Allogene Therapeutics Announces Positive Phase 1 Data Demonstrating the Potential of ALLO-316 in Heavily Pretreated Patients with Advanced Renal Cell Carcinoma at SITC and IKCS
Allogene Therapeutics presented positive Phase 1 TRAVERSE trial data for ALLO-316 in treating advanced renal cell carcinoma (RCC). The trial showed a 50% overall response rate and 33% confirmed response rate in patients with CD70 Tumor Proportion Score ≥50%. Among 39 enrolled patients, 26 were CD70 positive and evaluable for efficacy. The treatment demonstrated a manageable safety profile, with cytokine release syndrome being the most common adverse event. The FDA granted RMAT designation to ALLO-316 for advanced or metastatic RCC treatment. Additional data from the Phase 1b expansion cohort is expected in mid-2025.
Allogene Therapeutics ha presentato dati positivi della fase 1 dello studio TRAVERSE per ALLO-316 nel trattamento del carcinoma renale a cellule chiare (RCC) avanzato. Lo studio ha mostrato un 50% di tasso di risposta globale e un 33% di tasso di risposta confermata nei pazienti con punteggio di proporzione di tumore CD70 ≥50%. Tra i 39 pazienti arruolati, 26 erano CD70 positivi e valutabili per l'efficacia. Il trattamento ha dimostrato un profilo di sicurezza gestibile, con la sindrome da rilascio di citochine come evento avverso più comune. La FDA ha concesso la designazione RMAT ad ALLO-316 per il trattamento del RCC avanzato o metastatico. Ulteriori dati del coorte di espansione della fase 1b sono attesi entro metà 2025.
Allogene Therapeutics presentó datos positivos del ensayo TRAVERSE de fase 1 para ALLO-316 en el tratamiento del carcinoma de células renales (RCC) avanzado. El ensayo mostró una tasa de respuesta global del 50% y una tasa de respuesta confirmada del 33% en pacientes con puntaje de proporción tumoral CD70 ≥50%. De los 39 pacientes inscritos, 26 eran CD70 positivos y evaluables para eficacia. El tratamiento demostró un perfil de seguridad manejable, siendo el síndrome de liberación de citoquinas el evento adverso más común. La FDA otorgó la designación RMAT a ALLO-316 para el tratamiento del RCC avanzado o metastásico. Se esperan datos adicionales del cohorte de expansión de fase 1b para mediados de 2025.
Allogene Therapeutics는 진행성 신세포암(RCC) 치료를 위한 ALLO-316의 1상 TRAVERSE 시험 데이터에서 긍정적인 결과를 발표했습니다. 이 시험은 CD70 종양 비율 점수 ≥50%인 환자에서 50%의 전반적인 반응률과 33%의 확정된 반응률을 보였습니다. 39명의 등록된 환자 중 26명이 CD70 양성이며 효과성을 평가받았습니다. 이 치료는 관리 가능한 안전성 프로파일을 보여주었고, 사이토카인 방출 증후군이 가장 흔한 부작용이었습니다. FDA는 ALLO-316에 대해 진행성 또는 전이성 RCC 치료를 위한 RMAT 지정을 부여했습니다. 2025년 중반까지 1b 확장 집단의 추가 데이터가 기대됩니다.
Allogene Therapeutics a présenté des données positives de l'essai de phase 1 TRAVERSE pour ALLO-316 dans le traitement du carcinome rénal à cellules claires (RCC) avancé. L'essai a montré un taux de réponse global de 50% et un taux de réponse confirmé de 33% chez des patients avec un score de proportion tumorale CD70 ≥50%. Parmi les 39 patients recrutés, 26 étaient CD70 positifs et évaluables pour l'efficacité. Le traitement a démontré un profil de sécurité gérable, la syndrome de libération de cytokines étant l'événement indésirable le plus commun. La FDA a accordé à ALLO-316 la désignation RMAT pour le traitement du RCC avancé ou métastatique. Des données supplémentaires du cohorte d'expansion de phase 1b sont attendues pour mi-2025.
Allogene Therapeutics hat positive Daten aus der Phase-1-Studie TRAVERSE für ALLO-316 zur Behandlung von fortgeschrittenem Nierenzellkarzinom (RCC) präsentiert. Die Studie zeigte eine 50% Gesamtansprechrate und eine 33% bestätigte Ansprache bei Patienten mit einem CD70 Tumorproportionsscore ≥50%. Von 39 eingeschlossenen Patienten waren 26 CD70-positiv und auf Wirksamkeit bewertbar. Die Behandlung zeigte ein handhabbares Sicherheitsprofil, wobei das Zytokinfreisetzungssyndrom das häufigste unerwünschte Ereignis war. Die FDA hat ALLO-316 die RMAT-Designation für die Behandlung von fortgeschrittenem oder metastasiertem RCC erteilt. Zusätzliche Daten aus der Phase-1b-Erweiterungsgruppe werden Mitte 2025 erwartet.
- 50% overall response rate and 33% confirmed response rate in patients with CD70 TPS ≥50%
- 76% of patients with TPS ≥50% experienced tumor burden reduction
- FDA granted RMAT designation for ALLO-316
- Rapid treatment initiation with median 5 days from enrollment to therapy start
- 33% of high TPS patients showed durable responses lasting ≥4 months
- Three Grade 5 treatment-related adverse events reported, including one death from cardiogenic shock
- Two DLT events of autoimmune hepatitis and cardiogenic shock reported
- 62% of patients experienced infection events
- No response in patients with low TPS (<50%)
Insights
This Phase 1 TRAVERSE trial data for ALLO-316 represents a significant breakthrough in solid tumor treatment. The 50% overall response rate and 33% confirmed response rate in CD70 TPS ≥50% patients at DL2 dosing is particularly impressive for heavily pretreated RCC patients. The rapid five-day enrollment-to-treatment timeline demonstrates practical clinical implementation potential.
The safety profile appears manageable, with mostly low-grade CRS (
The FDA's RMAT designation further validates ALLO-316's potential. However, investors should note that while promising, the sample size remains small and longer-term data from the Phase 1b expansion cohort will be crucial.
The efficacy data in CD70-positive RCC patients is compelling, particularly the 76% tumor burden reduction in high TPS patients. The durability of responses, with 33% of high TPS patients showing responses lasting ≥4 months, suggests meaningful clinical benefit. The stratification by CD70 expression levels provides a clear biomarker strategy for patient selection.
The safety profile is encouraging for a cell therapy in solid tumors. The implementation of a diagnostic and management algorithm for IEC-HS while maintaining efficacy addresses a critical safety concern. The observed viral infections (
- Phase 1 TRAVERSE Trial Demonstrated a Single Infusion of ALLO-316 Can Yield an Overall Response Rate of
50% and Confirmed Response Rate of33% in Patients with CD70 Tumor Proportion Score (TPS) of Greater than50% - TRAVERSE Trial Highlights the Ability of CD70 Dagger® Technology to Promote Robust Expansion and Persistence of ALLO-316 with Standard Lymphodepletion, Validating its Potential as the Next Generation Allogeneic Platform
- ALLO-316 Demonstrated a Manageable Safety Profile; Newly Implemented Diagnostic and Management Algorithm Appears Highly Effective in Abating IEC-HS While Preserving CAR T Efficacy
- Data from the TRAVERSE Trial Supported the FDA's Recent RMAT Designation for ALLO-316 as a Potential Treatment for Advanced or Metastatic RCC
SOUTH SAN FRANCISCO, Calif., Nov. 07, 2024 (GLOBE NEWSWIRE) -- 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, 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's (SITC) Annual Meeting. 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.
“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
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 (
Safety: Most Prevalent TEAEs (>
| 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 (
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
About Allogene Therapeutics
Allogene Therapeutics, with headquarters in South San Francisco, is a clinical-stage biotechnology company pioneering the development of allogeneic chimeric antigen receptor T cell (AlloCAR T™) products for cancer and autoimmune disease. Led by a management team with significant experience in cell therapy, Allogene is developing a pipeline of “off-the-shelf” CAR T cell product candidates with the goal of delivering readily available cell therapy on-demand, more reliably, and at greater scale to more patients. For more information, please visit www.allogene.com, and follow @AllogeneTx on X and LinkedIn.
About the California Institute for Regenerative Medicine (CIRM)
At CIRM, we never forget that we were created by the people of California to accelerate stem cell treatments to patients with unmet medical needs, and act with a sense of urgency to succeed in that mission. To meet this challenge, our team of highly trained and experienced professionals actively partners with both academia and industry in a hands-on, entrepreneurial environment to fast-track the development of today’s most promising stem cell technologies. CIRM is one of the world’s largest institutions dedicated to helping people by bringing the future of regenerative medicine closer to reality.
Cautionary Note on Forward-Looking Statements for Allogene
This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. The press release may, in some cases, use terms such as “potential,” “continue,” “plans,” “can,” “will,” “advance,” “suggest,” “appears to,” “promising,” “expected to,” “designed to,” “goal,” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Forward-looking statements are statements that are not historical facts, including statements regarding intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: the future development, timing, and success of clinical trials and product candidates; statements regarding the potential of ALLO-316 as a treatment for patients with advanced renal cell carcinoma (RCC); the potential for CAR T-cell therapy to treat solid tumors; the advancement of Allogene’s Dagger® technology as a next-generation allogeneic platform; the anticipated benefits of a one-time infusion therapy; the potential for ALLO-316 to be developed across both hematologic malignancies and solid tumors; Allogene’s plans to seek additional FDA input for the clinical development of ALLO-316; and Allogene’s ability to deliver cell therapy on-demand, faster, more reliably, and at greater scale to more patients. Various factors may cause material differences between Allogene’s expectations and actual results, including, risks and uncertainties related to the ongoing clinical trial for ALLO-316 and potential adverse effects; the limited nature of our Phase 1 data from our clinical trials and the extent to which such data may or may not be validated in any future clinical trials; uncertainties regarding regulatory interactions, including future feedback from the U.S. Food and Drug Administration and implications of the RMAT designation; risks relating to the development of allogeneic cell therapy and CAR T products; the impact of competitive and market conditions; uncertainties relating to our novel technologies which makes it difficult to predict the time and cost of product candidate development and obtaining regulatory approval; difficulties we may encounter enrolling patients in our clinical trials; we may not be able to demonstrate the safety and efficacy of our product candidates in our clinical trials, which may prevent or delay regulatory approval and commercialization; and uncertainties regarding our ability to obtain additional financing to develop our products and implement our operating plans. These and other risks are discussed in greater detail in Allogene’s filings with the SEC, including without limitation under the “Risk Factors” heading in its Form 10-Q filed for the quarter ended June 30, 2024, filed with the SEC on August 7, 2024. Any forward-looking statements that are made in this press release speak only as of the date of this press release. Allogene assumes no obligation to update the forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.
AlloCAR T™ and Dagger® are trademarks of Allogene Therapeutics, Inc.
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.
Allogene Media/Investor Contact:
Christine Cassiano
EVP, Chief Corporate Affairs & Brand Strategy Officer
Christine.Cassiano@allogene.com
FAQ
What were the response rates for ALLO-316 in the Phase 1 TRAVERSE trial?
What is the safety profile of ALLO-316 in the Phase 1 TRAVERSE trial?
When will additional data from ALLO-316's Phase 1b expansion cohort be available?
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