TCR1020-CD8 T Cells in KRAS-mutated Cancers

NCT06707896 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 18224
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Phase I, open-label dose finding study to assess the safety, manufacturing feasibility, and preliminary efficacy of TCR1020-CD8 T cells in patients with KRAS-mutated cancers. Initially, patients with KRAS G12V mutation positive metastatic pancreatic adenocarcinoma or colorectal cancer will be targeted for participation. Up to 4 total dose levels will be evaluated using a 3+3 dose escalation design.

Conditions

Metastatic Pancreatic Adenocarcinoma; Colorectal Cancer

Outcome Measures

Primary Outcomes (3)

• Number of Subjects with dose limiting toxicities (DLTs)

  28 days after TCR1020-CD8 T cells

• Determination of maximum tolerated does (MTD)

  28 days after TCR1020-CD8 T cells

• Incidence of Adverse Events as assessed by CTCAE v5.0

  Up to 15 years

Secondary Outcomes (5)

• Percentage of manufacturing products that meet release criteria

  Up to 3 years

• Overall Response Rate (ORR)

  Up to one year

• Duration of Response (DOR)

  Up to one year

• Progression Free Survival (PFS)

  Up to 15 years

• Overall Survival (OS)

  Up to 15 years

Study Arms (4)

Dose Level 1

EXPERIMENTAL

After lymphodepleting chemotheerapy subjects will recieve a dose of 3 x 10(8) TCR1020-CD8 T cells

Drug: TCR1020-CD8 T cells

Dose Level -1

EXPERIMENTAL

After lymphodepleting chemotheerapy subjects will recieve a dose 1 x 10(8) TCR1020-CD8 T cells

Drug: TCR1020-CD8 T cells

Dose Level 2

EXPERIMENTAL

After lymphodepleting chemotheerapy subjects will recieve a dose 1 x 10(9) TCR1020-CD8 T cells

Drug: TCR1020-CD8 T cells

Dose Level 3

EXPERIMENTAL

After lymphodepleting chemotheerapy subjects will recieve a dose 3 x 10(9) TCR1020-CD8 T cells

Drug: TCR1020-CD8 T cells

Interventions

TCR1020-CD8 T cells DRUG

TCR1020-CD8 T cells are autologous mKRAS-redirected CD8+ T cells engineered using a lentiviral vector to express a TCR with specificity for HLA-restricted mKRAS G12V epitopes restricted to the HLA-A\*11:01 molecule.

Dose Level -1; Dose Level 1; Dose Level 2; Dose Level 3

Eligibility Criteria

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

You may qualify if:

• Patients ≥ 18 years of age
• Patients with one of the following diagnoses:
• Histologically confirmed metastatic pancreatic adenocarcinoma
• Histologically confirmed metastatic colorectal cancer
• HLA-A\*11:01 positive
• KRAS G12V mutation positive disease as confirmed by a CLIA certified laboratory.
• Received prior treatment for their primary malignancy as follows:
• Pancreatic Cancer Patients: At least one prior line of standard of care therapy for advanced stage disease
• Colorectal Cancer Patients: At least two prior lines of standard of care therapy for advanced stage disease.
• Evidence of active 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:
• Serum creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 50 cc/min per the Cockcroft-Gault Equation; Patient must not be on dialysis.
• ALT/AST ≤ 5 x ULN (patients with liver metastases) or ALT/AST ≤ 2.5 x ULN (patients without liver metastases)
• Direct bilirubin ≤ 2 mg/dL, unless the subject has Gilbert's syndrome (if so, direct bilirubin must be ≤3.0 mg/dL)
• Left Ventricle Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO

You may not qualify if:

• Active hepatitis B or hepatitis C infection
• Any other active, uncontrolled infection.
• Class III/IV cardiovascular disability according to the New York Heart Association Classification (see Appendix 5 of the protocol for full details).
• Severe, active co-morbidity that in the opinion of the physician-investigator would preclude participation in the study.
• Active invasive cancer, other than the proposed cancer included in the study, within 2 years prior to eligibility confirmation by a physician-investigator. \[Note: non-invasive cancers treated with curative intent (e.g., non-melanoma skin cancer) may still be eligible\].
• Pregnant or nursing (lactating) patients. Participants of reproductive potential must agree to use acceptable birth control methods, as described in protocol Section 4.3.
• Patients requiring chronic treatment with systemic steroids or immunosuppressant medications. Low-dose physiologic replacement therapy with corticosteroids equivalent to prednisone 10 mg/day or lower, topical steroids and inhaled steroids are acceptable. For additional details regarding use of steroid and immunosuppressant medications, please see protocol Section 5.6.
• Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded.
• History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).

Sponsors & Collaborators

• University of Pennsylvania: lead
• Stand Up To Cancer: collaborator
• Lustgarten Foundation: collaborator

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 3+3 dose escalation design

Study Record Dates

• First Submitted: November 25, 2024
• First Posted: November 27, 2024
• Study Start: June 1, 2025
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2044
• Last Updated: June 25, 2025

Record last verified: 2025-06