Pancreatic Cancer Metastatic, Pancreatic Cancer Non-resectable
Conditions
Keywords
Antibody, Anti-PD-1, Human monoclonal immunoglobulin antibody, Immunotherapy, INCMGA00012 (anti-PD-1 antibody), Anti-PD-1 antibody (MGA012), Metastatic adenosquamous pancreatic cancer, Unresectable adenosquamous pancreatic cancer, Adenosquamous pancreatic cancer, Programmed cell death protein 1 (PD-1), Programmed death-ligand 1 (PD-L1)
Brief summary
Phase 2 study to evaluate the clinical activity of INCMGA00012 in patients with Unresectable or metastatic Adenosquamous Pancreatic or Ampullary Cancer.
Interventions
DRUGINCMGA00012 (PD-1 antibody)
INCMGA00012 (PD-1 antibody): 500 mg, 30 min IV infusion on Day 1 of each cycle (every 28 days)
Sponsors
Incyte Corporation
National Cancer Institute (NCI)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years. * Have histologically or cytologically - proven adenosquamous carcinoma of the pancreas or ampulla. * Has unresectable or metastatic measurable disease. * Has received (or been intolerant to or ineligible for) at least 1 prior line of cytotoxic chemotherapy and received no more than 2 prior systemic treatments. * Presence of at least one lesion with measurable disease. * Accept to have a tumor biopsy of an accessible lesion at baseline and on treatment. * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. * If HIV-positive, then all of the following criteria must also be met: cluster of differentiation (CD) 4+ count ≥ 350/μL, undetectable viral load, and receiving highly active antiretroviral therapy. * Life expectancy of greater than 3 months. * Patients must have adequate organ and marrow function defined by study-specified laboratory tests prior to initial study drug. * Woman of childbearing potential must have a negative pregnancy test and follow contraceptive guidelines as defined per protocol. * Men must use acceptable form of birth control while on study. * Ability to understand and willingness to sign a written informed consent document.
Exclusion criteria
* Known history or evidence of brain metastases. * Has had chemotherapy, radiation, or biological cancer therapy within 14 days prior to the first dose of study drug. * Has received an investigational agent or used an investigational device within 28 days of the first dose of study drug. * Expected to require any other form of systemic or localized antineoplastic therapy while on study. * Has had major surgery within 28 days of dosing of investigational agent, excluding minor procedures. * Has received a live vaccine within 28 days prior to the first dose of study drug. * Prior treatment with immunotherapy agents (including, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4, anti-OX40 and LAG-3 antibodies) * Have used any systemic steroids within 14 days of study treatment. * Hypersensitivity reaction to any monoclonal antibody. * Evidence of clinical or radiographic ascites. * Have clinically significant and/or malignant pleural effusion. * Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, metastatic cancer, or psychiatric illness/social situations that would limit compliance with study requirements. * History of autoimmune disease requiring systemic immunosuppression within the last 2 years. * Presence of any tissue or organ allograft, regardless of need for immunosuppression, including corneal allograft. Patients with a history of allogeneic hematopoeitic stem cell transplant will be excluded. * All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to a grade 1 or baseline before administration of study drug. * Infection with Hepatitis A, B or C. * Patient has a pulse oximetry of \<92% on room air. * Patient is on supplemental home oxygen. * Has an unhealed surgical wound or ulcer, or a bone fracture considered non-healing. * Patient has clinically significant heart disease. * Patient is, at the time of signing informed consent, a regular user (including recreational use) of any illicit drugs or other substance abuse. * Unwilling or unable to follow the study schedule for any reason. * Patient has history of non-infectious pneumonitis. * Serum albumin level less than 2.8 g/dL.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) at 4 Months Using RECIST 1.1 | 4 months | Disease control rate (DCR) is defined as the proportion of subjects with complete response, partial response and stable disease based on RECIST 1.1 criteria. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions. SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Subjects who discontinue due to toxicity prior to post-baseline tumor assessments will be evaluable and considered treatment failures. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Using RECIST 1.1. | 4 years | ORR is defined as the proportion subjects with partial response (PR) or complete response (CR) according to RECIST 1.1. Subjects who discontinue due to toxicity or clinical progression prior to post-baseline tumor assessments will be considered as non-responders |
| Progression-free Survival (PFS) | 34 months | Progression-free survival (PFS) is defined as the number of months from the first dose of retifanlimab to radiographic disease progression (PD or relapse from CR as assessed using RECIST 1.1 criteria), documented clinical progression as assessed by the treating provider, or death due to any cause. PFS will be censored at the date of the last scan for subjects without documentation of disease progression at the time of analysis. |
| Grade 3 and Higher Study Drug-related Toxicities. | 26 months | Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| INCMGA00012 (PD-1 Antibody) All participants received the interventional study drug; INCMGA00012.
INCMGA00012 (PD-1 antibody): 500 mg, 30 min IV infusion on Day 1 of each cycle (every 28 days) | 22 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | failed to maintained eligibility | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | INCMGA00012 (PD-1 Antibody) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 17 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG 0 | 6 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG 1 | 16 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Region of Enrollment United States | 22 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 17 / 25 |
| other Total, other adverse events | 21 / 25 |
| serious Total, serious adverse events | 9 / 25 |
Outcome results
Primary
Disease Control Rate (DCR) at 4 Months Using RECIST 1.1
Disease control rate (DCR) is defined as the proportion of subjects with complete response, partial response and stable disease based on RECIST 1.1 criteria. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions. SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Subjects who discontinue due to toxicity prior to post-baseline tumor assessments will be evaluable and considered treatment failures.
Time frame: 4 months
Population: One subject didnt have a follow up scan after receiving a dose of the study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| INCMGA00012 (PD-1 Antibody) | Disease Control Rate (DCR) at 4 Months Using RECIST 1.1 | 2 Participants |
Secondary
Grade 3 and Higher Study Drug-related Toxicities.
Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0.
Time frame: 26 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| INCMGA00012 (PD-1 Antibody) | Grade 3 and Higher Study Drug-related Toxicities. | Any grade 3 and higher related AE | 3 Participants |
| INCMGA00012 (PD-1 Antibody) | Grade 3 and Higher Study Drug-related Toxicities. | ALT increased | 2 Participants |
| INCMGA00012 (PD-1 Antibody) | Grade 3 and Higher Study Drug-related Toxicities. | AST increased | 1 Participants |
| INCMGA00012 (PD-1 Antibody) | Grade 3 and Higher Study Drug-related Toxicities. | Hypophosphatemia | 1 Participants |
Secondary
Objective Response Rate (ORR) Using RECIST 1.1.
ORR is defined as the proportion subjects with partial response (PR) or complete response (CR) according to RECIST 1.1. Subjects who discontinue due to toxicity or clinical progression prior to post-baseline tumor assessments will be considered as non-responders
Time frame: 4 years
Population: One subject didnt have a follow up scan after receiving a dose of the study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| INCMGA00012 (PD-1 Antibody) | Objective Response Rate (ORR) Using RECIST 1.1. | 0 Participants |
Secondary
Progression-free Survival (PFS)
Progression-free survival (PFS) is defined as the number of months from the first dose of retifanlimab to radiographic disease progression (PD or relapse from CR as assessed using RECIST 1.1 criteria), documented clinical progression as assessed by the treating provider, or death due to any cause. PFS will be censored at the date of the last scan for subjects without documentation of disease progression at the time of analysis.
Time frame: 34 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| INCMGA00012 (PD-1 Antibody) | Progression-free Survival (PFS) | 1.8 months |