MAGE A10ᶜ⁷⁹⁶T for Advanced NSCLC

Sponsor

Adaptimmune (Industry)

Overall Status

Completed

CT.gov ID

NCT02592577

Collaborator

(none)

Enrollment

Locations

Arm

64.5

Actual Duration (Months)

1.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This first time in human study is intended for men and women at least 18 years of age who have advanced lung cancer which has grown or returned after being treated. In particular, it is a study for subjects who have a blood test positive for HLA-A02:01 and/or HLA-A02:06 and a tumor test positive for MAGE A10 protein expression (protein or gene). This trial is a dose escalation trial that will evaluate 3 doses of transduced cells administered after a lymphodepleting chemotherapy regimen using a 3+3 dose escalation design .The study will take the subject's T cells, which are a natural type of immune cell in the blood, and send them to a laboratory to be modified. The changed T cells used in this study will be the subject's own T cells that have been genetically changed with the aim of attacking and destroying cancer cells.

When the MAGE A10ᶜ⁷⁹⁶T cells are available, subjects will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine, followed by the T cell infusion. The purpose of this study is to test the safety of genetically changed T cells and find out what effects, if any, they have in subjects with lung cancer. The study will evaluate three different cell dose levels in order to find out the target cell dose. Once the target cell dose is determined, additional subjects will be enrolled to further test the safety and effects at this cell dose.

Subjects will be seen frequently by the Study Physician right after receiving their T cells back and up to first 6 months. After that, subjects will be seen every three months. Subjects will be seen every 6 months by their Study Physician for the first 5 years after the T cell infusion. If the T cells are found in the blood at five years, then the subjects will continue to be seen once a year until the T cells are no longer found in the blood for a maximum of 15 years. If the T cells are no longer found in the blood at 5 years, then the subject will be contacted by the Study Physician for the next 10 years. Subjects who have a confirmed response or clinical benefit ≥4 weeks after the first T-cell infusion and whose tumor continues to express the appropriate antigen target may be eligible for a second infusion. All subjects, completing or withdrawing from the Interventional Phase of the study, will enter a 15-year long-term follow-up phase for observation of delayed adverse events. All subjects will continue to be followed for overall survival during the long-term follow-up phase.

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Cancer Carcinoma	Biological: Autologous Genetically modified T cells, MAGEA10ᶜ⁷⁹⁶T	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

28 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Dose Escalation Open Label Clinical Trial Evaluating the Safety and Efficacy of MAGE A10ᶜ⁷⁹⁶T in Subjects With Stage IIIb or Stage IV Non-Small Cell Lung Cancer (NSCLC)

Actual Study Start Date :

Nov 1, 2015

Actual Primary Completion Date :

Mar 11, 2020

Actual Study Completion Date :

Mar 17, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Autologous Genetically modified T cells, MAGEA10ᶜ⁷⁹⁶T	Biological: Autologous Genetically modified T cells, MAGEA10ᶜ⁷⁹⁶T

Arm

Intervention/Treatment

Experimental: Autologous Genetically modified T cells, MAGEA10ᶜ⁷⁹⁶T

Biological: Autologous Genetically modified T cells, MAGEA10ᶜ⁷⁹⁶T

Outcome Measures

Primary Outcome Measures

Number of subjects with dose-limiting toxicity (DLT) and adverse events (AE), including serious adverse events (SAE) [24 months]
Determine if treatment with autologous genetically modified T cells, (MAGE A10ᶜ⁷⁹⁶T ) is safe and tolerable through assessment of DLTs, AEs, including SAEs; laboratory assessments, including chemistry, hematology, and coagulation; cardiac and pulmonary assessments, including ECG and troponin.

Secondary Outcome Measures

Proportion of subjects with a confirmed Complete Response (CR) or Partial Response (PR) [24 months]
Evaluation of the efficacy of the treatment by assessment of the Overall Response Rate according to RECIST v1.1
Interval between the date of first T cell infusion dose and first documented evidence of CR or PR [24 months]
Evaluation of the efficacy of the treatment by assessment of time to first response
Interval between the date of first documented evidence of CR or PR until first documented disease progression or death due to any cause [24 months]
Evaluation of the efficacy of the treatment by assessment of duration of response
Interval between the date of first documented evidence of SD until first documented disease progression or death due to any cause [24 months]
Evaluation of the efficacy of the treatment by assessment of duration of stable disease
Interval between the date of first T cell infusion and the earliest date of disease progression or death due to any cause [24 months]
Evaluation of the efficacy of the treatment by assessment of progression-free survival
Interval between the date of first T cell infusion and date of disease progression or death due to any cause [24 months]
Evaluation of the efficacy of the treatment by assessment of overall survival
Best Overall Response (BOR) [24 months]
Best Overall Response (BOR), defined as the best response recorded from the date of T cell infusion until disease progression
To evaluate potential gene therapy-related delayed adverse events for 15 years post infusion. [15 years]
Presence of any of the following LTFU AEs: New malignancies New incidence or exacerbation of a pre-existing neurologic disorder New incidence or exacerbation of a prior rheumatologic or other autoimmune disorder New incidence of a hematologic disorder Opportunistic and/or serious infections Unanticipated illness and/or hospitalization deemed related to gene modified cell therapy Persistence of MAGE-A10c796T and replication-competent lentivirus (RCL) over time.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Subject has histologically or cytologically confirmed diagnosis of advanced non-small cell lung cancer (stage IIIB or IV) or recurrent disease
Subject has received at least one line of prior therapy
Subjects with known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase receptor (ALK) or ROS1 gene rearrangements must have failed (progressive disease or unacceptable toxicity) at least one prior EGFR or ALK or ROS1 tyrosine kinase inhibitor, respectively. Subject may have received PD-1 or PDL-1 inhibitors and or chemotherapy. There is no limit on lines of prior anti-cancer therapy (a washout period applies for recent anti-cancer treatments).
Subject has measurable disease according to RECIST v1.1 criteria prior to lymphodepletion.
Subject is HLA-A02:01 or HLA-A02:06 positive.
Subject's tumor (either an archival specimen or a fresh biopsy if archival tissue is unavailable) has been pathologically reviewed by a designated central laboratory confirming MAGE-A10 expression.
Subject has an ECOG Performance Status 0-1 and anticipated life expectancy >6 months prior to apheresis and >3 months prior to lymphodepletion.
Subject is ≥18 to ≤75 years of age
Adequate organ function

Key Exclusion Criteria:

Subject is HLA-A02:05, HLA-B15:01 and/or HLA-B*46:01 positive.
History of chronic or recurrent (within the last year prior to enrollment) severe autoimmune or active immune-mediated disease requiring steroids or other immunosuppressive treatments.
Subject has symptomatic CNS metastases. Subjects with prior history of symptomatic CNS metastasis must have received treatment and be neurologically stable for at least 1 month prior to leukapheresis and lymphodepletion.
Active malignancy besides NSCLC within 3 years prior to screening.
Uncontrolled intercurrent illness including, but not limited to:

Ongoing or active infection;
Clinically significant cardiac disease
Inadequate pulmonary function
Interstitial lung disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010
2	Stanford Cancer Center	Palo Alto	California	United States	94304
3	University of Miami Sylvester Comprehensive Cancer Center	Miami	Florida	United States	33136
4	H. Lee Moffitt Cancer Center	Tampa	Florida	United States	33612
5	Winship Cancer Institute of Emory University	Atlanta	Georgia	United States	30322
6	Indiana University Simon Cancer Center	Indianapolis	Indiana	United States	46033
7	University of Maryland, Greenebaum Cancer Center	Baltimore	Maryland	United States	21157
8	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
9	Washington University, School of Medicine	Saint Louis	Missouri	United States	63110
10	Duke University Medical Center, Duke Cancer Institute	Durham	North Carolina	United States	27710
11	Ohio State University Wexner Medical Center	Columbus	Ohio	United States	43210
12	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
13	Tennessee Oncology- Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
14	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
15	Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M5G1X6
16	Hospital Universitario Fundación Jiménez Díaz	Madrid		Spain	28040
17	Hospital Universitario 12 Octubre Avda. de Córdoba s/n	Madrid		Spain	28041
18	University College Hospital Macmillan Cancer Centre	London		United Kingdom	WC1E 6AG
19	The Christie NHS Foundation Trust	Manchester		United Kingdom	M20 4BX