Metastatic Pancreatic AdenocarcinomaPhase 1/2NCT03214250
Safety and Efficacy of APX005M With Gemcitabine and Nab-Paclitaxel With or Without Nivolumab in Patients With Previously Untreated Metastatic Pancreatic Adenocarcinoma
A Phase 1/2 study testing APX005M, Nivolumab and Nab-Paclitaxel in people with Metastatic Pancreatic Adenocarcinoma, run by Parker Institute for Cancer Immunotherapy at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Pancreatic Adenocarcinoma
- What is being tested?
- APX005M, Nivolumab and Nab-Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 129 participants
- Where
- 7 sitesUnited States
- Study dates
- 21 Jul 2017to 25 Feb 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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.
Who cannot join
- 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.
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- 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.
- 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.
- Subjects must not have a history of human immunodeficiency virus, hepatitis B, or hepatitis C, except for the following:
- subjects with anti-hepatitis B core antibody but with undetectable HBV DNA and negative for HBsAg
- subjects with resolved or treated HCV (i.e. HCV antibody positive but undetectable HCV RNA)
- Subjects must not have a history of primary immunodeficiency.
- Subjects must not receive concurrent or prior use of an immunosuppressive agent within 14 days of the first dose of investigational agent, with the following exceptions and notes:
- Systemic steroids at physiologic doses (equivalent to dose of oral prednisone 10 mg) are permitted. Steroids as anti-emetics for chemotherapy are not allowed.
- Intranasal, inhaled, topical, intra-articular, and ocular corticosteroids with minimal systemic absorption are permitted.
- Subjects with a condition with anticipated use of systemic steroids above the equivalent of 10 mg prednisone are excluded.
- Subjects must not have a history of clinically manifested central nervous system (CNS) metastases.
- Subjects with known or suspected leptomeningeal disease or cord compression are not eligible.
- Subjects must not have had major surgery as determined by the PI within 4 weeks before the first dose of investigational agent.
- Subjects must not have received another investigational agent within the shorter of 4 weeks or 5 half-lives before the first dose of investigational agent.
- Subjects must not have received a live attenuated vaccine within 28 days before the first dose of investigational agent, and subjects, if enrolled, should not receive live vaccines during the study or for 180 days after the last dose of investigational agent.
- Females who are pregnant or lactating or who intend to become pregnant during participation in the study are not eligible to participate.
- Subjects who are of reproductive potential who refuse to use effective methods of birth control during the course of participation of the study and within 5 month for women and 7 months for men of the last dose of investigational agent are ineligible to participate in the study.
- Subjects who have any clinically significant psychiatric, social, or medical condition that, in the opinion of the investigator, could increase the subject's risk, interfere with protocol adherence, or affect the subject's ability to give informed consent are ineligible to participate in the study.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
M.D. Anderson Cancer Center
Houston, Texas, 77030
University of California, Los Angeles
Los Angeles, California, 90095
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
University of Pennsylvania, Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
University of California, San Francisco
San Francisco, California, 94143
Stanford University
Stanford, California, 94305
About this study
Official title: 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
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
- Being tested
- APX005M, Nivolumab, Nab-Paclitaxel, Gemcitabine
- Keywords
- Nivolumab, APX005M, previously untreated metastatic pancreatic adenocarcinoma, Gemcitabine, nab-Paclitaxel
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APX005MDrug
Administer intravenously once every 28-day Cycle
NivolumabDrug
Also called Opdivo
Administer intravenously twice every 28-day cycle
Nab-PaclitaxelDrug
Also called Abraxane
Administer intravenously on 3 times every 28-day cycle
GemcitabineDrug
Also called Gemzar
Administer intravenously 3 times every 28-day cycle
| Study group | Role | What they receive |
|---|---|---|
| Gem/NP/nivolumab | Experimental | Gemcitabine+Nab-Paclitaxel+nivolumab Receives: Drug: Nivolumab; Drug: Nab-Paclitaxel; Drug: Gemcitabine |
| Gem/NP/APX005M | Experimental | Gemcitabine+Nab-Paclitaxel+APX005M Receives: Drug: APX005M; Drug: Nab-Paclitaxel; Drug: Gemcitabine |
| Gem/NP/nivolumab/APX005M | Experimental | Gemcitabine+Nab-Paclitaxel+nivolumab+APX005M Receives: Drug: APX005M; Drug: Nivolumab; Drug: Nab-Paclitaxel; Drug: Gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1b Primary Safety Outcome
Number and percentage of subjects with adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)
Measured: 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.
Measured: 1 year from initiation of study therapy
Secondary outcomes (6)
Objective Response Rate (ORR): DLT-Evaluable Population
Phase 1b DLT-Evaluable Population. Overall Response Rate is defined as the proportion of participants who had a best overall response of Complete Response (CR) or Partial Response (PR) as defined by RECIST v1.1. Overall Response (OR) = CR + PR.
Measured: 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
DOR was the time from the first tumor assessment demonstrating response until the date of radiographic disease progression. DOR and the CIs were estimated using the Kaplan-Meier method.
Measured: 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)
Phase 2 Secondary Efficacy Outcome. Disease Control Rate is defined as the proportion of participants who had a best overall response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) as defined by RECIST v1.1.
Measured: 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)
PFS is defined as the time from treatment initiation until radiographic disease progression or death (whichever occurred first). PFS and the CIs were estimated using the Kaplan-Meier method.
Measured: Initiation of study drug through radiographic progression or death with a maximum exposure of 24.2 months.
Objective Response Rate (ORR): Efficacy Population
Phase 2 Secondary Efficacy Outcome. Overall Response Rate is defined as the proportion of participants who had a best overall response of Complete Response (CR) or Partial Response (PR) as defined by RECIST v1.1. Overall Response (OR) = CR + PR.
Measured: 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
DOR was the time from the first tumor assessment demonstrating response until the date of radiographic disease progression. DOR and the CIs were estimated using the Kaplan-Meier method.
Measured: Initiation of study drug through radiographic progression or initiation of new anti-cancer therapy with a maximum exposure of 24.2 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2017
- Study start21 Jul 2017
- Primary completion11 Feb 2021
- Study completion25 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Metastatic Pancreatic AdenocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 129 participants (actual)
Sponsor and investigators
- Lead sponsor
- Parker Institute for Cancer Immunotherapy
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb, Apexigen America, Inc., Cancer Research Institute, New York City
- Responsible party
- Sponsor
- Investigators
- Parker Institute for Cancer Immunotherapy, Study director, Parker Institute for Cancer Immunotherapy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03214250
- Sponsor's protocol ID
- PICI0002
- Other IDs
- UPCC 11217
- Status last verified
- Dec 2022
- First submitted
- 9 Jun 2017
- Last updated
- 23 Dec 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014 Jun 1;74(11):2913-21. doi: 10.1158/0008-5472.CAN-14-0155.
PubMed 24840647Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013 Oct 31;369(18):1691-703. doi: 10.1056/NEJMoa1304369. Epub 2013 Oct 16.
PubMed 24131140Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012 Mar 22;12(4):252-64. doi: 10.1038/nrc3239.
PubMed 22437870Bauer C, Kuhnemuth B, Duewell P, Ormanns S, Gress T, Schnurr M. Prevailing over T cell exhaustion: New developments in the immunotherapy of pancreatic cancer. Cancer Lett. 2016 Oct 10;381(1):259-68. doi: 10.1016/j.canlet.2016.02.057. Epub 2016 Mar 8.
PubMed 26968250Khong A, Nelson DJ, Nowak AK, Lake RA, Robinson BW. The use of agonistic anti-CD40 therapy in treatments for cancer. Int Rev Immunol. 2012 Aug;31(4):246-66. doi: 10.3109/08830185.2012.698338.
PubMed 22804570Topalian 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.
PubMed 22658127Padron 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.
PubMed 35662283O'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.
PubMed 33387490
Study at a glance
From the registry record, last updated by the sponsor on 23 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03214250
- Acronym / sponsor ID
- PICI0002
- Conditions
- Metastatic Pancreatic Adenocarcinoma
- Keywords
- Nivolumab, APX005M, previously untreated metastatic pancreatic adenocarcinoma, Gemcitabine, nab-Paclitaxel
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 129 participants (actual)
- Lead sponsor
- Parker Institute for Cancer ImmunotherapyUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb, Apexigen America, Inc., Cancer Research Institute, New York City
- Study start
- 21 Jul 2017 (actual)
- Primary completion
- 11 Feb 2021 (actual)
- Study completion
- 25 Feb 2022 (actual)
- First posted
- 11 Jul 2017 (actual)
- Results
- Posted 11 Aug 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Gem/NP/nivolumab | Experimental | Drug: Nivolumab, Drug: Nab-Paclitaxel, Drug: GemcitabineGemcitabine+Nab-Paclitaxel+nivolumab |
| Gem/NP/APX005M | Experimental | Drug: APX005M, Drug: Nab-Paclitaxel, Drug: GemcitabineGemcitabine+Nab-Paclitaxel+APX005M |
| Gem/NP/nivolumab/APX005M | Experimental | Drug: APX005M, Drug: Nivolumab, Drug: Nab-Paclitaxel, Drug: GemcitabineGemcitabine+Nab-Paclitaxel+nivolumab+APX005M |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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:
Key exclusion criteria (31 listed)
- 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 must not have another active invasive malignancy, with the following exceptions and notes:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| APX005MAdminister intravenously once every 28-day Cycle | Drug | Gem/NP/APX005M, Gem/NP/nivolumab/APX005M |
| NivolumabAlso: OpdivoAdminister intravenously twice every 28-day cycle | Drug | Gem/NP/nivolumab, Gem/NP/nivolumab/APX005M |
| Nab-PaclitaxelAlso: AbraxaneAdminister intravenously on 3 times every 28-day cycle | Drug | Gem/NP/APX005M, Gem/NP/nivolumab, Gem/NP/nivolumab/APX005M |
| GemcitabineAlso: GemzarAdminister intravenously 3 times every 28-day cycle | Drug | Gem/NP/APX005M, Gem/NP/nivolumab, Gem/NP/nivolumab/APX005M |
Primary outcome
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.
6 secondary outcomes
Objective Response Rate (ORR): DLT-Evaluable Population
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: Initiation of study drug through radiographic progression or death with a maximum exposure of 24.2 months.
Objective Response Rate (ORR): Efficacy Population
Time frame: 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
Time frame: Initiation of study drug through radiographic progression or initiation of new anti-cancer therapy with a maximum exposure of 24.2 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Dec 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 24840647Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014 Jun 1;74(11):2913-21. doi: 10.1158/0008-5472.CAN-14-0155.
- Background: PubMed 24131140Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013 Oct 31;369(18):1691-703. doi: 10.1056/NEJMoa1304369. Epub 2013 Oct 16.
- Background: PubMed 22437870Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012 Mar 22;12(4):252-64. doi: 10.1038/nrc3239.
- Background: PubMed 26968250Bauer C, Kuhnemuth B, Duewell P, Ormanns S, Gress T, Schnurr M. Prevailing over T cell exhaustion: New developments in the immunotherapy of pancreatic cancer. Cancer Lett. 2016 Oct 10;381(1):259-68. doi: 10.1016/j.canlet.2016.02.057. Epub 2016 Mar 8.
- Background: PubMed 22804570Khong A, Nelson DJ, Nowak AK, Lake RA, Robinson BW. The use of agonistic anti-CD40 therapy in treatments for cancer. Int Rev Immunol. 2012 Aug;31(4):246-66. doi: 10.3109/08830185.2012.698338.
- Background: PubMed 22658127Topalian 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.
- Derived from this study: PubMed 35662283Padron 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.
- Derived from this study: PubMed 33387490O'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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Parker Institute for Cancer Immunotherapy study director
Parker Institute for Cancer Immunotherapy
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing APX005M, Nivolumab and Nab-Paclitaxel in people with Metastatic Pancreatic Adenocarcinoma, run by Parker Institute for Cancer Immunotherapy at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Aug 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03214250, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Dec 2022.