Pancreatic Cancer, Adult
Conditions
Keywords
Pancreatic neoplasms, Pancreatic cancer, Pancreatic cancer, adult, Adenoma of the pancreas, Carcinoma of the pancreas
Brief summary
This was a Phase 1/2 multi-institution prospective open label study in which subjects with metastatic, locally advanced unresectable or recurrent pancreatic cancer who previously received treatment with chemotherapy with FOLFIRINOX or FOLFIRINOX-like regimen received the investigational agent NEO-102 (NPC-1C). The Phase 1 portion of this study evaluated the safety of NEO-102 in combination with Gemcitabine in a dose de-escalation design with a starting dose of 1.5 mg/kg/dose. If 2 of 6 patients experience DLT, the dose will be de-escalated to 1 mg/kg/dose to evaluate the safety of NEO-102 in combination with Gemcitabine. . In the Phase 2 portion patients were randomized into one of two arms: A: NPC-1C with gemcitabine and nab-paclitaxel or B: gemcitabine and nab-paclitaxel
Detailed description
During Part 1 of the study, the safe and tolerable dose of NEO-102 in combination with Gemcitabine will be determined using a dose de-escalation design. The starting dose of NEO-102 is 1.5 mg/kg/dose (Dose level 1). If 2 of 6 patients experience a DLT at the starting dose, the dose of NEO-102 will be de-escalated to 1 mg/kg/dose, and up to 6 patients will be treated at this Dose Level -1. Upon completion of the phase I study up to 90 patients be randomized to one of two arms: A: Patients will receive NPC-1C(NEO-102) infusion at the safe dose, and nab-paclitaxel (125 mg/m2 as a 30 minute infusion, maximum infusion time not to exceed 40 minutes) followed by gemcitabine (1000 mg/m2 as a 30 minute infusion) for 3 consecutive weeks (on Day 1, 7 and 15 ) followed by a week of rest (for a 28 day cycle). OR B: Patients will receive on Day 1, 7 and 15 nab-paclitaxel (125 mg/m2 as a 30 minute infusion, maximum infusion time not to exceed 40 minutes) followed by gemcitabine (1000 mg/m2 as a 30 minute infusion) for 3 consecutive weeks (on Day 1, 7 and 15). NPC-1C(NEO-102) infusion at a dose of 1.5mg/kg IV 30 minutes following the completion of the gemcitabine on days 1 and 15 of the 28 day cycle.
Interventions
DRUGGemcitabine
Gemcitabine IV at a dose of 1000mg/m2 on days 1, 8, and 15 of a 4 week cycle.
DRUGnab-paclitaxel
Nab-paclitaxel will be administered at a dose of 125 mg/m2 as a 30 minute infusion (maximum infusion time not to exceed 40 minutes) on Days 1, 7 and 15 for a 28 day cycle
DRUGNPC-1C
NPC-1C(NEO-102) infusion at a dose of 1.5mg/kg IV on days 1 and 15 of a 28 day cycle. This will be administered 30 minutes after completion of the gemcitabine infusion.
Sponsors
Precision Biologics, Inc
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Initial Phase 1 dose de-escalation design to determine the safe dose of NEO-102 in combination with gemcitabine. Then a Phase 2 randomized design to evaluate the safety and efficacy of gemcitabine and abraxane with or without NEO-102.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with recurrent, locally advanced unresectable or metastatic adenocarcinoma of the pancreas who have progressed after primary therapy with FOLFIRINOX or FOLFIRINOX-like regimen or were intolerant of it. * IHC greater than or equal to 20 percent of tumor on tissue sections must stain with NPC-1C. * 18 years of age or older. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Have an anticipated life expectancy of greater than 8 weeks. * Have recovered from any acute toxicity related to prior therapy. * If female, is post-menopausal, surgically sterilized or willing to use an effective method of contraception for the duration of the study and for 3 months after the end of treatment. If male, has agreed to use barrier method for contraception for the duration of the study and for 3 months after the end of treatment. * Must be willing to sign a written informed consent. * Laboratory tests must meet minimum safety requirements 1. Hemoglobin greater than or equal to 8.5 g/dL (may be receiving supportive therapy) 2. ANC greater than or equal to 1,500 K/uL 3. Platelets greater than or equal to 100 K/uL 4. Total bilirubin less than or equal to 2 mg/dL 5. ALT/AST less than or equal to 3 times ULN or less than or equal to 5 times ULN in the setting of liver metastases. 6. Creatinine less than or equal to 1.5 mg/dL or creatinine clearance greater than 40 mL/min/1.73 m2 for patients with creatinine levels above institutional normal, as calculated by the Cockcroft Gault formula. * Men and women of all races and ethnic groups are eligible for this trial.
Exclusion criteria
* Have received a second line chemotherapy after progressing on or not tolerating treatment with FOLFIRINOX as a first line. Prior adjuvant/neoadjuvant gemcitabine or gemcitabine-based radiation will not be counted as first line therapy. * Have known brain metastases. * Have had any major surgery within four weeks of enrollment. * Have greater than grade 2 ascites at time of enrollment. * Have received Gemcitabine for palliative treatment or progressed while receiving it or is within 3 months of completion in the adjuvant setting. * Have uncontrolled concomitant illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia. * Have serious medical or psychiatric illness that could, in the Investigator's opinion, potentially interfere with the completion of treatment according to this protocol. * Must not have other invasive malignancies within the past 3 years (with the exception of non-melanoma skin cancers or non-invasive bladder cancer). * Is pregnant or breast-feeding, since the effects of NPC-1C on the developing human fetus and nursing infants are unknown and potentially harmful, women of child-bearing potential must agree to use adequate contraception (hormonal or double barrier method of birth control or complete abstinence) prior to study entry, for the duration of study participation, and for three months after the last dose of investigational agent. * Have had any chemotherapy or systemic corticosteroids within 2 weeks of study entry. * Have acquired, hereditary or congenital immunodeficiencies including cellular immunodeficiencies, hypogammaglobulinemia and dysgammaglobulinemia. * Have a prior history of a documented hemolytic event. * Have a history of hypersensitivity to human or mouse antibody products. * Have a known history of HIV are excluded due to the possibility that Gemcitabine or NPC-1C(NEO-102) may worsen their condition and the likelihood that the underlying condition may obscure the attribution of adverse events with respect to Gemcitabine or NPC-1C(NEO-102).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability | 28 days | To determine the safety and tolerability of NPC-1C monoclonal antibody therapy in combination with Gemcitabine in subjects with metastatic, locally advanced unresectable or recurrent pancreatic cancer who failed or did not tolerate first line chemotherapy of FOLFIRINOX and whose tumors bind NPC-1C. |
| Overall Survival | From 1st dose of study therapy until death in participants in Phase 2. | To determine whether (only in participants in the Phase 2 portion (Arm A and Arm B) NPC-1C (NEO-102) in combination with Gemcitabine and nab-Paclitaxel will increase the overall survival (OS) compared to Gemcitabine and nab-Paclitaxel alone in patients with metastatic, locally advanced unresectable or recurrent pancreatic cancer previously treated with FOLFIRINOX and whose tumors bind NPC-1C by at least 20% on IHC. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | Time from the 1st dose of study drug until progression in patients in Arm A | To determine the progression free survival (PFS) and response rate (RR) of patients with metastatic or locally advanced unresectable or recurrent pancreatic cancer who progressed following or did not tolerate chemotherapy of FOLFIRINOX or FOLFIRINOX-like regimen when receiving the combination of NPC-1C(NEO-102) monoclonal antibody, Gemcitabine and nab-Paclitaxel (Arm A). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phase 1 Dose Finding: Dose Level 1 Patients on arm B will receive NPC-1C(NEO-102) infusion at a dose of 1.5mg/kg IV on days 1 and 15 of a 4-week cycle. This will be administered 30minutes after completion of the gemcitabine 1000 mg/m2 as a 30 minute infusion on days 1, 8, and 15 of a 4 week cycle. | 3 |
| Phase 1 Dose Finding: Dose Level -1 Patients on arm B will receive NPC-1C(NEO-102) infusion at a dose of 1.0 mg/kg IV on days 1 and 15 of a 4-week cycle. This will be administered 30minutes after completion of the gemcitabine 1000 mg/m2 as a 30 minute infusion on days 1, 8, and 15 of a 4 week cycle. | 0 |
| Arm A: Abraxane, Gemcitabine, NPC-1C Nab-paclitaxel will be administered at a dose of 125 mg/m2 as a 30 minute infusion (maximum infusion time not to exceed 40 minutes) followed by 1000 mg/m2 gemcitabine as a 30 minute infusion for 3 consecutive weeks followed by a week of rest.
Patients on arm B will receive NPC-1C(NEO-102) infusion at a dose of 1.5mg/kg IV on days 1 and 15 of a 4-week cycle. This will be administered 30minutes after completion of the gemcitabine infusion.
Gemcitabine: Gemcitabine IV at a dose of 1000mg/m2 on days 1, 8, and 15 of a 4 week cycle.
nab-paclitaxel: Nab-paclitaxel will be administered at a dose of 125 mg/m2 as a 30 minute infusion (maximum infusion time not to exceed 40 minutes) on Days 1, 7 and 15 for a 28 day cycle
NPC-1C: NPC-1C(NEO-102) infusion at a dose of 1.5mg/kg IV on days 1 and 15 of a 28 day cycle. This will be administered 30 minutes after completion of the gemcitabine infusion. | 38 |
| Arm B: Abraxane, Gemcitabine Nab-paclitaxel will be administered at a dose of 125 mg/m2 as a 30 minute infusion (maximum infusion time not to exceed 40 minutes) followed by 1000 mg/m2 gemcitabine as a 30 minute infusion for 3 consecutive weeks followed by a week of rest.
Gemcitabine: Gemcitabine IV at a dose of 1000mg/m2 on days 1, 8, and 15 of a 4 week cycle.
nab-paclitaxel: Nab-paclitaxel will be administered at a dose of 125 mg/m2 as a 30 minute infusion (maximum infusion time not to exceed 40 minutes) on Days 1, 7 and 15 for a 28 day cycle | 40 |
| Total | 81 |
Baseline characteristics
| Characteristic | Phase 1 Dose Finding: Dose Level 1 | Phase 1 Dose Finding: Dose Level -1 | Arm A: Abraxane, Gemcitabine, NPC-1C | Arm B: Abraxane, Gemcitabine | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 12 Participants | 16 Participants | 29 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 0 Participants | 26 Participants | 24 Participants | 52 Participants |
| Age, Continuous | 53 years | — | 62 years | 62.5 years | 62 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | — | 3 Participants | 4 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | — | 33 Participants | 34 Participants | 69 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | — | 2 Participants | 2 Participants | 4 Participants |
| NPC-1C IHC staining | 3 participants positive | — | 38 participants positive | 40 participants positive | 81 participants positive |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | — | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | — | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | — | 4 Participants | 5 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | — | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | — | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | — | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) White | 1 Participants | — | 32 Participants | 34 Participants | 67 Participants |
| Region of Enrollment United States | 3 participants | — | 38 participants | 40 participants | 81 participants |
| Sex: Female, Male Female | 3 Participants | — | 19 Participants | 29 Participants | 51 Participants |
| Sex: Female, Male Male | 0 Participants | — | 19 Participants | 11 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 38 / 38 | 40 / 40 | 3 / 3 | 0 / 0 |
| other Total, other adverse events | 32 / 38 | 33 / 40 | 0 / 3 | 0 / 0 |
| serious Total, serious adverse events | 18 / 38 | 12 / 40 | 0 / 3 | 0 / 0 |
Outcome results
Primary
Overall Survival
To determine whether (only in participants in the Phase 2 portion (Arm A and Arm B) NPC-1C (NEO-102) in combination with Gemcitabine and nab-Paclitaxel will increase the overall survival (OS) compared to Gemcitabine and nab-Paclitaxel alone in patients with metastatic, locally advanced unresectable or recurrent pancreatic cancer previously treated with FOLFIRINOX and whose tumors bind NPC-1C by at least 20% on IHC.
Time frame: From 1st dose of study therapy until death in participants in Phase 2.
Population: 78 participants who received study therapy in the Phase 2 portion of the study. Patients in the Phase 1 portion of the study were not included in the Analysis of outcome measure #2 because they only received NPC-1C and Gemcitabine.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1-Dose Finding Dose Level 1 | Overall Survival | 6.6 Number of months survival |
| Phase 1 Dose Finding: Dose Level -1 | Overall Survival | 5 Number of months survival |
Primary
Safety and Tolerability
To determine the safety and tolerability of NPC-1C monoclonal antibody therapy in combination with Gemcitabine in subjects with metastatic, locally advanced unresectable or recurrent pancreatic cancer who failed or did not tolerate first line chemotherapy of FOLFIRINOX and whose tumors bind NPC-1C.
Time frame: 28 days
Population: Dose level -1 did not enroll any patients because dose level 1 was found to be safe when NEO-102 was given in combination with Gemcitabine. Hence there was no need to dose de-escalate.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1-Dose Finding Dose Level 1 | Safety and Tolerability | 0 Participants |
| Arm A: Abraxane, Gemcitabine, NPC-1C | Safety and Tolerability | 3 Participants |
| Arm B: Abraxane, Gemcitabine | Safety and Tolerability | 7 Participants |
Secondary
Progression Free Survival
To determine the progression free survival (PFS) and response rate (RR) of patients with metastatic or locally advanced unresectable or recurrent pancreatic cancer who progressed following or did not tolerate chemotherapy of FOLFIRINOX or FOLFIRINOX-like regimen when receiving the combination of NPC-1C(NEO-102) monoclonal antibody, Gemcitabine and nab-Paclitaxel (Arm A).
Time frame: Time from the 1st dose of study drug until progression in patients in Arm A
Population: 78 participants who received study therapy in the Phase 2 portion of the study. Patients in the Phase 1 portion of the study were not included in the Analysis of outcome measure #3 because they only received NPC-1C and Gemcitabine.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1-Dose Finding Dose Level 1 | Progression Free Survival | 3.5 Median number of months without PD |
| Phase 1 Dose Finding: Dose Level -1 | Progression Free Survival | 2.7 Median number of months without PD |