Study of Anti-CEA CAR-T + Chemotherapy VS Chemotherapy Alone in Patients With CEA+Pancreatic Cancer & Liver Metastases

NCT04037241 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: STI-CEA-201
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Malignant Tumor of Pancreas Metastatic to Liver

Outcome Measures

Primary Outcomes (1)

• 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.

  6 - 12 months

Secondary Outcomes (14)

• Assess safety by monitoring adverse events

  6 - 12 months

• Assess efficacy by within-liver progression free survival (PFS)

  6 - 12 months

• Assess efficacy by progression free survival (PFS)

  6 - 12 months

• Assess efficacy by within-liver time to progression (TTP)

  6 - 12 months

• Assess efficacy by time to progression (TTP)

  6 - 12 months

Other Outcomes (3)

• Assess if serum cytokine levels correlate with response and/or toxicity to hepatic arterial infusions

  6 - 12 months

• Assess if neutrophil: lymphocyte ratio (NLR) correlate with response from hepatic arterial infusions

  6 - 12 months

• Assess the persistence of CAR-T cells in liver tumor biopsies over time.

  6 - 12 months

Study Arms (8)

2nd Line: Anti-CEA CAR-T Cells + gemcitabine/nab paclitaxel

EXPERIMENTAL

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

2nd Line: Anti-CEA CAR-T Cells Plus NLIR+FU/FA

EXPERIMENTAL

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

2nd Line: Gemcitabine /nab paclitaxel Alone

ACTIVE COMPARATOR

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

2nd Line: NLIR + FU/FA Alone

ACTIVE COMPARATOR

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

3rd Line: Anti-CEA CAR-T Cells Plus NLIR+FU/FA

EXPERIMENTAL

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

3rd Line: Anti-CEA CAR-T Cells Plus Capecitabine

EXPERIMENTAL

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

3rd Line: NLIR+FU/FA Alone

ACTIVE COMPARATOR

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

3rd Line: Capecitabine Alone

ACTIVE COMPARATOR

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

Interventions

Anti-CEA CAR-T cells BIOLOGICAL

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

2nd Line: Anti-CEA CAR-T Cells + gemcitabine/nab paclitaxel; 2nd Line: Anti-CEA CAR-T Cells Plus NLIR+FU/FA; 3rd Line: Anti-CEA CAR-T Cells Plus Capecitabine; 3rd Line: Anti-CEA CAR-T Cells Plus NLIR+FU/FA

gemcitabine/nab paclitaxel DRUG

systemic chemotherapy regimen

Also known as: Gemzar, Abraxane

2nd Line: Anti-CEA CAR-T Cells + gemcitabine/nab paclitaxel; 2nd Line: Gemcitabine /nab paclitaxel Alone

NLIR+FU/FA DRUG

systemic chemotherapy regimen

Also known as: Onivyde, Adrucil, Leucovorin

2nd Line: Anti-CEA CAR-T Cells Plus NLIR+FU/FA; 2nd Line: NLIR + FU/FA Alone; 3rd Line: Anti-CEA CAR-T Cells Plus NLIR+FU/FA; 3rd Line: NLIR+FU/FA Alone

Capecitabine DRUG

systemic chemotherapy regimen

Also known as: Xeloda

3rd Line: Anti-CEA CAR-T Cells Plus Capecitabine; 3rd Line: Capecitabine Alone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have documented CEA-expressing pancreatic adenocarcinoma with unresectable liver metastases. Documentation of CEA-expressing adenocarcinoma may be demonstrated by an elevated serum CEA level (≥ 10 ng/mL) or by the detection of CEA on the cell surface of adenocarcino3.
• Documentation of disease progression of pancreatic adenocarcinoma following the initiation of first-line treatment with FOLFIRINOX or gemcitabine-based therapy.ma cells by immunohistochemistry (IHC).
• The primary pancreatic tumor may be intact and limited lung metastases (≤ 3 lesions, none \> 1 cm in longest diameter) and lymphoid metastases (≤ 3 lesions, none \> 1 cm in longest diameter) are permitted.
• There must be at least one measurable metastatic liver lesion ( ≥ 10 mm in longest diameter).
• ECOG performance status of 0 or 1.
• Be willing and able to comply with the study schedule and all other protocol requirements.
• Females of childbearing potential must have 2 negative pregnancy tests prior to the start of study treatment, and must agree to pregnancy tests during the study; sexually active female and male patients must be willing to use an effective birth control to avoid pregnancy.

You may not qualify if:

• Received anti-cancer chemotherapy or investigational systemic anti-cancer treatments other than first line FOLFIRINOX or gemcitabine-based chemotherapy for advanced pancreatic adenocarcinoma.
• Received FOLFIRINOX or gemcitabine-based therapy within 14 days before receiving the first dose of study treatment.
• Have any unresolved toxicity \> Grade 1 from previous anticancer therapy, except for stable chronic toxicities (≤ Grade 2) that are not expected to resolve.
• Have a history of histologically confirmed metastases outside the liver, lungs, or lymph nodes.
• More than 50% replacement of one or both hepatic lobes with tumor.
• Tumor causing biliary obstruction not amenable to stenting.
• Received prior anti-CEA agents, CAR-T, CAR-T cell line, CAR-NK, CAR-pNK, or CAR-NK cell line therapies.
• Have any clinically significant low baseline lab results for hemoglobin, platelet counts, or neutrophil counts at screening.
• Has any untreated or ongoing intra-abdominal infection or bowel obstruction.
• Has any clinically significant elevated baseline lab results for serum creatinine, aspartate aminotransferase (AST), and total bilirubin (except for patients in whom hyperbilirubinemia is attributed to Gilbert's syndrome), and alkaline phosphatase at screening.
• Known HIV or acquired immunodeficiency syndrome-related illness, acute or history of chronic hepatitis B or C.
• Female patients who are pregnant or breastfeeding.
• Has active bacterial, viral or fungal infections.
• Has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from participating in the study.
• Has any condition, including the presence of laboratory abnormalities that places the patient at an unacceptable risk if the patient was to participate in the study.

Sponsors & Collaborators

• Sorrento Therapeutics, Inc.: lead

MeSH Terms

Interventions

Gemcitabine; Albumin-Bound Paclitaxel; irinotecan sucrosofate; Fluorouracil; Leucovorin; Capecitabine

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Uracil; Pyrimidinones; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Ying Yan, MD MS

  Sorrento Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2019
• First Posted: July 30, 2019
• Study Start: November 1, 2021
• Primary Completion: January 1, 2022
• Study Completion: January 1, 2022
• Last Updated: April 1, 2022

Record last verified: 2022-03