Colorectal Cancer, Esophageal Adenocarcinoma, Gastric Adenocarcinoma, Gastroesophageal Adenocarcinoma
Conditions
Keywords
CAR T, Adenovirus, ABECMA, BCMA, gastrointestinal cancer, CAR-T
Brief summary
This is a Phase 1, multicenter, open-label study of DISP-10, a combination therapy consisting of DV-10 (adenovirus) and idecabtagene vicleucel (ide-cel, BCMA-directed chimeric antigen receptor \[CAR\] T), in adult participants with advanced gastrointestinal (GI) cancers. The study will consist of 2 parts: dose-escalation (Part 1) and dose-expansion (Part 2). Part 1 of the study will evaluate the safety and tolerability of increasing dose levels of DISP-10 to establish the recommended dose for expansion (RDE); Part 2 will evaluate the safety and efficacy of DISP-10 in participants treated at the RDE.
Interventions
BIOLOGICALDISP-10
Participants will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) to produce ide-cel. During ide-cel production, participants may receive bridging therapy for disease control per Investigator discretion. DV-10 administration will be followed by lymphodepleting chemotherapy (fludarabine and cyclophosphamide) and subsequent ide-cel administration.
Sponsors
Dispatch Biotherapeutics
Bristol-Myers Squibb
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
Key Inclusion Criteria: 1. Histologically confirmed advanced or metastatic esophageal, gastroesophageal junction, gastric adenocarcinoma, or colorectal adenocarcinoma 2. Measurable disease according to RECIST v1.1 and at least 1 additional site of disease amenable to biopsy 3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 4. Aged ≥18 years at time of signing informed consent 5. Adequate organ function Key
Exclusion criteria
1. Previous solid organ or hematopoietic cell transplant 2. Evidence of rapid disease progression, defined as radiographic or clinical progression within 3 months of the most recent prior line of therapy 3. Known history of hepatitis B or HIV infection 4. Previous or concurrent malignancy except if curatively treated more than 3 years prior to enrollment 5. Known active central nervous system (CNS) metastases 6. Clinically significant pleural or pericardial effusion or peritoneal carcinomatosis 7. Active treatment with antiviral agents 8. History of severe hypersensitivity to fludarabine or cyclophosphamide 9. Prior therapies/treatments with oncolytic viruses or T cell derived cellular therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment Emergent Adverse Events (TEAEs) | 90 days (2 years for related Serious Adverse Events) | Graded using National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) v6.0 |
| Incidence of Dose Limiting Toxicities (DLTs) [PART 1] | 28 days | Graded using National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) v6.0 |
| Identification of the Recommended Dose for Expansion (RDE) [PART 1] | Up to 2 years | To select the Recommended Dose for Expansion (RDE) for Part 2 |
| Overall response rate (ORR) [PART 2] | Up to 2 years | Confirmed complete response (CR) or partial response (PR), per RECIST v1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) [PART 1] | Up to 2 years | Confirmed CR or PR, per RECIST v1.1 |
| Disease control rate (DCR) | Up to 2 years | Proportion of participants with CR, PR, or stable disease per RECIST v1.1 |
| Duration of response (DOR) | Up to 2 years | Time from CR or PR to radiographic progression or death |
| Progression Free Survival (PFS) | Up to 2 years | Time from ide-cel administration to disease progression or death, whichever occurs first |
| Overall survival (OS) | Up to 15 years | Time from ide-cel administration to death |
| Time to response (TTR) | Up to 2 years | Time from ide-cel administration to the first documentation of objective tumor response |
| Cellular kinetics (CK) of ide-cel | Up to 2 years | Measurement of ide-cel CK in the blood |
| Pharmacokinetics of DV-10 - Cmax | Up to 2 years | Maximum concentration in blood |
| Pharmacokinetics of DV-10 - Tmax | Up to 2 years | Time to maximum concentration in blood |
| Pharmacokinetics of DV-10 - AUC | Up to 2 years | Area under the blood concentration curve |
Countries
United States
Contacts
CONTACTDispatch Clinical
Outcome results
None listed