Repare Therapeutics Announces Positive Results of the Lunresertib and Camonsertib Combination from the MYTHIC Phase 1 Gynecologic Expansion Clinical Trial
Repare Therapeutics (RPTX) reported positive results from its MYTHIC Phase 1 gynecologic expansion trial combining lunresertib and camonsertib (Lunre+Camo). The trial showed a 25.9% overall response rate in endometrial cancer and 37.5% in platinum-resistant ovarian cancer. Nearly half of patients maintained progression-free survival at 24 weeks.
The study included heavily pretreated patients, with many receiving the treatment as fourth line or beyond. In endometrial cancer patients, 100% had prior platinum therapy and 77.8% received immune checkpoint inhibitors. For ovarian cancer patients, all were platinum-resistant or ineligible, with 45.8% having received prior PARP inhibitors.
The company plans to initiate a registrational Phase 3 trial for endometrial cancer in second half of 2025.
Repare Therapeutics (RPTX) ha riportato risultati positivi dal suo trial di espansione MYTHIC di Fase 1 che combina lunresertib e camonsertib (Lunre+Camo). Il trial ha mostrato un 25,9% di tasso complessivo di risposta nel carcinoma endometriale e 37,5% nel carcinoma ovarico resistente al platino. Quasi la metà dei pazienti ha mantenuto la sopravvivenza libera da progressione a 24 settimane.
Lo studio ha incluso pazienti fortemente già trattati, con molti che hanno ricevuto il trattamento come quarta linea o oltre. Nei pazienti con carcinoma endometriale, il 100% aveva ricevuto precedentemente terapia con platino e il 77,8% ha ricevuto inibitori del checkpoint immunitario. Per i pazienti con carcinoma ovarico, tutti erano resistenti al platino o non idonei, con il 45,8% che aveva ricevuto precedentemente inibitori PARP.
L'azienda prevede di avviare un trial registrativo di Fase 3 per il carcinoma endometriale nella seconda metà del 2025.
Repare Therapeutics (RPTX) informó resultados positivos de su ensayo de expansión MYTHIC de Fase 1 que combina lunresertib y camonsertib (Lunre+Camo). El ensayo mostró una tasa de respuesta total del 25,9% en el cáncer endometrial y un 37,5% en el cáncer de ovario resistente al platino. Casi la mitad de los pacientes mantuvieron la supervivencia libre de progresión a las 24 semanas.
El estudio incluyó pacientes que habían sido tratados en múltiples ocasiones, con muchos recibiendo el tratamiento como cuarta línea o más. En los pacientes con cáncer endometrial, el 100% había recibido terapia previa con platino y el 77,8% recibió inhibidores de punto de control inmunitario. Para los pacientes con cáncer de ovario, todos eran resistentes al platino o no elegibles, con un 45,8% que había recibido anteriormente inhibidores de PARP.
La compañía planea iniciar un ensayo registrativo de Fase 3 para el cáncer endometrial en la segunda mitad de 2025.
Repare Therapeutics (RPTX)는 lunresertib와 camonsertib (Lunre+Camo)를 결합한 MYTHIC 1상 여성계 확장 시험에서 긍정적인 결과를 보고했습니다. 이 시험은 자궁내막암에서 25.9%의 전체 반응률을 보였고, 플래티넘 저항성 난소암에서 37.5%의 반응률을 나타냈습니다. 환자의 거의 절반이 24주 동안 병의 진행 없이 생존했습니다.
이번 연구는 강력한 치료를 받은 환자를 포함하였으며, 대부분은 4차 이상으로 치료를 받았습니다. 자궁내막암 환자의 경우, 100%가 이전에 플래티넘 요법을 받았고, 77.8%가 면역 체크포인트 억제제를 받았습니다. 난소암 환자들 역시 모두 플래티넘 저항성이거나 비적합했으며, 45.8%는 이전에 PARP 억제제를 받은 경험이 있었습니다.
회사는 2025년 후반에 자궁내막암에 대한 등록용 3상 시험을 시작할 계획입니다.
Repare Therapeutics (RPTX) a annoncé des résultats positifs de son essai d'expansion MYTHIC de phase 1 combinant lunresertib et camonsertib (Lunre+Camo). L'essai a montré un taux global de réponse de 25,9% dans le cancer endométrial et 37,5% dans le cancer de l'ovaire résistant au platine. Près de la moitié des patients ont maintenu une survie sans progression à 24 semaines.
L'étude incluait des patients ayant subi de nombreux traitements, avec beaucoup recevant le traitement en quatrième ligne ou au-delà. Parmi les patients atteints de cancer endométrial, 100% avaient reçu une thérapie au platine au préalable et 77,8% avaient reçu des inhibiteurs de points de contrôle immunitaire. Pour les patients atteints de cancer de l'ovaire, tous étaient résistants au platine ou inéligibles, avec 45,8% ayant reçu des inhibiteurs de PARP auparavant.
La société prévoit de lancer un essai de phase 3 à but d'enregistrement pour le cancer endométrial au deuxième semestre 2025.
Repare Therapeutics (RPTX) berichtete über positive Ergebnisse aus seiner MYTHIC Phase 1 gynäkologischen Erweiterungsstudie, die lunresertib und camonsertib (Lunre+Camo) kombiniert. Die Studie zeigte eine 25,9%ige Gesamtansprechrate bei Endometriumkarzinom und 37,5% bei platinresistentem Eierstockkrebs. Fast die Hälfte der Patienten konnte 24 Wochen lang eine progressionsfreie Überlebenszeit aufrechterhalten.
In der Studie waren stark vorbehandelte Patienten eingeschlossen, wobei viele die Behandlung als vierte Linie oder darüber hinaus erhielten. Bei den Patienten mit Endometriumkarzinom hatten 100% eine vorherige Platintherapie erhalten und 77,8% erhielten Immun-Checkpoint-Inhibitoren. Für die Patienten mit Eierstockkrebs waren alle platinresistent oder nicht geeignet, wobei 45,8% zuvor PARP-Inhibitoren erhalten hatten.
Das Unternehmen plant, in der zweiten Jahreshälfte 2025 eine registrierungsrelevante Phase-3-Studie für Endometriumkarzinom zu starten.
- 25.9% overall response rate in endometrial cancer patients
- 37.5% overall response rate in platinum-resistant ovarian cancer
- 43% progression-free survival at 24 weeks for endometrial cancer
- 45% progression-free survival at 24 weeks for ovarian cancer
- Favorable and differentiated tolerability profile compared to current therapies
- Received positive feedback from both FDA and EMA for development plans
- Phase 3 trial initiation not until second half of 2025
- Most common adverse event was anemia (26.9%, Grade 3)
Insights
The MYTHIC trial data demonstrates compelling clinical efficacy for the Lunre+Camo combination in both endometrial and platinum-resistant ovarian cancers. The 25.9% ORR in endometrial cancer and 37.5% ORR in PROC are particularly noteworthy given the heavily pretreated patient population. The durability of response, with nearly half of patients maintaining progression-free survival at 24 weeks, suggests meaningful clinical benefit. The biomarker-driven approach targeting specific mutations (CCNE1, FBXW7, PPP2R1A) shows promise in patient selection.
The safety profile appears manageable, with anemia being the primary concern at
This positive clinical data significantly strengthens Repare's market position in the gynecologic cancer space. The planned Phase 3 trial initiation in 2H 2025 provides a clear pathway to commercialization. With both FDA and EMA guidance secured, regulatory risks appear well-managed. The biomarker-driven approach could enable premium pricing if approved, particularly given the unmet need in these patient populations.
For a company with a market cap of
Heavily-pretreated patients on lunresertib and camonsertib combination achieved
Nearly half of patients with gynecologic cancers maintained progression-free survival at 24 weeks, comparing favorably to current standard of care
Company plans to initiate a registrational Phase 3 trial of lunresertib in combination with camonsertib in endometrial cancer in 2H 2025
Repare to host conference call and webcast today at 4:30 p.m. ET to discuss these results
Lunresertib is a first-in-class precision oncology small molecule PKMYT1 inhibitor which targets cell cycle regulation in Lunre BM+ tumors (CCNE1 amplifications or FBXW7 or PPP2R1A deleterious alterations). Camonsertib is a potential best-in-class oral small molecule inhibitor of ATR, a critical component of the DNA damage response pathway.
“We are encouraged by the strong response and the clear benefit we observed in patients with endometrial and platinum-resistant ovarian cancers in the MYTHIC clinical trial,” said Lloyd M. Segal, President and Chief Executive Officer of Repare. “These patients need new treatment options and our results support the potential for Lunre+Camo to make a real, positive difference if approved, particularly as a chemotherapy alternative. We have positive feedback from regulatory agencies in both the US and
The MYTHIC clinical trial (NCT04855656) is a first-in-human, global, open-label Phase 1 dose-escalation clinical trial to evaluate safety, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of Lunre+Camo in patients with advanced solid tumors. As of the data cut-off date of November 14, 2024, 51 evaluable patients were enrolled in the gynecologic cancer expansion cohort of the MYTHIC trial.
Across all tumor types treated at the optimized RP2D (n=67), Lunre+Camo therapy demonstrated a favorable and differentiated tolerability profile when compared to current and emerging therapies. The most common adverse event was anemia (
Key Cohort Clinical Findings
Endometrial Cancer Patients:
The 27 evaluable patients with endometrial cancer had a median age of 67 years. All patients exhibited high-risk profiles:
-
100% of patients have undergone prior platinum therapy -
77.8% of patients received immune checkpoint inhibitors -
59% of patients received the combination as a fourth line of therapy or beyond -
18.5% of patients had carcinosarcoma -
85% of tumors had p53 mutations - No tumors with microsatellite instability (MSI)-high status were enrolled indicating proficient mismatch repair (pMMR) status
-
Within the Lunre BM+ subset:
56% of tumors had PPP2R1A mutations;22% carried FBXW7 mutations;15% had CCNE1 amplification; and7% of tumors had multiple mutations
Key efficacy outcomes in evaluable patients with endometrial cancer (N=27):
-
ORR was
25.9% (confirmed ORR in 5 out of 7 patients) -
Clinical benefit was observed in
48.1% of patients, with responses frequently occurring after 12 weeks or more -
At the 24-week landmark analysis, nearly half of patients experienced durable clinical benefit (24-week PFS [PFS24w] =
43% [95% CI, 21-63% ])
Platinum-Resistant Ovarian Cancer Patients:
The 24 evaluable patients with PROC had a median age of 63 years. All patients exhibited high-risk profiles:
-
100% of patients were platinum-resistant or platinum ineligible -
45.8% of patients had received prior PARP inhibitors -
70.8% of patients had received prior bevacizumab -
54% of patients received the combination as a fourth line of therapy or beyond -
100% of tumors had p53 mutations -
Within the Lunre BM+ subset:
87.5% of tumors had CCNE1 amplification;4.2% had FBXW7 mutations;4.2% had PPP2R1A mutations; and4.2% of tumors had multiple mutations
Key efficacy outcomes in evaluable patients with PROC (N=24):
-
ORR was
37.5% (confirmed ORR in 4 out of 9 patients) -
Clinical benefit was observed in
79% of patients -
PFS at the 24-week landmark analysis was PFS24w =
45% [95% CI, 22-66% ]
“Those patients with recurrent gynecologic cancers have limited treatment options as tumors often become resistant to standard of care therapy,” said Brian Slomovitz, MD, MS, FACOG, Director, Gynecologic Oncology, Co-chair of the Cancer Research Center, Mount Sinai Medical Center. “They urgently need new treatment options. Repare’s differentiated, biomarker-driven approach addresses this population and may offer a solution. These data support the potential of Lunre+Camo as a new treatment option to fill this unmet need for patients with endometrial and platinum-resistant ovarian cancers.”
Repare has consulted with both the
“The results of the MYTHIC clinical trial increase our confidence in the potential to bring Lunre+Camo to patients living with this aggressive subset of recurrent endometrial cancer,” said Maria Koehler, MD, PhD, Chief Medical Officer of Repare. “We are deeply grateful to the patients and investigators who participated in this trial, and we look forward to building on these promising data through the registrational clinical trials using Lunre+Camo as a potential new standard of care for those patients, if approved.”
Conference Call and Webcast:
Repare will host a conference call and webcast today, December 12, at 4:30 p.m. ET to discuss the results. Repare’s executive management team will be joined by Brian Slomovitz, MD, MS, FACOG, Director, Gynecologic Oncology, Co-chair of the Cancer Research Center, Mount Sinai Medical Center.
To access the call, please dial (646) 357-8785 (
About Repare Therapeutics Inc.
Repare Therapeutics is a leading clinical-stage precision oncology company enabled by its proprietary synthetic lethality approach to the discovery and development of novel therapeutics. The Company utilizes its genome-wide, CRISPR-enabled SNIPRx® platform to systematically discover and develop highly targeted cancer therapies focused on genomic instability, including DNA damage repair. The Company’s pipeline includes lunresertib (also known as
Forward-Looking Statements
This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 and securities laws in
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Investor Relations & Media Contact:
Robin Garner
Vice President and Head of Investor Relations
Repare Therapeutics Inc.
investor@reparerx.com
Source: Repare Therapeutics Inc.
FAQ
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