Pancreatic Cancer (Unresectable)
Conditions
Keywords
locally, advanced, pancreatic, cancer, unresectable, pancreatic cancer
Brief summary
This is a Phase 1/2 trial to evaluate the safety, tolerability, and efficacy of FG-3019 administered with gemcitabine and nab-paclitaxel in the treatment of locally advanced, unresectable pancreatic cancer.
Interventions
DRUGFG-3019
FG-3019 will be administered per dose and schedule specified in the arm group description.
DRUGGemcitabine
Gemcitabine will be administered per dose and schedule specified in the arm group description.
DRUGNab-paclitaxel
Nab-paclitaxel will be administered per dose and schedule specified in the arm group description.
Sponsors
Kyntra Bio
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Male, or non-pregnant and, non-lactating female * Histologically proven diagnosis of pancreatic ductal adenocarcinoma (PDAC) * Radiographic and pathologic staging consistent with pancreatic cancer, locally advanced, unresectable (per National Comprehensive Cancer Network® \[NCCN®\] criteria) * Laparoscopic confirmation that PDAC is locally advanced. Biliary stents are permitted. * Measurable disease as defined by RECIST 1.1 * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Adequate liver, bone marrow, and renal function * Agree to use contraception per protocol * Less than Grade 2 pre-existing peripheral neuropathy Key
Exclusion criteria
* Prior chemotherapy or radiation for pancreatic cancer * Solid tumor contact with superior mesenteric artery (SMA) \>180° * Previous (within the past 5 years) or concurrent malignancy diagnosis (expect non-melanoma skin cancer and in situ carcinomas) * Major surgery, within 4 weeks prior to Day 1 on study * History of allergy or hypersensitivity to human, humanized or chimeric monoclonal antibodies * Exposure to another investigational drug within 42 days of first dosing visit, or 5 half-lives of the study product (whichever is longer) * Uncontrolled intercurrent illness * Any medical condition that, in the opinion of the Investigator, may pose a safety risk to a participant in this trial, may confound the assessment of safety and efficacy, or may interfere with study participation. * Current abuse of alcohol or drugs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From first infusion of any study drug (Day 1) up to 28 days after last infusion of study drug or the day before surgery (up to Day 196) | An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. SAEs included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A TEAE was defined as a new or worsening AE that occurred in the window of first infusion of any study drug (Day 1) and within 28 days of the last infusion of study drug or the day before surgery, whichever occurred first. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'. |
| Number of Participants Who Had Surgical Complications Post-Resection | 30 days following discharge after surgery (up to Day 198) | Number of participants who had surgical complications (for example; surgical site infection, intra-abdominal abscess, or perioperative leak during surgery) has been reported |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants in Whom R0 Resection Was Achieved | After completion of 24 weeks of treatment with study drug | R0 resection was determined by pathological examination of the surgical specimen after resection. |
| Number of Participants With Complete Response (CR) or Partial Response (PR) Per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) | From randomization up to Week 52 | CR was defined as disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduced in short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Number of Participants in Whom R0 or R1 Resection Was Achieved | After completion of 24 weeks of treatment with study drug | R0 or R1 resection was determined by pathological examination of the surgical specimen after resection. |
| Median Progression-Free Survival | From randomization until objective tumor progression or death, assessed up to 4 years | Progression-free survival was defined as the time from randomization until objective tumor progression or death. Progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. |
| Median Overall Survival | From randomization until death from any cause, assessed up to 4 years | Overall survival was defined as the time from randomization until death from any cause. |
| Number of Participants Who Became Eligible for Surgery | After completion of 24 weeks of treatment with study drug | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm A: Gemcitabine Plus Nab-paclitaxel + Pamrevlumab (G/NP+P) Participants received gemcitabine at 1000 mg/m\^2 plus nab-paclitaxel at 125 mg/m\^2 by IV infusion on Days 1, 8, and 15 of each cycle. Participants received pamrevlumab at 35 mg/kg by IV infusion on Days 1 and 15 of each cycle. An additional dose of pamrevlumab was given on Day 8 of the first cycle. Participants received a total of up to six 28-day cycles of treatment. | 24 |
| Arm B: Gemcitabine Plus Nab-paclitaxel (G/NP) Participants received gemcitabine at 1000 mg/ m\^2 plus nab-paclitaxel at 125 mg/m\^2 by IV infusion on Days 1, 8, and 15 of each cycle. Participants received a total of up to six 28-day cycles of treatment. | 13 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 |
| Overall Study | Other than specified | 0 | 1 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Progressive Disease | 3 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Arm B: Gemcitabine Plus Nab-paclitaxel (G/NP) | Total | Arm A: Gemcitabine Plus Nab-paclitaxel + Pamrevlumab (G/NP+P) |
|---|---|---|---|
| Age, Continuous | 60.8 years STANDARD_DEVIATION 9.18 | 64.4 years STANDARD_DEVIATION 8.6 | 66.4 years STANDARD_DEVIATION 7.75 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 36 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 32 Participants | 22 Participants |
| Sex: Female, Male Female | 7 Participants | 23 Participants | 16 Participants |
| Sex: Female, Male Male | 6 Participants | 14 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 17 / 24 | 7 / 13 |
| other Total, other adverse events | 24 / 24 | 12 / 13 |
| serious Total, serious adverse events | 9 / 24 | 6 / 13 |
Outcome results
Primary
Number of Participants Who Had Surgical Complications Post-Resection
Number of participants who had surgical complications (for example; surgical site infection, intra-abdominal abscess, or perioperative leak during surgery) has been reported
Time frame: 30 days following discharge after surgery (up to Day 198)
Population: ITT population included all randomized participants who received any amount of study drugs including pamrevlumab, or gemcitabine, or nab-paclitaxel.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: Gemcitabine Plus Nab-paclitaxel + Pamrevlumab (G/NP+P) | Number of Participants Who Had Surgical Complications Post-Resection | 0 Participants |
| Arm B: Gemcitabine Plus Nab-paclitaxel (G/NP) | Number of Participants Who Had Surgical Complications Post-Resection | 0 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. SAEs included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A TEAE was defined as a new or worsening AE that occurred in the window of first infusion of any study drug (Day 1) and within 28 days of the last infusion of study drug or the day before surgery, whichever occurred first. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'.
Time frame: From first infusion of any study drug (Day 1) up to 28 days after last infusion of study drug or the day before surgery (up to Day 196)
Population: Safety population included all participants who had received any dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: Gemcitabine Plus Nab-paclitaxel + Pamrevlumab (G/NP+P) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 24 Participants |
| Arm A: Gemcitabine Plus Nab-paclitaxel + Pamrevlumab (G/NP+P) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 9 Participants |
| Arm B: Gemcitabine Plus Nab-paclitaxel (G/NP) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 12 Participants |
| Arm B: Gemcitabine Plus Nab-paclitaxel (G/NP) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 6 Participants |
Secondary
Median Overall Survival
Overall survival was defined as the time from randomization until death from any cause.
Time frame: From randomization until death from any cause, assessed up to 4 years
Population: ITT population included all randomized participants who received any amount of study drugs including pamrevlumab, or gemcitabine, or nab-paclitaxel.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Gemcitabine Plus Nab-paclitaxel + Pamrevlumab (G/NP+P) | Median Overall Survival | 19.38 months |
| Arm B: Gemcitabine Plus Nab-paclitaxel (G/NP) | Median Overall Survival | 23.47 months |
Secondary
Median Progression-Free Survival
Progression-free survival was defined as the time from randomization until objective tumor progression or death. Progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression.
Time frame: From randomization until objective tumor progression or death, assessed up to 4 years
Population: ITT population included all randomized participants who received any amount of study drugs including pamrevlumab, or gemcitabine, or nab-paclitaxel.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Gemcitabine Plus Nab-paclitaxel + Pamrevlumab (G/NP+P) | Median Progression-Free Survival | 14.11 months |
| Arm B: Gemcitabine Plus Nab-paclitaxel (G/NP) | Median Progression-Free Survival | 11.63 months |
Secondary
Number of Participants in Whom R0 or R1 Resection Was Achieved
R0 or R1 resection was determined by pathological examination of the surgical specimen after resection.
Time frame: After completion of 24 weeks of treatment with study drug
Population: ITT population included all randomized participants who received any amount of study drugs including pamrevlumab, or gemcitabine, or nab-paclitaxel.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: Gemcitabine Plus Nab-paclitaxel + Pamrevlumab (G/NP+P) | Number of Participants in Whom R0 or R1 Resection Was Achieved | 8 Participants |
| Arm B: Gemcitabine Plus Nab-paclitaxel (G/NP) | Number of Participants in Whom R0 or R1 Resection Was Achieved | 1 Participants |
Secondary
Number of Participants in Whom R0 Resection Was Achieved
R0 resection was determined by pathological examination of the surgical specimen after resection.
Time frame: After completion of 24 weeks of treatment with study drug
Population: ITT population included all randomized participants who received any amount of study drugs including pamrevlumab, or gemcitabine, or nab-paclitaxel.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: Gemcitabine Plus Nab-paclitaxel + Pamrevlumab (G/NP+P) | Number of Participants in Whom R0 Resection Was Achieved | 4 Participants |
| Arm B: Gemcitabine Plus Nab-paclitaxel (G/NP) | Number of Participants in Whom R0 Resection Was Achieved | 1 Participants |
Secondary
Number of Participants Who Became Eligible for Surgery
Time frame: After completion of 24 weeks of treatment with study drug
Population: ITT population included all randomized participants who received any amount of study drugs including pamrevlumab, or gemcitabine, or nab-paclitaxel.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: Gemcitabine Plus Nab-paclitaxel + Pamrevlumab (G/NP+P) | Number of Participants Who Became Eligible for Surgery | 17 Participants |
| Arm B: Gemcitabine Plus Nab-paclitaxel (G/NP) | Number of Participants Who Became Eligible for Surgery | 2 Participants |
Secondary
Number of Participants With Complete Response (CR) or Partial Response (PR) Per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
CR was defined as disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduced in short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From randomization up to Week 52
Population: ITT population included all randomized participants who received any amount of study drugs including pamrevlumab, or gemcitabine, or nab-paclitaxel.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: Gemcitabine Plus Nab-paclitaxel + Pamrevlumab (G/NP+P) | Number of Participants With Complete Response (CR) or Partial Response (PR) Per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) | 5 Participants |
| Arm B: Gemcitabine Plus Nab-paclitaxel (G/NP) | Number of Participants With Complete Response (CR) or Partial Response (PR) Per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) | 3 Participants |