A Phase 2/3 interventional study of Anti-CEA CAR-T cells and gemcitabine/nab paclitaxel in Malignant Tumor of Pancreas Metastatic to Liver, sponsored by Sorrento Therapeutics, Inc.. Withdrawn. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-04-01.
Sponsored by Sorrento Therapeutics, Inc. · Phase 2/3, Interventional, and Treatment
This study is a randomized open-label phase 2b study of the efficacy and safety of regional infusion therapy with Anti-CEA CAR-T cells using the hepatic immunotherapy for metastases (HITM) method and the Trisalus pressure enabling drug delivery (PEDD) device alternating with systemic chemotherapy versus chemotherapy alone in patients with CEA-expressing pancreatic adenocarcinoma with liver metastases.
The study consists of 5 periods: Screening/Leukapheresis Period, Bridging Therapy Period, Randomization Period, Treatment Period, and Observation Period (which will be the long-term follow-up period to monitor for overall survival and long-term safety).
Patients in this trial with CEA-expressing pancreatic adenocarcinoma with liver metastases must have developed disease progression after first-line treatment with FOLFIRINOX (irinotecan, 5-fluorouracil, leucovorin, and oxaliplatin) or gemcitabine-based chemotherapy. Patients will be randomized to either the "anti-CEA CAR-T Cells + systemic chemotherapy treatment arms", or the "chemotherapy alone treatment arms."
If the patients achieve at least stable disease during the Bridging Therapy Period, they will be in the Second-Line Group of Treatment Arms. Patients who develop disease progression during the Bridging Period will be in the Third-Line Group of Treatment Arms.
Patients in the Second-Line or Third-Line treatment arms who are randomized to the treatment arms of "Anti-CEA CAR-T cells plus systemic chemotherapy" will receive hepatic infusions of Anti-CEA CAR-T cells in Cycles 1 and 3 (ie, each 42-day cycle is 3 weekly doses of Anti-CEA CAR-T cells administered as hepatic arterial infusions using a PEDD device with low dose systemic IL-2 support), alternating with the systemic chemotherapy regimen they received during the Bridging Therapy Period in Cycle 2 and Cycles >= 4. Systemic chemotherapy will be administered in 28-day cycles until the development of disease progression.
Patients in the Second-Line or Third-Line treatment arms who are randomized to the treatment arms "chemotherapy alone" arms will continue to receive the same systemic chemotherapy that they received during the Bridging Therapy Period. Systemic chemotherapy will be administered in 28-day or 21-day cycles (depending on the type of systemic chemotherapy regimen the patient will receive) until the development of disease progression.
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Exclusion Criteria:
Patients in the "anti-CEA CAR-T Cells plus gemcitabine/nab paclitaxel arm" will have achieved at least stable disease during the Bridging Therapy Period with gemcitabine/nab paclitaxel, and will receive the CAR-T cells in Cycles 1 and 3 and the gemcitabine/nab paclitaxel regimen they received during the Bridging Therapy Period in Cycle 2 and Cycles ≥ 4 of the Treatment Period. Treatment will continue until the development of disease progression.
Biological: Anti-CEA CAR-T cells · Drug: gemcitabine/nab paclitaxel
Patients in the "anti-CEA CAR-T Cells plus and nanolipsomal irinotecan (NLIR) + Fluorouracil/folinic acid (FU/FA)" will have achieved at least stable disease during the Bridging Therapy Period with NLIR + FU/FA, and will receive the CAR-T cells in Cycles 1 and 3 and the NLIR/FU/FA regimen they received during the Bridging Therapy Period in Cycle 2 and Cycles ≥ 4 of the Treatment Period. Treatment will continue until the development of disease progression.
Biological: Anti-CEA CAR-T cells · Drug: NLIR+FU/FA
Patients in the chemotherapy alone treatment arm who achieved at least stable disease during the Bridging Therapy Period while receiving gemcitabine plus nab paclitaxel will continue treatment with the chemotherapy regimen they received during the Treatment Period. This regimen will be administered in 28-day cycles until the development of disease progression.
Drug: gemcitabine/nab paclitaxel
Patients in the chemotherapy alone treatment arm who achieved at least stable disease during the Bridging Therapy Period while receiving nanoliposomal irinotecan (NLIR) + Fluorouracil/folinic acid (FU/FA) will continue treatment with the chemotherapy regimen they received during the Treatment Period. This regimen will be administered in 28-day cycles until the development of disease progression.
Drug: NLIR+FU/FA
Patients randomized to the anti-CEA CAR-T Cells plus chemotherapy treatment arm who developed disease progression during the Bridging Therapy Period will receive the CAR-T cells in Cycles 1 and 3. Nanoliposomal irinotecan plus fluorouracil/leucovorin chemotherapy will be administered in Cycle 2 and Cycles ≥ 4 of the Treatment Period to patients who progressed on nab paclitaxel plus gemcitabine during the Bridging Therapy Period. Treatment will continue until the development of disease progression.
Biological: Anti-CEA CAR-T cells · Drug: NLIR+FU/FA
Patients randomized to the anti-CEA CAR-T Cells plus chemotherapy treatment arm who developed disease progression during the Bridging Therapy Period will receive the CAR-T cells in Cycles 1 and 3. Capecitabine chemotherapy will be administered in Cycle 2 and Cycles ≥ 4 of the Treatment Period to patients who progressed on nanoliposomal irinotecan fluorouracil/leucovorin during the Bridging Therapy Period. Treatment will continue until the development of disease progression.
Biological: Anti-CEA CAR-T cells · Drug: Capecitabine
Patients randomized to the chemotherapy alone treatment arm who developed disease progression during the Bridging Therapy Period while receiving nab paclitaxel plus gemcitabine will be treated with nanoliposomal irinotecan plus fluorouracil/leucovorin during the Treatment Period.
Drug: NLIR+FU/FA
Patients that developed disease progression during the Bridging Therapy Period while receiving nanoliposomal irinotecan plus 5-FU/leucovorin will be treated with capecitabine during the Treatment Period.
Drug: Capecitabine
Doses will be delivered by hepatic arterial infusions using a pressure enabled drug delivery (PEDD) device
Also known as: SureFire Precision Infusion System, K171355, TriSalus PEDD
systemic chemotherapy regimen
Also known as: Gemzar, Abraxane
systemic chemotherapy regimen
Also known as: Onivyde, Adrucil, Leucovorin
systemic chemotherapy regimen
Also known as: Xeloda
Assess efficacy by overall survival
As a measure of activity, Overall Survival (OS) will be assessed. The events for the assessment of OS are death events. Time to event endpoints will be estimated using Kaplan-Meier methods. Point estimates and 95% confidence intervals will be provided where applicable.
Time frame: 6 - 12 months
Assess safety by monitoring adverse events
As a measure of safety, the types, frequencies, and severities of adverse events and their relationship to study drug will be summarized.
Time frame: 6 - 12 months
Assess efficacy by within-liver progression free survival (PFS)
As a measure of activity, within-liver PFS will be assessed. The events for the assessment of within-liver PFS will be measured from the date of randomization to the date of disease progression within the liver or death, whichever comes first. This time to event endpoint will be estimated using Kaplan-Meier methods. Point estimates and 95% confidence intervals will be provided where appropriate.
Time frame: 6 - 12 months
Assess efficacy by progression free survival (PFS)
As a measure of activity, PFS will be assessed. The events for the assessment of PFS will be measured from the date of randomization to the date of disease progression or death, whichever comes first. This time to event endpoint will be estimated using Kaplan-Meier methods. Point estimates and 95% confidence intervals will be provided where appropriate.
Time frame: 6 - 12 months
Assess efficacy by within-liver time to progression (TTP)
As a measure of activity, within-liver TTP will be assessed. The events for the assessment of within-liver TTP will be measured from the date of randomization to the date of disease progression within the liver. This time to event endpoint will be estimated using Kaplan-Meier methods. Point estimates and 95% confidence intervals will be provided where appropriate.
Time frame: 6 - 12 months
Assess efficacy by time to progression (TTP)
As a measure of activity, TTP will be assessed. The events for the assessment of TTP will be measured from the date of randomization to the date of disease progression. This time to event endpoint will be estimated using Kaplan-Meier methods. Point estimates and 95% confidence intervals will be provided where appropriate.
Time frame: 6 - 12 months
Assess efficacy by within-liver radiographic response rate using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
As a measure of activity, overall response rate within-liver will be assessed using radiographic scans using RECIST v 1.1 criteria. Response will be assessed for each patient over a 6- to 12-month timeframe during the Treatment and Observation Periods of the protocol.
Time frame: 6 - 12 months
Assess efficacy by overall whole-body radiographic response rate using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
As a measure of activity, overall response rate for overall whole-body will be assessed using radiographic scans using RECIST v 1.1 criteria. Response will be assessed for each patient over a 6- to 12-month timeframe during the Treatment and Observation Periods of the protocol.
Time frame: 6 - 12 months
Assess efficacy by duration of response within-liver in accordance with RECIST v 1.1 criteria
As a measure of activity, duration of response within-liver will be measured using radiologic scans and assessed according to RECIST v1.1 criteria. This will be assessed for each patient over a 6- to 12-month timeframe during the Treatment and Observation Periods of the protocol.
Time frame: 6 - 12 months
Assess efficacy by duration of response of overall whole-body in accordance with RECIST v 1.1 criteria
As a measure of activity, duration of response of overall whole-body will be measured using radiologic scans and assessed according to RECIST v1.1 criteria. This will be assessed for each patient over a 6- to 12-month timeframe during the Treatment and Observation Periods of the protocol.
Time frame: 6 - 12 months
Assess efficacy by serologic response rates by CEA levels
As a measure of activity, overall response rate will be assessed by serologic CEA levels. Response rate will be assessed for each patient over a 6- to 12-month timeframe during the Treatment and Observation Periods of the protocol.
Time frame: 6 - 12 months
Assess efficacy by serologic response rates by CA 19-9 levels
As a measure of activity, overall response rate will be assessed by serologic CA 19-9 levels. Response rate will be assessed for each patient over a 6- to 12-month timeframe during the Treatment and Observation Periods of the protocol.
Time frame: 6 - 12 months
Evaluation of Quality-of-Life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
As a measure of quality-of-life, the EORTC QLQ-C30 instrument will be administered at months 2, 4, 6 of the Treatment Period and at the end of study.
Time frame: 6 - 12 months
Evaluation of Quality-of-Life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Pancreatic Cancer Module (EORTC QLQ-PAN26)
As a measure of quality-of-life specific for patients with pancreatic cancer, the EORTC QLQ-PAN26 instrument will be administered at months 2, 4, 6 of the Treatment Period and at the end of study.
Time frame: 6 - 12 months
Evaluation of Quality-of-Life using the 5-level EQ-5D version (EQ-5D-5L) questionnaire
As a measure of quality-of-life, the EQ-5D-5L questionnaire will be administered at months 2, 4, 6 of the Treatment Period and at the end of study.
Time frame: 6 - 12 months
Assess if serum cytokine levels correlate with response and/or toxicity to hepatic arterial infusions
As an exploratory analysis, serum cytokine levels (pg/mL) will be measured over time by a standard laboratory test using Enzyme-linked immunosorbent assay (ELISA) to determine if increases in cytokines predict response and/or toxicity to liver arterial infusions.
Time frame: 6 - 12 months
Assess if neutrophil: lymphocyte ratio (NLR) correlate with response from hepatic arterial infusions
As an exploratory analysis, NLR will be calculated to determine if there is a correlation with response and/or toxicity.
Time frame: 6 - 12 months
Assess the persistence of CAR-T cells in liver tumor biopsies over time.
As an exploratory analysis, the engraftment of CAR-T cells in planned liver tumor biopsies will be analyzed to assess persistence of CAR-T cells during the Treatment and Observation Periods of the study.
Time frame: 6 - 12 months
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This study is withdrawn, as verified in Mar 2022. You cannot join it, but the record below documents what was studied.
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Sorrento Therapeutics, Inc.