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| ID | Type | Description | Link |
|---|---|---|---|
| 1UG3CA283652-01 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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This is a Phase I, open-label dose finding study to assess the safety, manufacturing feasibility, and preliminary efficacy of TCR1188-ABC cells in patients with KRAS-mutated cancers. Initially, patients with KRAS G12V mutation positive metastatic pancreatic adenocarcinoma, cholangiocarcinoma, colorectal cancer, or non-small cell lung cancer (NSCLC) will be targeted for participation. Up to 4 total dose levels will be evaluated using a 3+3 dose escalation design.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose level -1 | Experimental | 1.11 x 10^8 TCR1188-ABC cells |
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| Dose level 1 | Experimental | 3.33 x 10^8 TCR1188-ABC cells |
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| Dose level 2 | Experimental | 1 x 10^9 TCR1188-ABC cells |
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| Dose level 3 | Experimental | 3 x 10^9 TCR1188-ABC cells |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TCR1188-ABC cells | Biological | TCR1188 modified, base-edited autologous CD4+ and CD8+ T cells expressing TCR1188 and a scFv fragment specific to ILT4 (LILRB2) as a Single infusion on Day 0 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects with treatment related adverse events using NCI Common Terminology Criteria for Adverse Events (CTCAE) V6.0 | Type, frequency, severity, and attribution of adverse events | Up to 15 years following TCR1188-ABC cell administration |
| Occurrence of dose-limiting toxicities (DLTs) | Type, frequency, severity, and attribution of dose limiting adverse events as defined by the protocol | Up to 28 days following TCR1188-ABC cell administration |
| Identification of the maximum tolerated dose (MTD) | The highest dose at which 0 or 1 DLT occurs in 6 DLT-evaluable subjects will be declared the MTD. | 28 days post-TCR1188-ABC cell infusion |
| Measure | Description | Time Frame |
|---|---|---|
| Occurrence of product release failures | Calculated based on the proportion of subjects with TCR1188-ABC cell products that fail to meet the product release criteria, out of the number of eligible subjects in whom manufacturing was attempted, will be calculated. | 3 months |
| Proportion of TCR1188-ABC cells that fail to meet the protocol-defined dose |
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Inclusion Criteria:
Patients ≥ 18 years of age
Patients with one of the following diagnoses:
HLA-A*11:01 positive as confirmed by a CLIA certified laboratory.
KRAS G12V mutation positive disease as confirmed on tissue, blood, or plasma by next generation sequencing by a CLIA certified laboratory.
Received prior treatment for their primary malignancy as follows:
Evidence of radiographically detectable disease within 8 weeks of physician-investigator confirmation of eligibility.
Adequate organ function within 4 weeks of eligibility confirmation by a physician-investigator defined as:
Patients must have adequate hematologic reserve within 4 weeks of eligibility confirmation by a physician-investigator and must not be dependent on transfusions to maintain these hematologic parameters. Adequate hematologic reserve is defined as:
ECOG Performance Status that is either 0 or 1.
Signed, written informed consent
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Abramson Cancer Center Clinical Trials Service | Contact | 215-349-8245 | PMCancerResearch@pennmedicine.upenn.edu |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pennsylvania | Recruiting | Philadelphia | Pennsylvania | 19104 | United States |
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| ID | Term |
|---|---|
| D018281 | Cholangiocarcinoma |
| D015179 | Colorectal Neoplasms |
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| C024352 | fludarabine |
| C502936 | tocilizumab |
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| Fludarabine + Cyclophosphamide combination | Drug | Fludarabine: 30 mg/m2/day x 4 days (Day -7 to -4) Cyclophosphamide: 600mg/m2/day x 3 days (Day -7 to -5) |
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| Tocilizumab | Drug | Single administration of 8mg/kg on Day 2 (+3d) |
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Proportion of subjects with TCR1188-ABC cell products that fail to meet the assigned dose, out of the number of eligible subjects in whom manufacturing was attempted. |
| 3 months |
| Overall Response Rate (ORR) | Proportion of subjects with CR or PR as the best overall response as assessed by RECIST 1.1 from the first response assessment post-infusion until the end of the primary follow-up. | Up to 12 months following TCR1188-ABC cells administration |
| Duration of Response (DOR) | Duration of time from the date the response criteria of CR or PR is first met, to the date of confirmed disease progression, or the date of the last adequate disease assessment performed before the occurrence of another censoring event. | Up to 15 years following TCR1188-ABC cell administration |
| Progression-Free Survival (PFS) | Duration of time from the TCR1188-ABC cell infusion to the date of confirmed disease progression or death due to any cause, or the date of the last adequate disease assessment performed before the occurrence of another censoring event. | Up to 15 years following TCR1188-ABC cell administration |
| Overall Survival (OS) | Time from the first TCR1188-ABC cell infusion to death due to any cause; or censored at the date of last contact. | Up to 15 years after last TCR1188-ABC cells administration |
| D009369 | Neoplasms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |