NUC-7738 / NuCana - LARVOL DELTA

NuCana Presents Latest Data Demonstrating Clinical Activity and Favorable Safety for NUC-7738 in Patients with PD-1-Resistant Melanoma (GlobeNewswire) - "The data from patients with PD-1 inhibitor-resistant metastatic melanoma treated with NUC-7738 in combination with pembrolizumab continue to demonstrate clinical activity and a favorable safety profile. All patients had progressive disease prior to starting treatment. Clinical activity includes two partial responses (one confirmed) and seven cases of stable disease, notably including one ongoing stable disease converting to a complete metabolic response with no detectable active disease...As of the most recent analysis, nine patients have been treated in the Expansion Cohort, which is part of the planned enrollment of up to 28 additional patients. Combined with the 12 patients previously treated in the Dose Confirmation Cohort, this will provide a total combination dataset comprising up to 40 patients."

P2 data • Trial status • Cutaneous Melanoma • Melanoma

A phase II expansion study of NUC-7738 in combination with pembrolizumab in patients with PD-1 inhibitor-resistant cutaneous melanoma (NuTide:701) (ESMO-IO 2025) - P1/2 | "Patients with measurable disease and ECOG performance status 0-1 who progressed on a prior PD-1 inhibitor are eligible. Patients will receive 1125 mg/m2 NUC7738 Q1W + 200 mg pembrolizumab Q3W and will be evaluated for safety and anti-cancer endpoints, including PFS, BOR, ORR, DOR and DCR using iRECIST and RECIST criteria.Clinical trial identification NCT03829254.Legal entity responsible for the study NuCana."

Clinical • Combination therapy • P2 data • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor

NuCana Announces Grant of Composition-of-Matter Patent for NUC-7738 in China (GlobeNewswire) - "This patent (ZL 202010794701.2) is expected to serve as a key component of the patent protection for NUC-7738, which currently consists of over 85 issued patents worldwide. The composition of matter patent covers the chemical structure of NUC-7738, NuCana’s novel anti-cancer agent currently being evaluated in a Phase 1/2 clinical study (NuTide:701) in combination with pembrolizumab for patients with PD-1 inhibitor refractory or resistant melanoma."

Patent • Melanoma

Patient derived organoids reveal synergy between NUC-7738 and PD-1 inhibition in renal cell carcer (ESMO 2025) - "NUC-7738 combined with pembrolizumab or nivolumab demonstrated synergy, with the NUC-7738–nivolumab combination achieving 5–34% greater tumor cell kill compared to unstimulated TILs alone, as confirmed by over 150 hours of imaging. In addition, it may enable personalised immunotherapy testing. Legal entity responsible for the study University of St Andrews."

Clinical • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Melanoma • Oncology • ANXA5

NuCana Presents Encouraging Data on NUC-7738 in Combination with PD-1 Inhibitors using Primary Patient-Derived Organoids and Autologous Tumor-Infiltrating Lymphocytes at the ESMO Congress 2025 (GlobeNewswire) - "Using patient-derived organoids ('PDOs') from ten patients with RCC and autologous tumor-infiltrating lymphocytes ('TILs'), co-culture experiments reveal that NUC-7738 enhances the effectiveness of PD-1 inhibitors, resulting in increased tumor cell killing....Data to date from NuTide:701 have demonstrated a favorable safety profile, meaningful tumor volume reduction, and prolonged progression-free survival in patients with PD-1 inhibitor refractory and resistant metastatic melanoma."

P1/2 data • Melanoma • Renal Cell Carcinoma

NuCana to Present Data on NUC-7738’s Synergy with PD-1 Inhibitors at the ESMO Congress 2025 (GlobeNewswire)

Clinical data • Renal Cell Carcinoma

NuCana...Provides Business Update (GlobeNewswire) - "First Patients Dosed on Expansion Study of NUC-7738 in Combination with Pembrolizumab for Patients with PD-1 Inhibitor-Resistant Melanoma."

Trial status • Melanoma

Anticipated Milestones: NUC-7738 (GlobeNewswire) - "(i) Announce initial data from the Phase 1/2 expansion study (NuTide:701) of NUC-7738 in combination with pembrolizumab in 2025; (ii) Obtain regulatory guidance from the U.S. Food and Drug Administration on pivotal study design for NUC-7738 in melanoma in 2026; and (iii) Announce final data from the Phase 1/2 expansion study (NuTide:701) of NUC-7738 in combination with pembrolizumab in 2026."

FDA event • P1/2 data • Lymphoma • Melanoma • Solid Tumor

NuCana Reports Fourth Quarter and Year-End 2024 Financial Results and Provides Business Update (GlobeNewswire) - "2025 Anticipated Milestones - NUC-7738: Initiate an expansion of the Phase 1/2 study (NuTide:701) of NUC-7738 in combination with pembrolizumab in patients with melanoma; Announce data from the Phase 1/2 expansion study (NuTide:701) of NUC-7738 in combination with pembrolizumab; and Obtain regulatory guidance from the U.S. Food and Drug Administration on pivotal study design for NUC-7738 in melanoma. NUC-3373: Announce data from the Phase 1b/2 modular study (NuTide:303) of NUC-3373 in combination with pembrolizumab in patients with solid tumors."

FDA event • P1/2 data • Trial status • Colorectal Cancer • Endometrial Cancer • Gastroesophageal Cancer • Melanoma • Microsatellite Instability • Non Small Cell Lung Cancer • Pleural Mesothelioma • Renal Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

NUC7738 Induces Apoptosis Through Modulating Stability of P53 in Esophageal Cancer Cells. (PubMed, J Biochem Mol Toxicol) - "NUC7738, a cordycepin derivative, has shown promise in overcoming the limited in vivo efficacy of its parent compound. Additionally, NUC7738 combined with cisplatin showed enhanced anticancer effects both in vitro and in vivo. These findings highlight greater potential of NUC7738 for clinical application, particularly in improving p53 stability and augmenting chemotherapeutic efficacy."

Journal • Esophageal Cancer • Oncology • Targeted Protein Degradation

NuCana Reports Third Quarter 2024 Financial Results and Provides Business Update (GlobeNewswire) - "2025 Anticipated Milestones - NUC-7738: Initiate an expansion of the Phase 1/2 study (NuTide:701) of NUC-7738 in combination with pembrolizumab in patients with melanoma; Announce data from the Phase 1/2 expansion study (NuTide:701) of NUC-7738 in combination with pembrolizumab; and Obtain regulatory guidance from the U.S. Food and Drug Administration on pivotal study design for NUC-7738 in melanoma. NUC-3373: Initiate an expansion of the Phase 1b/2 modular study (NuTide:303) of NUC-3373 in combination with pembrolizumab in patients with solid tumors; and Announce data from the Phase 1b/2 modular study (NuTide:303) of NUC-3373 in combination with pembrolizumab in patients with solid tumors."

P1/2 data • Trial status • Melanoma • Solid Tumor

NuTide:701: A Safety, Pharmacokinetic and Clinical Activity Study of NUC-7738 in Patients With Advanced Solid Tumours and Lymphoma (clinicaltrials.gov) - P1/2 | N=135 | Recruiting | Sponsor: NuCana plc | N=94 ➔ 135 | Trial completion date: Jun 2024 ➔ Aug 2026 | Trial primary completion date: Jun 2024 ➔ Aug 2026

Enrollment change • Trial completion date • Trial primary completion date • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Melanoma • Oncology • Solid Tumor

Final results of phase I/II study of NUC-7738 as monotherapy and in combination with pembrolizumab: Anti-tumor immune response in PD-1 inhibitor-resistant patients (ESMO 2024) - P1/2 | "NUC-7738 has a favorable safety profile with promising anti-tumor activity as monotherapy and in combination with pembrolizumab. By disrupting RNA polyadenylation, NUC-7738 alters mRNA half-life and expression of immune regulatory proteins, leading to anti-tumor immune response in patients with PD-1 resistance."

Clinical • Combination therapy • IO biomarker • Monotherapy • P1/2 data • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor

NuCana Announces Grant of Composition-of-Matter Patent for NUC-7738 in the United States (GlobeNewswire) - "NuCana plc...announced the issuance of a new patent by the United States Patent and Trademark Office (USPTO) covering NUC-7738’s composition of matter. This patent (US12,054,510) is expected to serve as a key component of the intellectual property protection for NUC-7738, which currently consists of over 80 issued patents worldwide. NUC-7738 is a novel anti-cancer agent currently in a Phase 2 clinical study in combination with pembrolizumab in PD-1 inhibitor resistant melanoma patients..."

Patent • Melanoma

NuCana Presents Encouraging Data on NUC-7738 in Combination with Pembrolizumab in PD-1 Inhibitor Refractory and Resistant Melanoma Patients at the ESMO Congress 2024 (GlobeNewswire) - P1/2 | N=357 | NCT03829254 | Sponsor: NuCana plc | "NuCana plc...presented final data from the Phase 2 NuTide:701 study at the ESMO Congress on NUC-7738 in combination with pembrolizumab for patients with metastatic melanoma who were refractory to or had relapsed on prior PD-1 inhibitor therapy. In this cohort of 12 patients, most of whom had received at least two prior lines of PD-1 inhibitor therapy, nine (75%) achieved disease control, including two patients who achieved Partial Responses.... In addition to achieving these encouraging efficacy signals, the combination of NUC-7738 and pembrolizumab had a favorable safety profile....We look forward to sharing our development plans for NUC-7738 in the near future.'"

P2 data • Melanoma

NuCana Announces Update for Phase 2 Randomized Colorectal Cancer Study (NuCana Press Release) - "NuCana plc...announced that the NuTide:323 study is being discontinued following a pre-planned initial analysis and recommendation from the NuTide:323 Study Steering Committee. While there were prognostic imbalances favoring the control arm, the Steering Committee believed that the combination of NUC-3373 with leucovorin, irinotecan and bevacizumab (NUFIRI+bev) was unlikely to achieve the study’s primary objective of superior Progression Free Survival (PFS) compared to the control arm of 5-FU, leucovorin, irinotecan and bevacizumab (FOLFIRI+bev) in the final analysis....'We look forward to sharing the latest data from the Phase 2 part of the NuTide:701 study of NUC-7738 in combination with pembrolizumab in patients with melanoma at the ESMO annual conference in September 2024'."

P2 data • Trial termination • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

NUC7738 INDUCES APOPTOSIS THROUGH MODULATING STABILITY OF P53 IN ESOPHAGEAL CANCER CELLS (DDW 2024) - "The same results were observed in vivo. Thus NUC7738 may have greater clinical potential than cordycepin."

Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Oncology

NuCana Reports First Quarter 2024 Financial Results and Provides Business Update (GlobeNewswire) - "NUC-7738 (a ProTide transformation of 3’-deoxyadenosine): In 2024, NuCana expects to: Announce data from the Phase 2 part of the Phase 1/2 study (NuTide:701) of NUC-7738 in combination with pembrolizumab in patients with melanoma."

P2 data • Melanoma

RNA regulatory disruption by 3'-dATP: A novel approach to inhibit ribosome biogenesis in cancer (AACR 2024) - P1/2 | "NUC-7738 is currently being investigated in combination with pembrolizumab in patients with advanced melanoma in the Phase 2 part of the clinical study (NCT03829254). Through the development of a novel bioinformatic pipeline we have been able to demonstrate that NUC-7738 disrupts RNA regulation, leading to perturbed RiBi. Targeting RiBi provides a promising approach to treating cancers"

Kidney Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor • RPS3 • RPS6 • SNHG3

Exposing the heterogeneity of the lipidome in the TME of cutaneous melanoma following treatment with NUC-7738 in combination with anti-PD-1 therapy (AACR 2024) - P1/2 | "In combination with anti-PD-1 agent pembrolizumab, NUC-7738 (3'-deoxyadenosine [3'-dA] which is phosphorylated and protected with a phosphoramidate moiety attached at the 5'-position) has shown promising activity in anti-PD-1 refractory melanoma (Phase 2; NCT03829254). This platform provides a powerful investigative tool to simultaneously explore the myriad of factors in the TME that contribute to tumorigenesis and therapeutic response. Further analyses of the role of the lipidome in the TME and intra-tumoral heterogeneity will be explored in paired biopsies from patients with PD-1 inhibitor refractory melanoma."

Combination therapy • Heterogeneity • IO biomarker • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • ASAH1 • CD20 • CD8

NuTide:701: A Safety, Pharmacokinetic and Clinical Activity Study of NUC-7738 in Patients With Advanced Solid Tumours and Lymphoma (clinicaltrials.gov) - P1/2 | N=94 | Recruiting | Sponsor: NuCana plc | Trial completion date: Jan 2024 ➔ Jun 2024 | Trial primary completion date: Jan 2024 ➔ Jun 2024

Metastases • Trial completion date • Trial primary completion date • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Melanoma • Oncology • Solid Tumor

NuCana Reports Third Quarter 2023 Financial Results and Provides Business Update (Yahoo Finance) - "2024 Anticipated Milestones...Announce data from the randomized Phase 2 (NuTide:323) study of NUFIRI-bev compared to the standard of care FOLFIRI-bev for the second-line treatment of patients with colorectal cancer; Announce data from the Phase 2 (NuTide:302) study of NUC-3373 in combination with irinotecan, leucovorin and bevacizumab (NUFIRI-bev) and in combination with oxaliplatin, leucovorin and bevacizumab (NUFOX-bev) for the second-line treatment of patients with colorectal cancer; and Announce data from the Phase 1b (NuTide:303) modular study of NUC-3373 in combination with pembrolizumab in patients with solid tumors and in combination with docetaxel in patients with lung cancer to identify additional indications for development....Announce data from the Phase 2 part of the NuTide:701 study of NUC-7738 in combination with pembrolizumab in patients with melanoma."

P1 data • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Melanoma • Oncology • Skin Cancer • Solid Tumor

NuCana Presents Promising Data on NUC-7738 at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics 2023 (GlobeNewswire) - P1/2 | N=94 | NCT03829254 | Sponsor: NuCana plc | "NuCana plc...announced a presentation on the ongoing NuTide:701 study of NUC-7738 at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics 2023 that took place October 11-15, 2023 in Boston, Massachusetts....In the combination cohort of melanoma patients...numerous patients achieved tumor volume reductions and prolonged time on treatment. One patient who was refractory to the anti-PD-1 plus anti-CTLA-4 therapy combination of nivolumab plus ipilimumab achieved a 50% reduction in tumor volume on NUC-7738 plus pembrolizumab and remains on treatment....Patient tumor biopsy data showed that, following treatment with NUC-7738 plus pembrolizumab, expression of PD-1 was reduced and CD8+ T-cells increased, indicating that NUC-7738 may have the ability to potentiate immunotherapy."

P1/2 data • Melanoma • Oncology • Skin Cancer • Solid Tumor

NuTide:701: A Safety, Pharmacokinetic and Clinical Activity Study of NUC-7738 in Patients With Advanced Solid Tumours and Lymphoma (clinicaltrials.gov) - P1/2 | N=94 | Recruiting | Sponsor: NuCana plc | Trial completion date: Sep 2023 ➔ Jan 2024 | Trial primary completion date: Sep 2023 ➔ Jan 2024

Metastases • Trial completion date • Trial primary completion date • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Melanoma • Oncology • Solid Tumor

NUC-7738 in combination with pembrolizumab in patients with metastatic melanoma: Phase 2 results from the NuTide:701 study. (AACR-NCI-EORTC 2023) - No abstract available

Clinical • Combination therapy • Metastases • P2 data • Melanoma • Oncology • Solid Tumor