On November 7, 2024 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) products for cancer and autoimmune disease, reported that it will concurrently present new data from the Phase 1 TRAVERSE trial in an oral presentation at the 2024 International Kidney Cancer Symposium (IKCS) and a poster session at The Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) Annual Meeting (Press release, Allogene, NOV 7, 2024, View Source [SID1234647916]). The trial evaluates ALLO-316, the Company’s first AlloCAR T product candidate for the potential treatment of solid tumors. The ongoing Phase 1 TRAVERSE trial is enrolling patients with advanced or metastatic renal cell carcinoma (RCC) who have progressed following treatment with an immune checkpoint inhibitor and VEGF-targeting therapy. These presentations highlight compelling evidence of CAR T activity and anti-tumor efficacy in 26 patients with RCC tumors known to be CD70 positive who were evaluable for efficacy outcomes.

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"ALLO-316, the leading "off-the-shelf" CAR T product candidate currently in development for solid tumors, continues to show remarkable potency in the TRAVERSE trial. Data from the Phase 1 study demonstrating significant anti-tumor activity in patients with metastatic disease resistant to multiple therapeutic classes, even with standard lymphodepletion, potentially marks a major advancement in the field," said Zachary Roberts, M.D., Ph.D., EVP, Research and Development and Chief Medical Officer of Allogene. "The unprecedented cell expansion and persistence driven by CD70 CAR-intrinsic Dagger technology, along with strong evidence of tumor infiltration by CAR T cells, highlights the distinctive features of ALLO-316. We believe these findings from our Phase 1 trial lay the groundwork for a new generation of allogeneic cell therapies."

As of the October 14, 2024 data cutoff, 39 patients had been enrolled in the ongoing Phase 1 trial, of which 26 were confirmed to have CD70 positive RCC and were evaluable for efficacy outcomes. The median time from enrollment to the start of therapy was five days. Data from dose escalation cohorts and ongoing Phase 1b expansion cohort are included in the presentations. The Phase 1b expansion cohort is evaluating safety and efficacy of ALLO-316 at DL2 (80M CAR T cells) following a standard FC500 (fludarabine (30 mg/m2/day) and cyclophosphamide (500 mg/m2/d) for 3 days) lymphodepletion regimen. The Phase 1b expansion cohort is expected to ultimately include approximately 20 patients. Additional data from the Phase 1b expansion cohort is expected to be announced in mid-2025.

Following a single infusion of ALLO-316 in heavily pretreated patients, the trial demonstrated best Overall Response Rate (ORR) of 50% and Confirmed Response Rate of 33% in those patients with CD70 Tumor Proportion Score (TPS) of ≥50% who received DL2. Patients with a TPS of ≥50% comprise the majority of patients with advanced or metastatic RCC. Of those with a TPS ≥50, 76% (16/21) experienced a reduction in tumor burden. Two of six (33%) patients with high TPS who received the Phase 1b expansion regimen showed durable responses ongoing at ≥4 months.

Response Rates by CD70 Status and Dose

Patients Evaluable for Disease Outcomesa (N=34)
CD70 Positive (N=26)

CD70 Negative
or Unknown
(N=8)
All
(N=26) FCAb
(N=8) FCc
(N=18) DL2 FC500
(Phase 1b)
(N=8)
Best overall response,d n/N (%)
High TPS (≥50)
Low TPS (<50) 7/26 (27)
7/21 (33)
0/5 (0) 1/8 (13)
1/6 (17)
0/2 (0) 6/18 (33)
6/15 (40)
0/3 (0) 3/8 (38)
3/6 (50)
0/2 (0) 0/8 (0)
NA
NA
Confirmed ORR,e n/N (%)
High TPS (≥50)
Low TPS (<50) 5/26 (19)
5/21 (24)
0/5 (0) 1/8 (13)
1/6 (17)
0/2 (0) 4/18 (22)
4/15 (27)
0/3 (0) 2/8 (25)
2/6 (33)
0/2 (0) 0/8 (0)
NA
NA
aPatients evaluable for disease outcome includes those who received ALLO-316 and had at least one tumor assessment.
bStandard fludarabine and cyclophosphamide plus ALLO-647
cIncludes FC300 and FC500
dBest overall response across visits did not require confirmation for CR/PR.
eConfirmed overall response of CR/PR required confirmation at the subsequent visit.

The most common all-grade adverse events were cytokine release syndrome (CRS) (with only one grade ≥3), fatigue (59%), neutropenia (56%), decreased white blood cell count (54%), anemia (51%) and nausea (51%). Immune effector cell-associated neurotoxicity syndrome (ICANS) was minimal at 8% and no graft-versus-host disease (GvHD) occurred.

Safety: Most Prevalent TEAEs (>40% Any Grade Incidence) and AESI

Adverse Event, n (%) All Patients (N=39) DL2 FC500 (N=11)
All Grades Grade ≥3 All Grades Grade ≥3
Any TEAE 39 (100) 29 (81) 11 (100) 8 (73)
CRS 24 (62) 1 (3) 8 (73) 0
Fatigue 23 (59) 1 (3) 2 (18) 0
Neutropenia 22 (56) 20 (51) 7 (64) 7 (64)
White blood cell count decreased 21/(54) 19 (49) 8 (73) 8 (73)
Anemia 20 (51) 13 (33) 7 (64) 5 (46)
Nausea 20 (51) 0 3 (27) 0
Thrombocytopenia 18 (46) 10 (26) 7 (64) 3 (27)
Pyrexia 16 (41) 2 (5) 4 (36) 0
AEs of Special Interest Any Grade Grade ≥3 Any Grade Grade ≥3
Infectiona
Viral infections 24 (62)
13 (33) 12 (31)
2 (5) 5 (46)
2 (18) 2 (18)
0
Neurotoxicityb
Headache 17 (44)
8 (21) 12 (31)
2 (5) 5 (46)
2 (18) 2 (18)
0
IEC-HS 5 (13) 1 (3) 2 (18) 0
ICANS 3 (8) 0 3 (27) 0
Graft-versus-host disease 0 0 0 0
TEAE included all AEs that started from the first dose date of study drug in each treatment period up to start of another treatment period, death, or the date prior to initiation of another anti-cancer agent, whichever occurred first. IEC-HS includes the preferred terms IEC-HS, HLH, Hemophagocytic lymphohistiocytosis, and atypical HLH. Two patients developed an inflammatory syndrome prior to the existence of IEC-HS as a term in MedDRA, which has been updated as of September 2023.
aInfection events (62%) were primarily low grade; the most common was viral infections (33%) with cytomegalovirus infection and COVID-19 (any grade, 18% and 15%; Grade ≥3, 0% and 5%, respectively).
bNeurotoxicity includes system organ class of nerve system disorders and psychiatric disorders with onset date up to Study Day 30 post ALLO-316 infusion.

Two DLT events of autoimmune hepatitis and cardiogenic shock were reported. Each event occurred in 2 separate participants who received FCA (FC300 plus ALLO-647) lymphodepletion and DL2 of ALLO-316. Three Grade 5 treatment-related adverse events were reported: 1) cardiogenic shock, which was one of the 2 DLT events; 2) sepsis from multi-drug resistant Klebsiella pneumoniae in a participant who received DL4 of ALLO-316. This participant had a prior episode of muscle abscess and bacteremia from the same multi-drug resistant Klebsiella and was receiving anakinra and dexamethasone for hyperinflammation; 3) failure to thrive in a participant 16 months after treatment with ALLO-316. This subject had tumor response of stable disease (SD) at month 12 and no interval scans to evaluate disease status prior to death.

About ALLO-316 (TRAVERSE)
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 a $15 million award from the California Institute for Regenerative Medicine (CIRM) to support the ongoing TRAVERSE trial with ALLO-316 in RCC.