biological therapy, or targeted therapy for metastatic pancreatic adenocarcinoma, with the following exceptions and notes:
• Subjects who have received prior adjuvant therapy for pancreatic adenocarcinoma are eligible if neoadjuvant and adjuvant therapy (including chemotherapy and/or radiotherapy) was fully completed more than 4 months before the start of study treatment. In this case, prior Gem and/or NP is allowable
• Prior resection surgery is allowable.
• Patients initially diagnosed with locally advanced pancreatic cancer who have undergone chemotherapy then resection and were with no evidence of disease are eligible if metastatic relapse of disease has occurred and if the last dose of chemotherapy was more than 4 months before the data of study entry.
• Subjects must not have another active invasive malignancy, with the following exceptions and notes:
• History of a non-invasive malignancy, such as cervical cancer in situ, non-melanomatous carcinoma of the skin, in situ melanoma, or ductal carcinoma in situ of the breast, is allowed.
• History of malignancy that is in complete remission after treatment with curative intent is allowed.
• No current or history of a hematologic malignancy is allowed, including subjects who have undergone a bone marrow transplant.
• History of clinically significant sensitivity or allergy to monoclonal antibodies, their excipients, or intravenous gamma globulin
• Previous exposure to CD40, PD-1, PD-L1, CTLA-4 antibodies or any other immunomodulatory agent
• History of (non-infectious) pneumonitis that required corticosteroids or current pneumonitis, or history of interstitial lung disease
• Subjects must not have a known or suspected history of an autoimmune disorder, including but not limited to inflammatory bowel disease, celiac disease, Wegner syndrome, Hashimoto syndrome, systemic lupus erythematosus, scleroderma, sarcoidosis, or autoimmune hepatitis, within 3 years of the first dose of investigational agent, except for the following.
• a. Subjects with Type 1 diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders such as vitiligo, or alopecia not requiring systemic therapy, or conditions not expected to recur in the absence of an external trigger are eligible.
• Subjects must not have an uncontrolled intercurrent illness, including an ongoing or active infection, current pneumonitis, symptomatic congestive heart failure (New York Heart Association class III or IV), unstable angina, uncontrolled hypertension, cardiac arrhythmia, interstitial lung disease, active coagulopathy, or uncontrolled diabetes.
• Subjects must not have a history of myocardial infarction within 6 months or a history of arterial thromboembolic event within 3 months of the first dose of investigational agent.

Sponsors & Collaborators

• Parker Institute for Cancer Immunotherapy: lead
• Bristol-Myers Squibb: collaborator
• Apexigen America, Inc.: collaborator
• Cancer Research Institute, New York City: collaborator

Study Sites (7)

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Pennsylvania, Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (8)

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• Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012 Jun 28;366(26):2443-54. doi: 10.1056/NEJMoa1200690. Epub 2012 Jun 2.

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• Padron LJ, Maurer DM, O'Hara MH, O'Reilly EM, Wolff RA, Wainberg ZA, Ko AH, Fisher G, Rahma O, Lyman JP, Cabanski CR, Yu JX, Pfeiffer SM, Spasic M, Xu J, Gherardini PF, Karakunnel J, Mick R, Alanio C, Byrne KT, Hollmann TJ, Moore JS, Jones DD, Tognetti M, Chen RO, Yang X, Salvador L, Wherry EJ, Dugan U, O'Donnell-Tormey J, Butterfield LH, Hubbard-Lucey VM, Ibrahim R, Fairchild J, Bucktrout S, LaVallee TM, Vonderheide RH. Sotigalimab and/or nivolumab with chemotherapy in first-line metastatic pancreatic cancer: clinical and immunologic analyses from the randomized phase 2 PRINCE trial. Nat Med. 2022 Jun;28(6):1167-1177. doi: 10.1038/s41591-022-01829-9. Epub 2022 Jun 3.

  PMID: 35662283 DERIVED

• O'Hara MH, O'Reilly EM, Varadhachary G, Wolff RA, Wainberg ZA, Ko AH, Fisher G, Rahma O, Lyman JP, Cabanski CR, Mick R, Gherardini PF, Kitch LJ, Xu J, Samuel T, Karakunnel J, Fairchild J, Bucktrout S, LaVallee TM, Selinsky C, Till JE, Carpenter EL, Alanio C, Byrne KT, Chen RO, Trifan OC, Dugan U, Horak C, Hubbard-Lucey VM, Wherry EJ, Ibrahim R, Vonderheide RH. CD40 agonistic monoclonal antibody APX005M (sotigalimab) and chemotherapy, with or without nivolumab, for the treatment of metastatic pancreatic adenocarcinoma: an open-label, multicentre, phase 1b study. Lancet Oncol. 2021 Jan;22(1):118-131. doi: 10.1016/S1470-2045(20)30532-5.

  PMID: 33387490 DERIVED

MeSH Terms

Interventions

sotigalimab; Nivolumab; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Gemcitabine

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Ute Dugan
• Organization: Parker Institute for Cancer Immunotherapy

udugan@parkerici.org

203-379-6757

Study Officials

• Parker Institute for Cancer Immunotherapy

  Parker Institute for Cancer Immunotherapy

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: 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: June 9, 2017
• First Posted: July 11, 2017
• Study Start: July 21, 2017
• Primary Completion: February 11, 2021
• Study Completion: February 25, 2022
• Last Updated: December 23, 2022
• Results First Posted: August 11, 2022

Record last verified: 2022-12

Locations

US (7)