Clinical trial NCT02592577: MAGE A10ᶜ⁷⁹⁶T for Advanced NSCLC
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non-Small Cell Lung Cancer
Carcinoma
Keywords: Previously Treated
Cell Therapy
T Cell Therapy
MAGE-A10
Immuno-oncology
T Cell Receptor
Metastatic
Lead sponsor: Adaptimmune
Sponsor class: INDUSTRY
First posted: 2015-10-30
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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-A\*02:01 and/or HLA-A\*02:06 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.


Eligibility criteria: Key Inclusion Criteria:

1. Subject has histologically or cytologically confirmed diagnosis of advanced non-small cell lung cancer (stage IIIB or IV) or recurrent disease
2. Subject has received at least one line of prior therapy
3. 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).
4. Subject has measurable disease according to RECIST v1.1 criteria prior to lymphodepletion.
5. Subject is HLA-A\*02:01 or HLA-A\*02:06 positive.
6. 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.
7. Subject has an ECOG Performance Status 0-1 and anticipated life expectancy \>6 months prior to apheresis and \>3 months prior to lymphodepletion.
8. Subject is ≥18 to ≤75 years of age
9. Adequate organ function

Key Exclusion Criteria:

1. Subject is HLA-A\*02:05, HLA-B\*15:01 and/or HLA-B\*46:01 positive.
2. 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.
3. 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.
4. Active malignancy besides NSCLC within 3 years prior to screening.
5. Uncontrolled intercurrent illness including, but not limited to:

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

Primary outcomes:
measure: Number of subjects with dose-limiting toxicity (DLT) and adverse events (AE), including serious adverse events (SAE)
timeFrame: 24 months
Secondary outcomes:
measure: Proportion of subjects with a confirmed Complete Response (CR) or Partial Response (PR)
timeFrame: 24 months
measure: Interval between the date of first T cell infusion dose and first documented evidence of CR or PR
timeFrame: 24 months
measure: Interval between the date of first documented evidence of CR or PR until first documented disease progression or death due to any cause
timeFrame: 24 months
measure: Interval between the date of first documented evidence of SD until first documented disease progression or death due to any cause
timeFrame: 24 months
measure: Interval between the date of first T cell infusion and the earliest date of disease progression or death due to any cause
timeFrame: 24 months
measure: Interval between the date of first T cell infusion and date of disease progression or death due to any cause
timeFrame: 24 months
measure: Best Overall Response (BOR)
timeFrame: 24 months
measure: To evaluate potential gene therapy-related delayed adverse events for 15 years post infusion.
timeFrame: 15 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Center
state: California
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University Simon Cancer Center
state: Indiana
city: Baltimore
country: United States
facility: University of Maryland, Greenebaum Cancer Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University, School of Medicine
state: Missouri
city: Durham
country: United States
facility: Duke University Medical Center, Duke Cancer Institute
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology- Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 Octubre Avda. de Córdoba s/n
city: London
country: United Kingdom
facility: University College Hospital Macmillan Cancer Centre
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
Study officials:
affiliation: H. Lee Moffitt Cancer Center
name: Ben Creelan, MD, MS
role: STUDY_CHAIR
References:
citation: Blumenschein GR, Devarakonda S, Johnson M, Moreno V, Gainor J, Edelman MJ, Heymach JV, Govindan R, Bachier C, Doger de Speville B, Frigault MJ, Olszanski AJ, Lam VK, Hyland N, Navenot JM, Fayngerts S, Wolchinsky Z, Broad R, Batrakou D, Pentony MM, Sanderson JP, Gerry A, Marks D, Bai J, Holdich T, Norry E, Fracasso PM. Phase I clinical trial evaluating the safety and efficacy of ADP-A2M10 SPEAR T cells in patients with MAGE-A10+ advanced non-small cell lung cancer. J Immunother Cancer. 2022 Jan;10(1):e003581. doi: 10.1136/jitc-2021-003581.