Announcement • Jul 15
Allogene Therapeutics Publishes Phase 1 Results of Allo-316 in Journal of Clinical Oncology
Allogene Therapeutics published complete Phase 1 data from the TRAVERSE study of ALLO-316 in advanced or metastatic renal cell carcinoma (RCC) in the Journal of Clinical Oncology. ALLO-316, Allogene’s CD70-targeting AlloCAR T investigational therapy incorporating the Dagger technology, achieved robust expansion, tumor infiltration, and durable antitumor activity in a solid tumor setting. Across the full Phase 1 TRAVERSE trial, 51 patients with Stage IV disease were enrolled, of whom 46 received ALLO-316 and had a median follow-up time of 28.8 months. The Phase 1b expansion cohort evaluated the safety and efficacy of the recommended Phase 2 regimen – ALLO-316 at a dose of 80M CAR T cells following a standard FC lymphodepletion regimen (fludarabine (30 mg/m²/day) and cyclophosphamide (500 mg/m²/day) for 3 days). The 22 patients in the Phase 1b safety population all had RCC resistant to immune checkpoint blockers and at least one tyrosine kinase inhibitor (TKI), 82% had received =2 prior TKIs, and 41% had received prior belzutifan. Twenty of these patients received ALLO-316. Sixteen of the ALLO-316-treated patients in Phase 1b had a high CD70 Tumor Proportion Score (TPS =50%). The median time from enrollment to the start of therapy was four days. A single dose of ALLO-316 produced disease control in half of patients in the Phase 1b cohort, with an overall confirmed response rate of 25% and a confirmed response rate of 31% in patients with CD70 TPS =50%. The median duration of response (mDOR) had not been reached (95% CI: 6.9 months to not estimable), with the longest ongoing response exceeding 18 months. Median overall survival in the Phase 1b population was 15.2 months (95% CI: 4.6 months to not estimable) and was not estimable in the CD70-high group (95% CI: 3.2 months to not estimable). CD70+ patients Phase 1b (N=20) n (%): ORR (confirmed CR or PR per RECIST v1.1) 5/20 (25%), CD70 TPS =50% 5/16 (31%), CD70 TPS 0/4 (0). RECIST v1.1, Response Evaluation Criteria in Solid Tumors, version 1.1; TPS, tumor proportion score. The safety profile of ALLO-316 was manageable and consistent with lymphodepletion and an active CAR T product across the full Phase 1 trial. The most frequent Grade =3 events were hematologic. Three previously reported treatment related Grade 5 adverse events occurred in the Phase 1a portion (cardiogenic shock, failure to thrive and sepsis). There were no Grade 5 adverse events in Phase 1b. A higher incidence of IEC-HS was reported in Phase 1b relative to Phase 1a, likely due in part to improved diagnosis and coding implemented during Phase 1b. Most IEC-HS events were mild to moderate and were successfully managed utilizing a protocol-defined diagnostic and management algorithm. TEAEs =20% incidence Phase 1b (N=22): n (%): Any Grades Grade =3: Neutropenia 18 (82%) 18 (82%), White blood cell count decreased 16 (73%) 16 (73%), Anemia 13 (59%) 9 (41%), Fatigue 5 (23%) 0, Nausea 8 (36%) 0, Thrombocytopenia 13 (59%) 7 (32%), Pyrexia 8 (36%) 0, Peripheral edema 8 (36%) 0, ALT increased 7 (32%) 2 (9%), Headache 5 (23%) 0, Arthralgia 8 (36%) 0, AST increased 6 (27%) 2 (9%), Lymphopenia 5 (23%) 5 (23%). AEs of Special Interest Any Grade Grade =3: CRS 15 (68%) 0, Infection 11 (50%) 9 (41%), IEC-HS 8 (36%) 2 (9%), ICANS 4 (18%) 0, Graft-versus-host disease 0 0. Two patients received lymphodepletion but did not receive ALLO-316: one due to progression of disease (altered mental status during lymphodepletion found to be brain metastases on imaging), and one due to liver and kidney failure during lymphodepletion. IEC-HS includes the preferred terms immune effector cell-associated HLH-like syndrome and Hemophagocytic lymphohistiocytosis. One patient experienced Grade 4 IEC-HS based on gastrointestinal bleeding with subsequent improvement; one patient experienced Grade 3 IEC-HS based on hypotension managed without vasopressors with subsequent improvement. The findings also underscore the broader strategic potential of the Dagger technology, which addresses rejection by the patient’s immune system. By targeting CD70-expressing tumor cells as well as CD70-positive alloreactive host T cells, ALLO-316 is designed to support CAR T-cell expansion and persistence without requiring intensified lymphodepletion. In TRAVERSE, this design translated into robust expansion, durable persistence, and evidence of tumor infiltration – core attributes Allogene believes may be applicable across its next-generation clinical and pre-clinical allogeneic CAR T pipeline. ALLO-316 is an AlloCAR T investigational product targeting CD70, which is highly expressed in renal cell carcinoma (RCC). CD70 is also selectively expressed in several cancers, creating the potential for ALLO-316 to be developed across a variety of both hematologic malignancies and solid tumors. The ongoing Phase 1 TRAVERSE trial is designed to evaluate the safety, tolerability, and activity of ALLO-316 in patients with advanced or metastatic clear cell RCC. In October 2024 the U.S. Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation based on the potential of ALLO-316 to address the unmet need for patients with advanced or metastatic RCC. The FDA previously granted Fast Track Designation (FTD) to ALLO-316 in March 2023. In April 2024, the Company announced an award from the California Institute for Regenerative Medicine (CIRM) to support the ongoing TRAVERSE trial with ALLO-316 in RCC. Allogene’s investigational AlloCAR T oncology products utilize Cellectis technologies. The anti-CD70 AlloCAR T program is licensed exclusively from Cellectis by Allogene and Allogene holds global development and commercial rights to this AlloCAR T program.
