Health TrialsbyHealthPanel

TCR1188-ABC Cells in KRAS-mutated Cancers

ConditionsCholangiocarcinomaColorectal CancerNon-Small Cell Lung CancerPancreatic Adenocarcinoma
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Pennsylvania

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Patients ≥ 18 years of age

Histologically confirmed metastatic pancreatic adenocarcinoma or cholangiocarcinoma

Histologically confirmed metastatic colorectal cancer

Histologically confirmed metastatic non-small cell lung cancer

Disqualifiers

Active hepatitis B or hepatitis C infection

Patients with a severe acquired or inherited immunodeficiency, including HIV positive patients with a CD4 count ≤ 350 cells/μL. In order to qualify, HIV positive patients must also be on an established antiretroviral therapy regimen with a viral load of <400 copies/mL.

Any other active, uncontrolled infection.

Class III/IV cardiovascular disability according to the New York Heart Association Classification (see Appendix 5).

Trial design

Design model

Sequential

Treatments tested in this trial

  • TCR1188-ABC cells

    Biological/Vaccine

    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

  • 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)

  • Tocilizumab

    Drug

    Single administration of 8mg/kg on Day 2 (+3d)

Treatment groups

30 Participants
are divided into 4 treatment groups
Group A: Dose level -1Experimental treatment 3 interventions
Group B: Dose level 1Experimental treatment 3 interventions
Group C: Dose level 2Experimental treatment 3 interventions
Group D: Dose level 3Experimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

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

Time frame
Up to 15 years following TCR1188-ABC cell administration
2

Occurrence of dose-limiting toxicities (DLTs)

Type, frequency, severity, and attribution of dose limiting adverse events as defined by the protocol

Time frame
Up to 28 days following TCR1188-ABC cell administration
3

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.

Time frame
28 days post-TCR1188-ABC cell infusion

Secondary outcomes

1

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.

Time frame
3 months
2

Proportion of TCR1188-ABC cells that fail to meet the protocol-defined dose

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.

Time frame
3 months
3

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.

Time frame
Up to 12 months following TCR1188-ABC cells administration
4

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.

Time frame
Up to 15 years following TCR1188-ABC cell administration

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Pennsylvania

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
Apply now