Esophageal Cancer, Gastric Cancer, Gastroesophageal Junction, Head and Neck Cancer, Melanoma, Myxoid Round Cell Liposarcoma, Non-Small Cell Lung Cancer, Ovarian Cancer, Synovial Sarcoma, Urinary Bladder Cancer
Conditions
Keywords
Cell Therapy, T Cell Therapy, SPEAR T Cell, MAGE-A4, Immuno-oncology, Metastatic, Urothelial Cancer, Previously Treated, T Cell Receptor, Squamous, adenosquamous, adenocarcinoma or large cell NSCLC, Squamous or adenocarcinoma esophageal cancer, Sarcoma, Melanoma, Bladder, Ovarian, Radiation therapy
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.
Interventions
GENETICAutologous genetically modified MAGE-A4ᶜ¹º³²T cells
Infusion of autologous genetically modified MAGE-A4ᶜ¹º³²T on Day 1
RADIATIONAutologous genetically modified MAGE-A4c1032T cells combined with low dose radiation
Up to 10 subjects will be considered for Radiation sub-study. Radiation with an intensity of 1.4Gy for 5 days before infusion of MAGE-A4c1032T cells
Sponsors
USWM CT, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Subject is ≥18 to 75 years of age at the time of signing the study informed consent. 2. Subject has histologically confirmed diagnosis of any one of the indicated tumor types 3. Subject is HLA-A\*02 positive. (This determination will be made under screening protocol ADP-0000-001). 4. Subject's tumor shows expression of the MAGE-A4 RNA or protein. (This determination will be made under screening protocol ADP-0000-001). 5. Adequate organ function as indicated in the study protocol 6. Subject has measurable disease according to RECIST v1.1 criteria prior to lymphodepletion 7. 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
1. Subject does not express appropriate HLA-A genotype 2. Subject is receiving excluded therapy/treatment per protocol 3. Subject has symptomatic CNS metastases. 4. Subject has any other active malignancy besides the tumor under study within 3 years prior to Screening. Subject has uncontrolled intercurrent illness. 5. Subject has active infection with HIV, HBV, HCV or HTLV 6. Subject is pregnant or breastfeeding. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events (AE) Including Serious Adverse Events (SAE) | From the start of lymphodepleting chemotherapy until end of interventional phase (up to 3.2 years). | An AE was defined as any untoward medical occurrence in a clinical study participant who received a pharmaceutical product, regardless of causality. An AE was , therefore, any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants with AEs (including SAEs) are presented. |
| Peak Persistence | From afamitresgene autoleucel infusion up to 18 months post-infusion | Peak persistence of afamitresgene autoleucel cells was reported as vector copy numbers per microgram of genomic DNA from peripheral blood mononuclear cell (PBMC). |
| Replication Competent Lentivirus (RCL) | From afamitresgene autoleucel infusion to 3 months post-infusion | The presence of RCL was assessed by quantitative polymerase chain reaction (qPCR) targeting a segment of the vesicular stomatitis virus glycoprotein (VSV-G) coding sequence. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | From afamitresgene autoleucel infusion until disease progression/recurrence (up to 3.2 years) | ORR, defined as the proportion of participants with Best Overall Response (BOR) of confirmed completed response (CR) or partial response (PR) among participants with measurable disease at Baseline. The ORR was based on the assessment of response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by local radiologist. Participants with unknown or missing response were treated as non-responders. |
| Best Overall Response (BOR) | From afamitresgene autoleucel infusion until disease progression/recurrence (up to 3.2 years) | BOR was defined as the best response recorded from the date of T-cell infusion until disease progression. Response categories from best to worst were, confirmed CR, confirmed PR, stable disease (SD), progressive disease (PD), and not evaluable (NE) (per RECIST v1.1) |
| Time to Response (TTR) | From afamitresgene autoleucel infusion until first documented confirmed CR or PR | TTR was defined as the interval between the date of the first T-cell infusion and the earliest date of the first documented confirmed CR or confirmed PR. |
| Duration of Response (DoR) | From initial confirmed response (DR or PR) until PD or censored date. is defined as all participants who had not experienced the event of interest (i.e. ongoing, event free) at the time of the data cut off (used for the analysis). | DoR was measured from the first CR/PR (whichever was first recorded) until the first date of progressive disease. |
| Duration of Stable Disease (DoSD) | From date of afamitresgene autoleucel infusion to first date of radiological PD or censored date | DoSD was defined as the time from the date of T-cell infusion to the first date of the radiological PD. This analysis of DoSD only applied to participants with BOR as confirmed CR, confirmed PR, or confirmed SD. |
| Progression Free Survival (PFS) | From afamitresgene autoleucel infusion until first documented PD or death due to any cause, whichever comes first, or censored date. | PFS was defined as the time from the date of the first T-cell infusion to the first date of the radiological PD or death date (due to any reason), whichever event was earlier. |
| Overall Survival (OS) | From afamitresgene autoleucel infusion until death due to any reason or censored date From afamitresgene autoleucel infusion until death due to any reason or censored date | OS was defined as the time from the date of afamitresgene autoleucel infusion to the date of death (due to any reason). |
Countries
Canada, United States
Contacts
PRINCIPAL_INVESTIGATORDavid Hong, MD
M.D. Anderson Cancer Center
Participant flow
Recruitment details
This was an open-label Phase 1 dose escalation study of afamitresgene autoleucel in HLA-A\*02 positive participants with MAGE-A4 expressing unresectable locally advanced or metastatic cancer of the following types: urothelial, melanoma, head and neck, ovarian, NSCLC, esophageal (squamous and adenocarcinoma), gastric, synovial sarcoma, or MRCLS. This study had a substudy component that investigated the safety and tolerability of afamitresgene autoleucel in combination with low dose radiation.
Pre-assignment details
The main study could enroll up to 18 participants in the dose escalation phase (data cut off 01Sep2020). Following the dose escalation phase, the study was expanded to enroll up to approximately 30 participants at the selected dose range (inclusive of those treated during dose escalation at that dose range) across all the eligible tumor types to better characterize and assess overall safety. The sub study planned to enroll up to 10 participants (data cut off 13Jan2022).
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 38 Participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 1 / 3 | 15 / 32 | 2 / 4 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 32 / 32 | 4 / 4 |
| serious Total, serious adverse events | 2 / 3 | 2 / 3 | 23 / 32 | 3 / 4 |
Outcome results
None listed