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The company highlighted that these findings bolster the understanding of NUC-7738’s mechanism of action, aligning with results from the ongoing Phase 1/2 NuTide:701 study. This study has shown a favorable safety profile, significant tumor volume reduction, and extended progression-free survival (PFS) in metastatic melanoma patients who have become refractory to PD-1 inhibitors. Building on this positive momentum, regulators have greenlit an expansion of the study to enroll an additional 28 patients. NuCana is gearing up for a meeting with the U.S. FDA to discuss a potential registration strategy for NUC-7738.
La società ha dichiarato che questi risultati rafforzano il meccanismo d’azione di NUC-7738 e sono in linea con i risultati dello studio in corso di Phase 1/2 NuTide:701, che, secondo quanto riferito dall’azienda, ha mostrato un profilo di sicurezza favorevole, una significativa riduzione del volume tumorale e una prolungata sopravvivenza libera da progressione nel melanoma metastatico refrattario agli inibitori PD-1. Le autorità hanno approvato un’espansione per reclutare altri 28 pazienti, e NuCana prevede un incontro con la FDA degli Stati Uniti per discutere una strategia di registrazione.
La empresa dijo que estos hallazgos fortalecen el mecanismo de acción de NUC-7738 y se alinean con los resultados del estudio Fase 1/2 NuTide:701 en curso, que la compañía informa que ha mostrado un perfil de seguridad favorable, una reducción significativa del volumen tumoral y una supervivencia libre de progresión prolongada en melanoma metastásico refractario a inhibidores de PD-1. Las autoridades aprobaron una expansión para reclutar a otros 28 pacientes, y NuCana planea una reunión con la FDA de los EE. UU. para discutir una estrategia de registro.
회사는 이러한 결과가 NUC-7738의 작용 기전을 강화하고 진행 중인 1상/2상 NuTide:701 연구의 결과와 일치한다고 밝혔으며, 이 연구는 PD-1 억제제 저항성 전이성 흑색종에서 안전성 프로필이 우수하고 종양 부피 감소가 의미 있으며 무진행생존 기간이 증가했다고 보고합니다. 규제 당국은 추가로 28명의 환자를 모집하기 위한 확장을 승인했고, NuCana는 등록 전략을 논의하기 위해 미국 FDA와의 회의를 계획하고 있습니다.
La société a déclaré que ces résultats renforcent le mécanisme d’action de NUC-7738 et s’alignent sur les résultats de l’essai en cours de Phase 1/2 NuTide:701, qui, selon la société, a montré un profil de sécurité favorable, une réduction significative du volume tumoral et une survie sans progression prolongée chez le mélanome metastatique réfractaire aux inhibiteurs PD-1. Les autorités ont approuvé une extension pour recruter un complément de 28 patients, et NuCana prévoit une réunion avec la FDA des États-Unis pour discuter d’une stratégie d’enregistrement.
Das Unternehmen sagte, dass diese Ergebnisse den Wirkmechanismus von NUC-7738 untermauern und mit den Ergebnissen der laufenden Phase-1/2 NuTide:701-Studie übereinstimmen, die laut dem Unternehmen ein günstiges Sicherheitsprofil, eine signifikante Reduktion des Tumorvolumens und eine verlängerte progressionsfreie Überleben bei PD-1-Inhibitor-refraktären metastatischen Melanomen gezeigt hat. Regulierungsbehörden genehmigten eine Erweiterung zur Rekrutierung weiterer 28 Patienten, und NuCana plant eine Sitzung mit der US-FDA, um eine Registrierungsstrategie zu besprechen.
قالت الشركة إن هذه النتائج تعزز آلية عمل NUC-7738 وتتماشى مع نتائج الدراسة المرحلة 1/2 NuTide:701 الجارية، التي تفيد الشركة بأنها أظهرت ملف سلامة مناسب، تقليصاً ملحوظاً في حجم الورم ومدة بقاء دون تقدم في ميلانوما متقدم مقاوم لمثبطات PD-1. وافقت الجهات التنظيمية على توسيع لإشراك 28 مريضاً إضافياً، وتخطّط NuCana لعقد اجتماع مع FDA الأمريكية لمناقشة استراتيجية التسجيل.
公司表示，这些发现强化了 NUC-7738 的作用机制，并与进行中的 1/2 期 NuTide:701 研究结果一致，该研究据称显示出有利的安全性特征、显著的肿瘤体积缩小以及在对 PD-1 抑制剂耐药的转移性黑色素瘤中延长的无进展生存期。监管机构已批准扩展招募额外的 28 名患者，NuCana 计划与美国 FDA 就注册策略举行会议。
Positive
- Preclinical synergy observed in 10 patient-derived RCC organoids
- NuTide:701 reports favorable safety profile
- NuTide:701 reports meaningful tumor volume reduction
- Regulatory approval to expand NuTide:701 by 28 patients
- Planned meeting with the U.S. FDA to discuss registration
Negative
- Organoid data derived from a small cohort of 10 patients
- NuTide:701 is an early-stage Phase 1/2 study without randomized data
- Reported clinical effects lack published quantitative endpoints in this release
Insights
PDO and autologous TIL co-culture data show NUC-7738 enhances PD-1 inhibitor tumor killing in RCC models, supporting observed clinical signals.
NUC-7738 demonstrates mechanistic synergy with PD-1 blockade in ten patient-derived renal cell carcinoma organoids co-cultured with autologous tumor-infiltrating lymphocytes, indicating the drug alters cancer cell gene expression via disruption of RNA polyadenylation and increases immune-mediated tumor cell death. The experimental design uses real patient material, which strengthens biological relevance compared with cell lines; however, organoid systems remain models and do not prove clinical benefit on their own.
Key dependencies and risks include translation from organoid/TIL responses to whole-patient immune dynamics and variability across tumor types; findings are encouraging but preclinical. Concrete near-term items to watch are the published poster at ESMO on October 19, 2025 and whether mechanistic biomarkers from the PDO work correlate with responses reported in the ongoing NuTide:701 study over the next 6–18 months.
Clinical expansion and planned FDA discussion follow supportive translational and early clinical signals, raising development momentum.
Regulators approved a 28-patient expansion of the Phase 1/2 NuTide:701 study in PD-1 inhibitor–resistant melanoma, reflecting sufficient safety and signal to merit broader enrollment; the company also plans a meeting with the FDA to discuss registration strategy. These steps materially advance the program from exploratory to deliberate development planning.
Risks include that expansion size and FDA discussions reflect early-phase promise, not confirmatory efficacy; monitor enrollment progress, safety data readouts from the expansion cohort, and the outcome/timing of the FDA meeting as near-term milestones within 2025–2026. The poster at ESMO on October 19, 2025 and subsequent clinical data releases will be the most informative signals for next regulatory decisions.
10/18/2025 – 08:00 AM
NUC-7738 Synergizes with PD-1 Inhibitors to Promote Cancer Cell Death
Data Reinforces Mechanism of Action along with Efficacy and Safety Profile of NUC-7738
BERLIN – NuCana plc (NASDAQ: NCNA) is generating buzz at the European Society for Medical Oncology (ESMO) Congress, where the company presented encouraging data on its investigational drug NUC-7738. The findings suggest a potent synergistic effect when NUC-7738 is combined with PD-1 inhibitors, potentially broadening treatment options for patients with advanced cancers, particularly those who have developed resistance to existing immunotherapies.
The core of NuCana’s presentation focused on a novel model system employing patient-derived organoids (PDOs) from ten individuals diagnosed with renal cell carcinoma (RCC). These PDOs, co-cultured with the patients’ own tumor-infiltrating lymphocytes (TILs), provided a unique platform to observe the drug’s impact in a setting closely mimicking the tumor microenvironment. The results clearly showed enhanced tumor cell eradication when NUC-7738 was combined with PD-1 inhibitors, pointing toward a powerful combinatorial therapeutic strategy.
Digging into the mechanism, the data suggests NUC-7738 disrupts RNA polyadenylation, profoundly impacting gene expression within cancer cells and affecting multiple facets of the tumor’s microenvironment. This multifaceted approach could not only directly target cancer cells but also sensitize them to the effects of PD-1 inhibition, offering a dual-pronged attack against the disease.
These pre-clinical findings are corroborated by early data from the ongoing Phase 1/2 NuTide:701 clinical study evaluating NUC-7738 in patients with advanced solid tumors, including those with metastatic melanoma resistant or refractory to PD-1 inhibitors. This trial has demonstrated a manageable safety profile, alongside significant tumor volume reduction and prolonged progression-free survival in some patients, further validating the potential of NUC-7738. The observed synergy hinges on NUC-7738’s ability to overcome resistance mechanisms developed by tumors against PD-1 inhibitors, a significant hurdle in cancer immunotherapy.
Based on these promising results, regulators have approved an expansion of the NuTide:701 study, paving the way for enrollment of an additional 28 patients with PD-1 inhibitor-resistant melanoma. NuCana intends to leverage these findings in discussions with the U.S. Food and Drug Administration (FDA), aiming to define an optimal registration strategy that could expedite the path to market for NUC-7738.
NuCana’s presentation at ESMO, officially titled: Patient Derived Organoids Reveal Synergy Between NUC-7738 and PD-1 Inhibition in Renal Cell Cancer, with poster presented by H. Abdullah on October 19, highlights a pivotal moment in the company’s clinical development, showing promise against advanced and resistant renal cell cancers.
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-7738 and NUC-3373. 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 (NuTide:701) which is evaluating NUC-7738 as a monotherapy in patients with advanced solid tumors and in combination with pembrolizumab in patients with melanoma. NUC-3373 is a new chemical entity derived from the nucleoside analog 5-fluorouracil, a widely used chemotherapy agent. NUC-3373 is 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.
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 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-7738 and NUC-3373; 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, our ability to raise additional capital sufficient to fund our planned operations and 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, 2024 filed with the Securities and Exchange Commission (“SEC”) on March 20, 2025, 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
Andrew Kay
Executive Chairman
+44 131-357-1111
[email protected]
ICR Healthcare
Chris Brinzey
+1 339-970-2843
[email protected]
FAQ
What did NuCana announce about NUC-7738 and PD-1 inhibitors at ESMO 2025 (NCNA)?
NuCana presented data showing NUC-7738 synergizes with PD-1 inhibitors in patient-derived organoids from 10 RCC patients, increasing tumor cell killing.
How does the ESMO 2025 data relate to the NuTide:701 study for NCNA?
The company said the organoid data reinforce NUC-7738’s mechanism and are consistent with NuTide:701 findings of a favorable safety profile, tumor volume reduction, and prolonged PFS in PD-1 refractory melanoma.
What clinical trial expansion did NuCana announce for NCNA on October 18, 2025?
Regulators approved an expansion of NuTide:701 to recruit an additional 28 patients with PD-1 inhibitor–resistant melanoma.
Will NuCana engage the FDA about NUC-7738 (NCNA) and what for?
NuCana plans to meet with the U.S. FDA to discuss NuTide:701 data and determine an optimal registration strategy to support marketing approval.
How many patient-derived organoids were used to test NUC-7738 plus PD-1 inhibitors?
Co-culture experiments used PDOs derived from 10 renal cell carcinoma patients alongside autologous TILs.
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