Trial Outcomes & Findings for Phase I/II Study Evaluating AUTO4 in Patients With T Cell Receptor Beta Constant (TRBC)1 Positive T Cell Lymphoma (NCT NCT03590574)

Twenty patients were enrolled and AUTO4 was manufactured using leukapheresed autologous peripheral blood mononuclear cells. Five patients did not receive AUTO4 infusion. This was due to death in 2 patients, achieving remission with other chemotherapy (1 patient), central nervous system involvement (1 patient) and proceeding to stem cell transplant (1 patient).

Phase I/II Study Evaluating AUTO4 in Patients With T Cell Receptor Beta Constant (TRBC)1 Positive T Cell Lymphoma

To assess the safety and tolerability of AUTO4 administration. The incidence of Grade 3-5 toxicities occurring within 60 days of AUTO4 infusion.

To identify the recommended Phase II dose and maximum tolerated dose (MTD), if an MTD exists, of AUTO4 by monitoring the frequency of DLT of AUTO4 within 28 days of AUTO4 infusion.

All AEs/SAEs were recorded from admission for pre-conditioning chemotherapy (Day -6 relative to AUTO4). Due to the long period between consent and AUTO4 treatment, any AEs/SAEs related to bridging chemotherapy not associated with study procedures did not require reporting as study AEs/SAEs. Any significant events were added to the patient's medical history. All AEs/SAEs related to study procedures (leukapheresis, bone marrow assessments) were reported.

Incidence and severity of opportunistic infections following AUTO4 infusion.

Feasibility of product generation was examined by assessing the number of AUTO4 successfully manufactured as a fraction of the number of patients undergoing leukapheresis (all patients enrolled).

Participants achieving CR per Lugano criteria based on independent central radiology review. The Lugano classification of response by 18F (Fluorine isotope 18)-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (FDG) positron emission tomography (PET)-computed tomography (CT): 1. no uptake or no residual uptake (when used interim) 2. slight uptake, but below blood pool (mediastinum) 3. uptake above mediastinal, but below or equal to uptake in the liver 4. uptake slightly to moderately higher than liver 5. markedly increased uptake or any new lesion (on response evaluation) Non-progressive disease * complete metabolic response - score of 1, 2 or 3 in nodal or extranodal sites with or without a residual mass * partial metabolic response - score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size * stable disease or no metabolic response - score of 4 or 5 with no obvious change in FDG uptake Progressive disease score 4 or 5 in any lesion

DOR was defined as the time from the first observed CR or partial response (PR) to documented disease progression or death due to any cause, for patients who were considered as responders. Patients who received protocol specified anti-cancer treatment post AUTO4 infusion were ignored in the main analysis. Patients who proceeded to stem cell transplantation (SCT) after AUTO4 infusion were censored at the time of SCT (including the conditioning regimen for SCT). Patients who received new non-protocol anticancer therapies other than SCT were censored at the date of last adequate assessment prior to the new therapy. Patients who experienced event after missing two or more scheduled disease assessments were censored at the date of last adequate assessment prior to the event. Data for DOR were pooled for analysis because the number of patients was \<5 for all of the groups and the intended model cannot be built with such a small sample size.

PFS was defined as the time from the first treatment of AUTO4 to documented disease progression/relapse or death due to any cause. If a patient did not have relapse or death due to any reason prior to data cut-off, PFS was censored at the date of the last adequate assessment by default. Patients who received protocol specified anti-cancer treatment post AUTO4 infusion were ignored in the main analysis. Patients who proceeded to SCT after AUTO4 infusion were censored at the time of SCT (including the conditioning regimen for SCT). Patients who received new non-protocol anticancer therapies other than SCT were censored as the date of last adequate assessment prior to the new therapy. Patients who experienced event after missing two or more scheduled disease assessments were censored at the date of last adequate assessment prior to the event

OS was defined as the time from the first treatment of AUTO4 to death due to any cause. Patients who had not died prior to data cut-off or database finalization were censored at the last contact date. Patients who received SCT after AUTO4 infusion were ignored in the main analysis.

Time taken for participants achieving PR or CR per Lugano criteria based on independent central radiology review. The Lugano classification of response by 18F FDG PET-CT: 1. no uptake or no residual uptake (when used interim) 2. slight uptake, but below blood pool (mediastinum) 3. uptake above mediastinal, but below or equal to uptake in the liver 4. uptake slightly to moderately higher than liver 5. markedly increased uptake or any new lesion (on response evaluation) Non-progressive disease: * Complete metabolic response - score of 1, 2, or 3 in nodal or extranodal sites with or without a residual mass * Partial metabolic response - score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size

The time taken for participants achieving CR per Lugano criteria based on independent central radiology review. The Lugano classification of response by 18F-2-fluoro-2-deoxy-D-glucose FDG PET-CT: 1. no uptake or no residual uptake (when used interim) 2. slight uptake, but below blood pool (mediastinum) 3. uptake above mediastinal, but below or equal to uptake in the liver 4. uptake slightly to moderately higher than liver 5. markedly increased uptake or any new lesion (on response evaluation) Non-progressive disease: • Complete metabolic response - score of 1, 2, or 3 in nodal or extranodal sites with or without a residual mass

RQR8/aTRBC1-CAR positive T cells as determined by polymerase chain reaction at a range of time points in the peripheral blood.

Enumeration of circulating T cell receptor beta constant 1 positive T cells assessed by flow cytometry at a range of time points in the peripheral blood.