Phase 1 Dose Escalation, Multi-tumor Study to Assess the Safety, Tolerability and Antitumor Activity of Genetically Engineered MAGE-A4ᶜ¹º³²T in HLA-A2+ Subjects With MAGE-A4 Positive Tumors

INTRODUCTION

  • Org Study ID: ADP-0044-001
  • Secondary ID: N/A
  • NTC ID: NCT03132922
  • Sponsor: Adaptimmune

BRIEF SUMMARY

This study will investigate the safety and tolerability of MAGE-A4ᶜ¹º³²T cell therapy in subjects who have the appropriate HLA-A2 tissue marker and whose urinary bladder, melanoma, head and neck, ovarian, non-small cell lung, esophageal, gastric, synovial sarcoma, or myxoid/round call liposarcoma (MRCLS) tumor has the MAGE-A4 protein expressed. This study will take a subject's T cells and give them a T cell receptor protein that recognizes and attacks the tumors. This study has a substudy component that will investigate the safety and tolerability of MAGE-A4c1032T cell therapy in combination with low dose radiation in up to 10 subjects.

  • Overall Status
    Recruiting
  • Start Date
    July 5, 2017
  • Phase
    Phase 1
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Number of subjects with adverse events (AE), including serious adverse events (SAEs).

Primary Outcome 1 - Timeframe: 3.5 years

Primary Outcome 2 - Measure: Determining dose limiting toxicities (DLT) and optimally tolerated dose range

Primary Outcome 2 - Timeframe: 3.5 years

Primary Outcome 3 - Measure: Evaluation of persistence of genetically modified T cells.

Primary Outcome 3 - Timeframe: 3.5 years

Primary Outcome 4 - Measure: Measurement of RCL in genetically modified T cells.

Primary Outcome 4 - Timeframe: 3.5 years

CONDITION

  • Urinary Bladder Cancer
  • Melanoma
  • Head and Neck Cancer
  • Ovarian Cancer
  • Non-Small Cell Lung Cancer
  • Esophageal Cancer
  • Gastric Cancer
  • Synovial Sarcoma
  • Myxoid Round Cell Liposarcoma
  • Gastroesophageal Junction

ELIGIBILITY

Inclusion Criteria:
Subject is ≥18 years of age at the time of signing the study informed consent.

- Subject has histologically confirmed diagnosis of any one of the indicated tumor types

- Subject is HLA-A*02 positive. (This determination will be made under screening protocol ADP-0000-001).

- Subject's tumor shows expression of the MAGE-A4 RNA or protein. (This determination will be made under screening protocol ADP-0000-001).

- Adequate organ function as indicated in the study protocol

- Subject has measurable disease according to RECIST v1.1 criteria prior to lymphodepletion

- Subject meets disease-specific requirements per protocol
7. Subject has anticipated life expectancy > 6 months prior to leukapheresis and >3 months prior to lymphodepletion.
Exclusion Criteria:
Subject does not express appropriate HLA-A genotype

- Subject is receiving excluded therapy/treatment per protocol

- Subject has symptomatic CNS metastases.

- Subject has any other active malignancy besides the tumor under study within 3 years prior to Screening. Subject has uncontrolled intercurrent illness.

- Subject has active infection with HIV, HBV, HCV or HTLV

- Subject is pregnant or breastfeeding.
Additional Exclusion Criteria for the Radiation Substudy:
Subject does not meet eligibility criteria for the main study (ADP-0044-001).

- Subject does not have at least one target lesion amenable to radiation.

- Certain radiation therapy within 6 months of clinical trial are an exclusion.

- Metastatic disease impinging on the spinal cord or threatening spinal cord compression.

Gender: All

Minimum Age: 18 Years

Maximum Age: 75 Years

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: David Hong, MD

Role: Principal Investigator

Affiliation: M.D. Anderson Cancer Center

Overall Contact

Name: David Hong, MD

Phone: 713-563-5844

Email: dshong@madanderson.org

LOCATION

Facility Status Contact
Facility: M.D. Anderson Cancer Center
Houston, Texas 77030
United States
Status: Recruiting Contact: N/A
Facility: Princess Margaret Cancer Centre
Toronto, Ontario M5G1X6
Canada
Status: Recruiting Contact: N/A