NuCana Announces Encouraging Initial Data from Phase 1b/2 Modular Study of NUC-3373 in Combination with Pembrolizumab or Docetaxel
NuCana announced initial data from its Phase 1b/2 study of NUC-3373 in combination therapies. In Module 1, combining NUC-3373 with pembrolizumab showed promising results in 12 advanced solid tumor patients, achieving a 22% objective response rate and 67% disease control rate. Notable cases included a bladder cancer patient achieving 100% target lesion reduction and a melanoma patient showing 81% reduction. In Module 2, NUC-3373 with docetaxel demonstrated extended stable disease in lung cancer patients, with one achieving stability for over 13 months. The combinations were generally well-tolerated, though Module 2 enrollment was paused due to docetaxel-related toxicity concerns.
NuCana ha annunciato i dati iniziali del suo studio di Fase 1b/2 su NUC-3373 in terapie combinate. Nel Modulo 1, la combinazione di NUC-3373 con pembrolizumab ha mostrato risultati promettenti in 12 pazienti con tumori solidi avanzati, registrando un tasso di risposta obiettivo del 22% e un tasso di controllo della malattia del 67%. Casi notevoli includevano un paziente con cancro alla vescica che ha raggiunto una riduzione del 100% della lesione target e un paziente con melanoma che ha mostrato una riduzione dell'81%. Nel Modulo 2, NUC-3373 in combinazione con docetaxel ha dimostrato una malattia stabile prolungata nei pazienti con cancro ai polmoni, con uno di essi che ha ottenuto stabilità per oltre 13 mesi. Le combinazioni sono state generalmente ben tollerate, sebbene l'arruolamento nel Modulo 2 sia stato sospeso a causa di preoccupazioni relative alla tossicità legata al docetaxel.
NuCana anunció datos iniciales de su estudio de Fase 1b/2 sobre NUC-3373 en terapias combinadas. En el Módulo 1, la combinación de NUC-3373 con pembrolizumab mostró resultados prometedores en 12 pacientes con tumores sólidos avanzados, logrando una tasa de respuesta objetiva del 22% y una tasa de control de la enfermedad del 67%. Casos notables incluyeron un paciente con cáncer de vejiga que logró una reducción del 100% en la lesión objetivo y un paciente con melanoma que mostró una reducción del 81%. En el Módulo 2, NUC-3373 con docetaxel demostró una enfermedad estable prolongada en pacientes con cáncer de pulmón, uno de los cuales logró estabilidad durante más de 13 meses. Las combinaciones fueron generalmente bien toleradas, aunque la inscripción en el Módulo 2 se detuvo debido a preocupaciones sobre la toxicidad relacionada con el docetaxel.
NuCana는 NUC-3373의 1b/2상 연구 초기 데이터를 발표했습니다. 모듈 1에서 NUC-3373과 펨브롤리주맙을 병용한 결과, 12명의 진행성 고형암 환자에서 22%의 객관적 반응률과 67%의 질병 조절률을 달성하는 유망한 결과를 보였습니다. 특히 방광암 환자는 목표 병변의 100% 감소를 달성하였고, 흑색종 환자는 81% 감소를 보였습니다. 모듈 2에서는 NUC-3373과 도세탁셀의 병용으로 폐암 환자에서 13개월 이상 안정 상태를 유지한 사례가 있었습니다. 이 조합은 일반적으로 잘 견딜 수 있는 결과를 보였으나, 도세탁셀과 관련된 독성 문제로 모듈 2의 등록이 중단되었습니다.
NuCana a annoncé des données initiales de son étude de Phase 1b/2 sur NUC-3373 dans le cadre de thérapies combinées. Dans le Module 1, la combinaison de NUC-3373 avec pembrolizumab a montré des résultats prometteurs chez 12 patients atteints de tumeurs solides avancées, atteignant un taux de réponse objectif de 22% et un taux de contrôle de la maladie de 67%. Parmi les cas notables, un patient atteint d'un cancer de la vessie a obtenu une réduction de 100% de la lésion cible, tandis qu'un patient atteint de mélanome a montré une réduction de 81%. Dans le Module 2, NUC-3373 associé à docétaxel a montré une maladie stable prolongée chez les patients atteints de cancer du poumon, l'un d'eux maintenant sa stabilité pendant plus de 13 mois. Les combinaisons ont généralement été bien tolérées, bien que l'inscription au Module 2 ait été suspendue en raison de préoccupations liées à la toxicité du docétaxel.
NuCana hat erste Daten aus seiner Phase 1b/2-Studie zu NUC-3373 in Kombinationsbehandlungen veröffentlicht. Im Modul 1 zeigte die Kombination von NUC-3373 mit Pembrolizumab vielversprechende Ergebnisse bei 12 Patienten mit fortgeschrittenen soliden Tumoren, mit einer objektiven Ansprechraten von 22% und einer Krankheitskontrollrate von 67%. Bemerkenswerte Fälle beinhalteten einen Blasenkrebspatienten, der eine 100%ige Reduktion der Zielverletzung erzielte, sowie einen Melanompatienten mit einer Reduktion von 81%. Im Modul 2 zeigte NUC-3373 in Kombination mit Docetaxel eine verlängerte stabile Erkrankung bei Lungenkrebspatienten; einer erreichte eine Stabilität von mehr als 13 Monaten. Die Kombinationen wurden im Allgemeinen gut vertragen, obwohl die Einschreibung im Modul 2 aufgrund von Bedenken hinsichtlich der Toxizität von Docetaxel pausiert wurde.
- 22% objective response rate and 67% disease control rate in Module 1
- 100% target lesion reduction in one bladder cancer patient
- 81% reduction in target lesion for melanoma patient
- Extended stable disease duration of 13+ months in a pleural mesothelioma patient
- Demonstrated ability to benefit patients who had exhausted other treatment options
- Module 2 enrollment suspended due to docetaxel toxicity challenges
- Protocol modifications required for Module 2 to consider different taxane options
Insights
The initial Phase 1b/2 data for NUC-3373 combinations shows promising clinical efficacy. The 22% objective response rate and 67% disease control rate in heavily pretreated patients are particularly noteworthy. Two standout cases include a 100% reduction in target lesion for a bladder cancer patient and an 81% reduction for a melanoma patient - both previously resistant to PD-(L)1 therapy.
The durability of responses is impressive, with patients maintaining benefits for 10-13 months. This suggests NUC-3373's potential as a new treatment option for patients who have exhausted standard therapies. The drug's dual mechanism - targeting thymidylate synthase and enhancing immune responses through DAMP release - provides a strong scientific rationale for the observed clinical benefits.
The combination of NUC-3373 with pembrolizumab shows particular promise in PD-(L)1 resistant patients - a significant unmet medical need. The ability to achieve meaningful responses in patients who previously failed checkpoint inhibitor therapy suggests a potential paradigm shift in treatment sequencing. The safety profile appears manageable, though the docetaxel combination requires optimization.
The prolonged stable disease in lung cancer patients (extending to 13 months) is clinically meaningful, considering docetaxel typically provides only 3-4 months of progression-free survival. These results warrant further investigation, particularly given the options for patients who progress after first-line therapy.
Patients with Advanced Solid Tumors who had Exhausted All Other Treatment Options and were PD-(L)1 Experienced Achieved Significant Tumor Volume Reductions and Prolonged Progression Free Survival Following Treatment with NUC-3373 plus Pembrolizumab
One Patient Achieved a
Patients with Lung Cancer who had Exhausted All Other Treatment Options Achieved Prolonged Progression Free Survival Following Treatment with NUC-3373 plus Docetaxel
EDINBURGH, United Kingdom, Nov. 11, 2024 (GLOBE NEWSWIRE) -- NuCana plc (NASDAQ: NCNA) announced that initial data from the ongoing Phase 1b/2 modular study (NuTide:303) investigating NUC-3373 in combination with the PD-1 inhibitor pembrolizumab for patients with advanced solid tumors (Module 1) and in combination with docetaxel for patients with lung cancer (Module 2) have been published in MedRxiv, the preprint server for Health Sciences.
Module 1 included 12 patients with a variety of solid tumors who had exhausted all other treatment options. The majority of patients (n=9) had received prior PD-(L)1 based therapy. Encouraging signals of anti-cancer activity were observed with confirmed Partial Responses in 2 patients and Stable Disease in a further four patients, resulting in an objective response rate of
Module 1 Selected Case Studies: NUC-3373 plus pembrolizumab in patients with advanced solid tumors
- 72-year-old patient with urothelial bladder cancer (Lynch syndrome) who had previously received gemcitabine plus cisplatin followed by the PD-L1 inhibitor atezolizumab (achieved a Partial Response and remained on therapy for 23 months). Following treatment with NUC-3373 plus pembrolizumab, the patient achieved
100% reduction in the target lesion (considered a confirmed Partial Response due to the presence of non-target lesions) and remains on treatment for over 10 months. - 75-year-old patient with BRAF mutant metastatic cutaneous melanoma who had previously received pembrolizumab (best response of Progressive Disease within 5 months) followed by dabrafenib plus trametinib (discontinued trametinib after 1 month due to toxicity and achieved Stable Disease before progressing after seven years on dabrafenib). Following treatment with NUC-3373 plus pembrolizumab, this patient achieved a confirmed Partial Response with an
81% reduction in the target lesion and remains on treatment for over 12 months.
Module 2 included 4 patients with non-small cell lung cancer (NSCLC) or pleural mesothelioma who had disease progression on, or were unable to tolerate, prior chemotherapy-containing regimens. Docetaxel is the current standard of care for NSCLC patients without targetable alterations who progress on PD-(L)1 inhibitor-based therapy, however, it is associated with modest clinical benefit (median PFS of 3-4 months) and substantial toxicity. Following treatment of the first 4 patients in this module, enrollment was put on hold due to toxicity challenges with docetaxel. Despite this, 2 patients achieved prolonged Stable Disease. Protocol modifications to include the use of a different taxane in this combination are currently being considered.
Module 2 Selected Case Studies: NUC-3373 plus docetaxel in patients with lung cancer
- 60-year-old patient with pleural mesothelioma who had previously received carboplatin plus pemetrexed (progressed within 4 months), the PD-1 inhibitor nivolumab (progressed within 4 months), and carboplatin plus pemetrexed (progressed within 1 month). Following treatment with NUC-3373 plus docetaxel, the patient achieved Stable Disease for more than 13 months (ongoing).
- 77-year-old patient with squamous NSCLC who had previously received carboplatin plus paclitaxel plus pembrolizumab (Stable Disease for 2 months) followed by maintenance pembrolizumab (progressed within 21 months). Following treatment with NUC-3373 plus docetaxel, the patient achieved Stable Disease for 7 months.
Full details can be found in the publication: Link
Professor David Harrison, NuCana’s Head of Translational Medicine, stated: “We previously presented data on NUC-3373’s ability to elicit the release of Damage Associated Molecular Patterns (DAMPs), promote an anti-tumor immune response, and potentiate the activity of PD-1 inhibitors in human cancer cell lines. These data led us to investigate the combination of NUC-3373 plus pembrolizumab so we are very excited to observe these encouraging clinical findings in PD-(L)1 inhibitor experienced patients.”
Professor Harrison continued: “We have also demonstrated that NUC-3373 is a very potent thymidylate synthase inhibitor and causes DNA damage, leading us to hypothesize that NUC-3373 may be an attractive alternative to pemetrexed in patients with NSCLC and mesothelioma. Observing that NUC-3373 in combination with docetaxel is stabilizing disease in these hard-to-treat patient populations provides further evidence supporting this hypothesis.”
Hugh S. Griffith, NuCana’s Founder and Chief Executive Officer, said: “We are very excited that these NUC-3373 combinations have been observed to provide a meaningful clinical benefit to patients who had exhausted all other treatment options. We recently presented encouraging efficacy and safety data at ESMO on NUC-7738 plus pembrolizumab in patients with metastatic melanoma who were refractory or resistant to PD-1 inhibitors. We are pleased to have two Phase 2 product candidates in our portfolio, each with a distinct mechanism of action, that can potentiate PD-1 inhibitors in PD-(L)1 resistant patients. We look forward to sharing additional data from the NuTide:303 study and our clinical development plans for both NUC-3373 and NUC-7738 in the near future.”
About NuCana
NuCana is a clinical-stage biopharmaceutical company focused on significantly improving treatment outcomes for patients with cancer by applying our ProTide technology to transform some of the most widely prescribed chemotherapy agents, nucleoside analogs, into more effective and safer medicines. While these conventional agents remain part of the standard of care for the treatment of many solid and hematological tumors, they have significant shortcomings that limit their efficacy and they are often poorly tolerated. Utilizing our proprietary technology, we are developing new medicines, ProTides, designed to overcome the key limitations of nucleoside analogs and generate much higher concentrations of anti-cancer metabolites in cancer cells. NuCana’s pipeline includes NUC-3373 and NUC-7738. NUC-3373 is a new chemical entity derived from the nucleoside analog 5-fluorouracil, a widely used chemotherapy agent. NUC-3373 is currently being evaluated in a Phase 1b/2 modular study (NuTide:303) of NUC-3373 in combination with the PD-1 inhibitor pembrolizumab for patients with advanced solid tumors and in combination with docetaxel for patients with lung cancer. NUC-7738 is a novel anti-cancer agent that disrupts RNA polyadenylation, profoundly impacts gene expression in cancer cells and targets multiple aspects of the tumor microenvironment. NUC-7738 is in the Phase 2 part of a Phase 1/2 study which is evaluating NUC-7738 as a monotherapy in patients with advanced solid tumors and in combination with pembrolizumab in patients with melanoma.
Forward-Looking Statements
This press release may contain “forward-looking” statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are based on the beliefs and assumptions and on information currently available to management of NuCana plc (the “Company”). All statements other than statements of historical fact contained in this press release are forward-looking statements, including statements concerning the Company’s planned and ongoing clinical studies for the Company’s product candidates and the potential advantages of those product candidates, including NUC-3373 and NUC-7738; the initiation, enrollment, timing, progress, release of data from and results of those planned and ongoing clinical studies; the Company’s goals with respect to the development, regulatory pathway and potential use, if approved, of each of its product candidates; and the utility of prior non-clinical and clinical data in determining future clinical results. In some cases, you can identify forward-looking statements by terminology such as “may,” “will,” “should,” “expects,” “plans,” “anticipates,” “believes,” “estimates,” “predicts,” “potential” or “continue” or the negative of these terms or other comparable terminology. Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause the Company’s actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. These risks and uncertainties include, but are not limited to, the risks and uncertainties set forth in the “Risk Factors” section of the Company’s Annual Report on Form 20-F for the year ended December 31, 2023 filed with the Securities and Exchange Commission (“SEC”) on March 20, 2024, and subsequent reports that the Company files with the SEC. Forward-looking statements represent the Company’s beliefs and assumptions only as of the date of this press release. Although the Company believes that the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee future results, levels of activity, performance or achievements. Except as required by law, the Company assumes no obligation to publicly update any forward-looking statements for any reason after the date of this press release to conform any of the forward-looking statements to actual results or to changes in its expectations.
For more information, please contact:
NuCana plc
Hugh S. Griffith
Chief Executive Officer
+44 131-357-1111
info@nucana.com
ICR Westwicke
Chris Brinzey
+1 339-970-2843
chris.brinzey@westwicke.com
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