Open-label, Multicenter, Phase 1b/2 Clinical Study to Evaluate the Safety and Efficacy of CD40 Agonistic Monoclonal Antibody (APX005M) Administered Together With Gemcitabine and Nab-Paclitaxel With or Without PD-1 Blocking Antibody (Nivolumab) in Patients With Previously Untreated Metastatic Pancreatic Adenocarcinoma
Overview
- Phase
- Phase 1
- Intervention
- Nivolumab
- Conditions
- Metastatic Pancreatic Adenocarcinoma
- Sponsor
- Parker Institute for Cancer Immunotherapy
- Enrollment
- 129
- Locations
- 7
- Primary Endpoint
- Phase 1b Primary Safety Outcome
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
- •Subjects must be age 18 years or older.
- •Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •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)
Exclusion Criteria
- •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
Arms & Interventions
Gem/NP/nivolumab
Gemcitabine+Nab-Paclitaxel+nivolumab
Intervention: Nivolumab
Gem/NP/nivolumab
Gemcitabine+Nab-Paclitaxel+nivolumab
Intervention: Nab-Paclitaxel
Gem/NP/nivolumab
Gemcitabine+Nab-Paclitaxel+nivolumab
Intervention: Gemcitabine
Gem/NP/APX005M
Gemcitabine+Nab-Paclitaxel+APX005M
Intervention: APX005M
Gem/NP/APX005M
Gemcitabine+Nab-Paclitaxel+APX005M
Intervention: Nab-Paclitaxel
Gem/NP/APX005M
Gemcitabine+Nab-Paclitaxel+APX005M
Intervention: Gemcitabine
Gem/NP/nivolumab/APX005M
Gemcitabine+Nab-Paclitaxel+nivolumab+APX005M
Intervention: APX005M
Gem/NP/nivolumab/APX005M
Gemcitabine+Nab-Paclitaxel+nivolumab+APX005M
Intervention: Nivolumab
Gem/NP/nivolumab/APX005M
Gemcitabine+Nab-Paclitaxel+nivolumab+APX005M
Intervention: Nab-Paclitaxel
Gem/NP/nivolumab/APX005M
Gemcitabine+Nab-Paclitaxel+nivolumab+APX005M
Intervention: Gemcitabine
Outcomes
Primary Outcomes
Phase 1b Primary Safety Outcome
Time Frame: 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.
Number and percentage of subjects with adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)
1-year Overall Survival Rate
Time Frame: 1 year from initiation of study therapy
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.
Secondary Outcomes
- 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.)
- Duration of Response (DOR): Efficacy Population(Initiation of study drug through radiographic progression or initiation of new anti-cancer therapy with a maximum exposure of 24.2 months.)