On May 29, 2020 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) therapies for cancer, in collaboration with development partner Servier, an independent international pharmaceutical company, reported positive initial results from Allogene’s dose escalation Phase 1 ALPHA study of ALLO-501 in relapsed/refractory non-Hodgkin lymphoma (NHL) (Press release, Allogene, MAY 29, 2020, View Source [SID1234558697]). Data were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting. This study utilizes ALLO-647, Allogene’s anti-CD52 monoclonal antibody (mAb), as a part of its differentiated lymphodepletion regimen.

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"We are very pleased with these initial Phase 1 results, which indicated that ALLO-501 and ALLO-647 were well tolerated and produced complete responses in patients with advanced NHL," said David Chang, M.D., Ph.D., President, Chief Executive Officer and Co-Founder of Allogene. "Based on these results, we believe we are on the right trajectory to make AlloCAR T therapy a reality for patients."

"Allogeneic CAR T therapies provide an off-the-shelf option that may make cellular therapies available to more patients," said Sattva S. Neelapu, M.D., Professor, Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center in Houston, Texas. "While longer follow-up is required, the response to ALLO-501 appears promising with 75% of patients remaining in response. Together with the positive safety profile, these data suggest that ALLO-501 has the potential to be an effective option if confirmed in future studies."

As of the May 2020 data cutoff, 23 patients were enrolled and 22 patients received ALLO-501. One patient was removed from the study prior to lymphodepletion due to acute renal failure from urinary obstruction. The median time from enrollment to the start of therapy was five days.

For the efficacy analysis, 19 out of 22 patients reached at least one month assessment as of the May 2020 data cutoff. Responses were observed across all cell doses and tumor histologies (diffuse large B-cell lymphoma and follicular lymphoma) with an overall response rate (ORR) of 63% and complete response (CR) rate of 37%. Higher dose ALLO-647 was associated with a higher CR rate of 50%, deeper lymphodepletion and delayed host T cell recovery. With a median follow-up of 3.8 months, nine of the 12 responding patients (75%) remain in response as of the data cutoff.

Cell Dose
and LD
regimen 39mg ALLO-647 90mg ALLO-647 All Patients
(N=19)
(95% CI)
40 x 106
CAR+ cells
(N=4) 120 x 106
CAR+ cells
(N=4) 360 x 106
CAR+ cells
(N=3) All 39mg
ALLO-647
(N=11) 120 x 106
CAR+ cells
(N=6) 360 x 106
CAR+ cells
(N=2) All 90mg
ALLO-647
(N=8)
ORR, n (%) 3 (75%) 3 (75%) 1 (33%) 7 (64%) 4 (67%) 1(50%) 5 (63%) 12/19 (63%)
(38%, 84%)
CR, n (%) 1 (25%) 1 (25%) 1 (33%) 3 (27%) 4 (67%) 0 (0%) 4 (50%) 7/19 (37%)
(16%, 62%)
One of the ongoing responders is a patient with an initial partial response (PR) who progressed by month two. This patient achieved a CR after re-treatment with the same dose of ALLO-501 and higher dose (90mg) ALLO-647. This patient is reflected as a PR in the table above and not as a CR.

Included in the overall efficacy analysis are three patients who were refractory to prior autologous CAR T therapy (the best response of progressive disease or disease progression within three months). These patients were also refractory to AlloCAR T therapy. In CAR T naïve patients, the ORR was 75% and the CR rate was 44%.

All Cell Doses +
39mg ALLO-647
(N=10) 120 x 106 and 360 x 106 CAR+ cells +
90mg ALLO-647
(N=6) All CAR T Naïve Patients
(N=16)
ORR, n (%) 7 (70%) 5 (83%) 12/16 (75%)
(48%, 93%)
CR, n (%) 3 (30%) 4 (67%) 7/16 (44%)
(20%, 70%)
No dose limiting toxicities, graft-vs-host disease, or Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) was observed.

Adverse Events of Interest Grade 1
N (%) Grade 2
N (%) Grade 3
N (%) Grade 4
N (%) Grade 5
N (%)
Cytokine Release Syndrome 2 (9%) 4 (18%) 1 (5%) - -
ICANS - - - - -
Graft-versus-Host Disease - - - - -
Infection 5 (23%) 4 (18%) 2 (9%) - -
Infusion Reaction 1 (5%) 9 (41%) 1 (5%) - -
Neutropenia - 1 (5%) 7 (32%) 7 (32%) -
Cytokine release syndrome occurred in 32% of the patients, was mainly mild to moderate in severity, manageable with standard recommendations, and all events resolved within a maximum of seven days. Patients treated with 90mg ALLO-647 did not experience an increase in infection as compared to those treated with 39mg ALLO-647.

Four patients (18%) experienced serious adverse events (SAE). One patient had Grade 2 pyrexia and Grade 2 cytomegalovirus (CMV) reactivation which resolved in two days and six days, respectively. One patient had Grade 3 rotavirus infection and Grade 3 hypokalemia which resolved in 15 days and two days, respectively. One patient had Grade 3 febrile neutropenia and Grade 3 hypotension which each resolved in two days. One patient had a Grade 3 upper GI hemorrhage which resolved in one day and Grade 3 CMV reactivation which resolved in 25 days.

Adverse events were observed across all dose levels of ALLO-501 and ALLO-647. SAEs were observed at ALLO-501 cell dose level 40 x 106 and 120 x 106 and at both dose levels of ALLO-647.

"We are pleased to see the progress made by Allogene in the ALPHA trial and the positive initial data for ALLO-501," said Olivier Laureau, President of Servier. "Our teams are proud to play a role in helping to develop innovative therapies for patients in need."

Allogene is the sponsor of the Phase 1 ALPHA trial which is designed to assess the safety and tolerability at increasing dose levels of ALLO-501 and ALLO-647 in the most common NHL subtypes of relapsed/refractory diffuse large B-cell lymphoma or follicular lymphoma.

ALLO-501A is a next generation anti-CD19 AlloCAR T devoid of the rituximab recognition domains found in ALLO-501. This could allow for use in a broader patient population, including those NHL patients with recent rituximab exposure. ALLO-501A is intended for Phase 2 development and enrollment has been initiated in the Phase 1 portion of the ALPHA2 trial of ALLO-501A.

Webinar
Please register for the webinar on the Company’s website at www.allogene.com under the Investors tab in the News and Events section (View Source) or by clicking the following link directly.

The webinar will be available as a live event only and the materials presented will be available on the Allogene website prior to the start of the event.

About ALLO-501 (Allogene Sponsored)
ALLO-501 is an anti-CD19 allogeneic CAR T (AlloCAR T) therapy being jointly developed under a collaboration agreement between Servier and Allogene based on an exclusive license granted by Cellectis to Servier. ALLO-501 uses Cellectis technologies. Servier grants to Allogene exclusive rights to ALLO-501 in the U.S. while Servier retains exclusive rights for all other countries.