A Study of NT-175 in Adult Subjects With Unresectable, Advanced, and/or Metastatic Solid Tumors That Are Positive for HLA-A*02:01 and the TP53 R175H Mutation

ConditionsNon-small Cell Lung Cancer Head and Neck Squamous Cell Carcinoma Colorectal Carcinoma Pancreatic Adenocarcinoma Breast Cancer Other Solid Tumors Ovarian Cancer

Trial statusRecruiting

Trial phasePhase 1

Trial typeInterventional

Biological sexAll

Age18+

SponsorAstraZeneca

About this trial

Phase I Study of NT-175, an autologous T cell therapy product genetically engineered to express an HLA-A\*02:01-restricted T cell receptor (TCR), targeting TP53 R175H mutant solid tumors.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Subjects must be at least 18 years of age, at the time of signing the informed consent.

Subjects must be capable of giving signed informed consent.

NSCLC

Colorectal adenocarcinoma

Disqualifiers

Any another primary malignancy within the 3 years prior to enrollment (except for non-melanoma skin cancer, carcinoma in situ (eg, cervix, bladder, breast) or low-grade prostate cancer

Known, active primary central nervous system (CNS) malignancy

History of prior adoptive cell and gene therapy, allogeneic stem cell transplant or solid organ transplantation.

History of stroke or transient ischemic attack within the 12 months prior to enrollment.

Trial design

Design model

Single group

Treatments tested in this trial

Autologous, engineered T Cells targeting TP53 R175H
Biological/Vaccine
* Pre-conditioning by non-myeloablative chemotherapy with fludarabine and cyclophosphamide * Single infusion TCR T cells * Post-infusion recombinant interleukin-2 (rIL-2)

Treatment groups

45 Participants

are divided into 3 treatment groups

Group A: Dose Escalation and ExpansionExperimental treatment 1 intervention

Group B: Part 1: Disease Histology EvaluationExperimental treatment 1 intervention

Group C: Part 2: Disease Cohort ExpansionExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

Part 1: Safety of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors

Incidence of dose-limiting toxicities (DLTs) after the infusion of NT-175

Time frame

28 days after infusion

Part 1: Safety of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors

Incidence of adverse events and serious adverse events

Time frame

Up to 24 months post-infusion

Part 2: Further Evaluate the safety of NT-175 at the RP2D in subjects with unresectable, advanced, and/or metastatic solid tumors

Treatment-emergent adverse events, and serios adverse events

Time frame