Leap Therapeutics Reports Positive Updated Data from Sirexatamab Colorectal Cancer Study
Leap Therapeutics (LPTX) has reported updated data from Part B of the DeFianCe study, evaluating sirexatamab in combination with bevacizumab and chemotherapy for colorectal cancer (CRC) treatment. The study showed significant improvements in multiple patient groups:
In patients with high DKK1 levels, the treatment demonstrated a 32% higher overall response rate (ORR) and 3.5-month longer progression-free survival (PFS). For patients without prior anti-VEGF therapy, results showed a 22% higher ORR and 2.6-month longer PFS.
The treatment combination was well-tolerated, and 34 patients remain on the sirexatamab experimental arm compared to 24 in the control arm. The company sees a substantial market opportunity, with approximately 30,000 second-line CRC patients in the US and 160,000 in the next 7 largest markets. Leap plans to proceed with a registrational Phase 3 trial and has engaged financial advisors to explore business development opportunities.
Leap Therapeutics (LPTX) ha riportato dati aggiornati dalla Parte B dello studio DeFianCe, che valuta il sirexatamab in combinazione con bevacizumab e chemioterapia per il trattamento del cancro colorettale (CRC). Lo studio ha mostrato significativi miglioramenti in diversi gruppi di pazienti:
Nei pazienti con alti livelli di DKK1, il trattamento ha dimostrato un tasso di risposta complessivo (ORR) superiore del 32% e una sopravvivenza libera da progressione (PFS) più lunga di 3,5 mesi. Per i pazienti senza terapia anti-VEGF precedente, i risultati hanno mostrato un ORR superiore del 22% e un PFS più lungo di 2,6 mesi.
La combinazione di trattamenti è stata ben tollerata, e 34 pazienti rimangono nel braccio sperimentale di sirexatamab rispetto ai 24 nel braccio di controllo. L'azienda vede un'opportunità di mercato sostanziale, con circa 30.000 pazienti di CRC di seconda linea negli Stati Uniti e 160.000 nei prossimi 7 maggiori mercati. Leap prevede di procedere con uno studio registrativo di Fase 3 e ha coinvolto consulenti finanziari per esplorare opportunità di sviluppo commerciale.
Leap Therapeutics (LPTX) ha informado datos actualizados de la Parte B del estudio DeFianCe, que evalúa el sirexatamab en combinación con bevacizumab y quimioterapia para el tratamiento del cáncer colorrectal (CRC). El estudio mostró mejoras significativas en múltiples grupos de pacientes:
En pacientes con altos niveles de DKK1, el tratamiento demostró una tasa de respuesta global (ORR) un 32% más alta y una supervivencia libre de progresión (PFS) 3.5 meses más larga. Para los pacientes sin terapia anti-VEGF previa, los resultados mostraron un ORR un 22% más alto y un PFS 2.6 meses más largo.
La combinación de tratamientos fue bien tolerada, y 34 pacientes permanecen en el brazo experimental de sirexatamab en comparación con 24 en el brazo de control. La empresa ve una oportunidad de mercado sustancial, con aproximadamente 30,000 pacientes de CRC de segunda línea en EE. UU. y 160,000 en los próximos 7 mercados más grandes. Leap planea proceder con un ensayo de Fase 3 registracional y ha contratado asesores financieros para explorar oportunidades de desarrollo empresarial.
Leap Therapeutics (LPTX)는 대장암(CRC) 치료를 위한 베바시주맙 및 화학요법과 함께 시렉사타맙을 평가하는 DeFianCe 연구의 B 부분에서 업데이트된 데이터를 보고했습니다. 이 연구는 여러 환자 그룹에서 유의미한 개선을 보여주었습니다:
높은 DKK1 수준을 가진 환자에서 치료는 32% 높은 전체 반응률(ORR)과 3.5개월 더 긴 무진행 생존기간(PFS)을 나타냈습니다. 이전에 항-VEGF 치료를 받지 않은 환자에게서는 ORR이 22% 더 높고 PFS가 2.6개월 더 길었습니다.
치료 조합은 잘 견뎌졌으며, 34명의 환자가 시렉사타맙 실험군에 남아 있는 반면, 대조군에는 24명이 남아 있습니다. 이 회사는 미국에서 약 30,000명의 2차 대장암 환자와 다음 7개 주요 시장에서 160,000명의 환자가 있는 상당한 시장 기회를 보고 있습니다. Leap은 등록 Phase 3 시험을 진행할 계획이며, 사업 개발 기회를 탐색하기 위해 재무 자문가를 고용했습니다.
Leap Therapeutics (LPTX) a rapporté des données mises à jour de la Partie B de l'étude DeFianCe, évaluant le sirexatamab en combinaison avec le bevacizumab et la chimiothérapie pour le traitement du cancer colorectal (CRC). L'étude a montré des améliorations significatives dans plusieurs groupes de patients :
Chez les patients ayant des niveaux élevés de DKK1, le traitement a démontré un taux de réponse global (ORR) supérieur de 32 % et une survie sans progression (PFS) plus longue de 3,5 mois. Pour les patients sans thérapie anti-VEGF préalable, les résultats ont montré un ORR supérieur de 22 % et une PFS plus longue de 2,6 mois.
La combinaison de traitements a été bien tolérée, et 34 patients restent dans le bras expérimental de sirexatamab par rapport à 24 dans le bras témoin. L'entreprise voit une opportunité de marché substantielle, avec environ 30 000 patients de CRC en deuxième ligne aux États-Unis et 160 000 dans les 7 plus grands marchés suivants. Leap prévoit de procéder à un essai de Phase 3 d'enregistrement et a engagé des conseillers financiers pour explorer des opportunités de développement commercial.
Leap Therapeutics (LPTX) hat aktualisierte Daten aus Teil B der DeFianCe-Studie veröffentlicht, die sirexatamab in Kombination mit Bevacizumab und Chemotherapie zur Behandlung von kolorektalem Krebs (CRC) bewertet. Die Studie zeigte signifikante Verbesserungen in mehreren Patientengruppen:
Bei Patienten mit hohen DKK1-Spiegeln zeigte die Behandlung eine um 32 % höhere Gesamtansprechrate (ORR) und eine um 3,5 Monate längere progressionsfreie Überlebenszeit (PFS). Bei Patienten ohne vorherige Anti-VEGF-Therapie zeigten die Ergebnisse eine um 22 % höhere ORR und eine um 2,6 Monate längere PFS.
Die Behandlungskombination wurde gut vertragen, und 34 Patienten bleiben in der experimentellen Gruppe mit sirexatamab im Vergleich zu 24 in der Kontrollgruppe. Das Unternehmen sieht eine erhebliche Marktchance, mit etwa 30.000 CRC-Patienten in der zweiten Linie in den USA und 160.000 in den nächsten 7 größten Märkten. Leap plant, mit einer registrierenden Phase-3-Studie fortzufahren und hat Finanzberater engagiert, um Geschäftsmöglichkeiten zu erkunden.
- Statistically significant 32% higher ORR and 3.5-month longer PFS in high DKK1 patients
- 22% higher ORR and 2.6-month longer PFS in patients without prior anti-VEGF therapy
- Well-tolerated safety profile consistent with previous studies
- Large market opportunity with 30,000 US patients and 160,000 in next 7 largest markets
- More patients remaining on sirexatamab treatment vs control arm (34 vs 24)
- Primary endpoint of PFS in intent-to-treat population still not mature
- Overall survival data not yet mature in non-VEGF therapy group
- Additional Phase 3 trial required before potential approval
Insights
These updated DeFianCe study results represent a meaningful clinical advancement for Leap's sirexatamab in colorectal cancer (CRC). The statistically significant 32% higher ORR and 3.5-month PFS improvement in high DKK1 patients is particularly notable, as it demonstrates strong target engagement and validates the drug's mechanism of action.
The biomarker-driven approach is scientifically sound – selecting patients with high DKK1 levels creates a precision medicine opportunity in CRC, where new targeted options are desperately needed. Similarly, the 22% higher ORR in anti-VEGF naive patients suggests an important treatment sequencing consideration that could influence clinical practice.
What's particularly encouraging is the trial's design quality. Having both investigator-assessed and blinded independent central review data adds credibility, while the continued maturation showing favorable trends indicates durable benefit. The safety profile remains consistent with prior studies, which is critical for a second-line therapy where patient quality of life is paramount.
With 34 patients still on the experimental arm versus 24 on control, the survival curves should continue separating, potentially strengthening the statistical significance. The data clearly justifies advancing to Phase 3, and the identified patient populations provide a well-defined regulatory pathway focused on those most likely to benefit.
This data release substantially derisks Leap's sirexatamab program and creates multiple potential value inflection points. The company has effectively identified two distinct patient populations where sirexatamab shows superior efficacy – providing optionality for the Phase 3 program design and commercial strategy.
The market opportunity outlined is substantial – targeting 25-50% of the 30,000 US second-line CRC patients and corresponding international markets. More importantly, the potential expansion into first-line treatment would dramatically increase the addressable market to 45,000 US patients, significantly amplifying commercial potential.
The engagement of a financial advisor to explore business development opportunities is strategically timed after positive data and could accelerate several scenarios: a partnership deal to fund the costly Phase 3 program, licensing arrangements in certain territories, or potentially an acquisition given Leap's relatively small
With a Phase 3 trial on the horizon, Leap has reached a critical milestone that typically attracts institutional investor interest. The biomarker strategy is particularly compelling as it allows for a potentially smaller, more targeted pivotal trial with higher probability of success. The combination of statistical significance across multiple endpoints, clear patient selection strategy, and large market opportunity positions sirexatamab as Leap's most valuable asset with meaningful differentiation in the competitive landscape.
Updated data confirms statistically significant
in second-line CRC patients with high
Statistically significant
in patients who had not had prior anti-VEGF therapy
Leap to host a conference call to present clinical data today, March 26, 2025, at 8:00 a.m. ET
"The updated data from Part B of the DeFianCe study presented today confirms that sirexatamab can generate significantly higher ORR and longer PFS in CRC patients who have high levels of
DeFianCe Study Update
- In patients with high
DKK1 levels (upper quartile, n=44), the sirexatamab Experimental Arm has a statistically significant32% higher ORR, 3.5 month longer PFS, and OS compared to the Control Arm:
Sirexatamab (n=25) | Control Arm (n=19) | ||
ORR by IA | 48.0 % | 15.8 % | p = 0.0067 |
ORR by BICR | 40.0 % | 5.3 % | p < 0.001 |
Median PFS | 9.36 months | 5.88 months | HR 0.46 p = 0.0248 |
Median OS | Not Yet Reached | 9.49 months | HR 0.09 p = 0.0018 |
Patients on study drug | 10 | 1 |
- In patients who had not received prior anti-VEGF therapy (n=95), the sirexatamab Experimental Arm has a statisticially significant
22% higher ORR and 2.6 month longer PFS compared to the Control Arm, with OS not mature but favoring the sirexatamab Experimental Arm:
Sirexatamab (n=49) | Control Arm (n=46) | ||
ORR by IA | 55.1 % | 32.6 % | p = 0.0116 |
ORR by BICR | 44.9 % | 21.7 % | p = 0.0066 |
Median PFS | 10.94 months | 8.34 months | HR 0.59 p = 0.0386 |
Median OS | Not Yet Reached | Not Yet Reached | HR 0.22 p = 0.0719 |
Patients on study drug | 23 | 8 |
- Across the intent-to-treat population (n=188), the sirexatamab Experimental Arm has improved ORR compared to the Control Arm, with the primary endpoint of PFS still to mature due to the higher number of patients remaining on sirexatamab driving separation after the median:
Sirexatamab (n=94) | Control Arm (n=94) | ||
ORR by IA | 36.2 % | 25.5 % | p = 0.0536 |
ORR by BICR | 33.0 % | 16.0 % | p = 0.0023 |
Median PFS | 7.82 months | 8.31 months | HR 0.83 p = 0.1809 |
Patients on study drug | 34 | 24 |
- The combination of sirexatamab plus bevacizumab and chemotherapy is well tolerated with a safety profile that is consistent with previous studies.
- The strong signal from the DeFianCe study supports a registrational Phase 3 clinical trial to evaluate sirexatamab plus bevacizumab and chemotherapy in second-line MSS CRC patients with high
DKK1 levels or in patients who have not received prior anti-VEGF therapy. - With approximately 30,000 second-line treated CRC patients in the US and 160,000 in the next 7 largest markets, sirexatamab has a large market opportunity in the 25
-50% of patients who have highDKK1 levels or in the approximately50% of patients who did not receive prior anti-VEGF therapy. In addition, the outcomes in patients with no prior anti-VEGF therapy provides an opportunity to move into treating first-line CRC patients, where there are an estimated 45,000 patients in the US and 265,000 in the next 7 largest markets who receive therapy for their advanced disease. - Leap has engaged a leading financial advisor to explore business development opportunities to further the development of sirexatamab.
Conference Call
- Leap's management team will host a conference call today, March 26, 2025 at 8:00 a.m. Eastern Time to further discuss the data. The conference call will be broadcast live in listen-only mode and can be accessed via the webcast URL: https://edge.media-server.com/mmc/p/t6576mgc. A replay of the event will be available for a limited time on the Investors page of the Company's website at https://investors.leaptx.com/.
About Leap Therapeutics
Leap Therapeutics (Nasdaq: LPTX) is focused on developing targeted and immuno-oncology therapeutics. Leap's most advanced clinical candidate, sirexatamab (DKN-01), is a humanized monoclonal antibody targeting the Dickkopf-1 (
FORWARD-LOOKING STATEMENTS
This press release contains forward-looking statements within the meaning of the federal securities laws. Such statements are based upon current plans, estimates and expectations of the management of Leap that are subject to various risks and uncertainties that could cause actual results to differ materially from such statements. The inclusion of forward-looking statements should not be regarded as a representation that such plans, estimates and expectations will be achieved. Words such as "anticipate," "expect," "project," "intend," "believe," "may," "will," "should," "plan," "could," "continue," "target," "contemplate," "estimate," "forecast," "guidance," "predict," "possible," "potential," "pursue," "likely," and words and terms of similar substance used in connection with any discussion of future plans, actions or events identify forward-looking statements.
All statements, other than historical facts, including statements regarding the potential safety, efficacy, and regulatory and clinical progress of Leap's product candidates; the size of the potential addressable market for sirexatamab, including the number or percentage of patients with advanced CRC that have or are likely to have high levels of
CONTACT:
Douglas E. Onsi
President & Chief Executive Officer
Leap Therapeutics, Inc.
617-714-0360
donsi@leaptx.com
Matthew DeYoung
Investor Relations
Argot Partners
212-600-1902
leap@argotpartners.com
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SOURCE Leap Therapeutics, Inc.
FAQ
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