volrustomig (MEDI5752) / AstraZeneca - LARVOL DELTA

Phase 1b study of first-line (1L) trastuzumab deruxtecan (T-DXd) plus volrustomig in patients (pts) with HER2-overexpressing (HER2-OE) non-small cell lung cancer (NSCLC): DESTINY-Lung03 (DL-03) Part 5 (ELCC 2026) - No abstract available

Clinical • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

Volrustomig, a novel bispecific PD-1/CTLA-4 monoclonal antibody, as single-agent first-line (1L) therapy for unresectable pleural mesothelioma (PM): Substudy 5 of the eVOLVE-02 phase 2 study (ELCC 2026) - No abstract available

Clinical • P2 data • Lung Cancer • Solid Tumor • CTLA4

Casdatifan (Cas) monotherapy in patients (pts) with previously treated clear cell renal cell carcinoma (ccRCC): Safety, efficacy and subgroup analysis across multiple doses from ARC-20, a phase 1 open-label study. (ASCO-GU 2025) - P1 | "In heavily pretreated pts with ccRCC, Cas monotherapy was well tolerated with promising early clinical activity across IMDC risk groups. Cas 100 mg QD will be combined with VEGFR-TKI (cabozantinib) in the phase 3 PEAK-1 trial and immunotherapy (volrustomig) in a separate upcoming first-line trial. aEfficacy-evaluable pts: all pts who had measurable disease at BL, received ≥1 dose and had ≥1 post-BL efficacy assessment, or who discontinued study treatment due to progression or death."

Clinical • IO biomarker • Monotherapy • P1 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • EPAS1 • HIF1A

Study of Volrustomig in Women With High Risk Locally Advanced Cervical Cancer (eVOLVE-Cervical) (clinicaltrials.gov) - P3 | N=800 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Oct 2029 ➔ Sep 2030 | Trial primary completion date: Nov 2026 ➔ Nov 2027

Trial completion date • Trial primary completion date • Cervical Cancer • Oncology • Solid Tumor • PD-L1

MEDI5752 or pembrolizumab (P) plus carboplatin/pemetrexed (CP) in treatment-naïve (1L) non-small cell lung cancer (NSCLC): A phase Ib/II trial (ESMO 2022) - P1 | "Conclusions M1500+C improved DOR, PFS and OS compared to P+C in a randomized signal finding trial in 1L Nsq NSCLC. Emerging data with M750+C shows similarly encouraging efficacy, especially in PD-L1<1% subgroup, with improved tolerability."

Late-breaking abstract • P1/2 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study of Volrustomig in Women With High Risk Locally Advanced Cervical Cancer (IVOLGA) (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Cervical Cancer • Oncology • Solid Tumor • PD-L1

Safety and clinical activity of MEDI5752, a PD-1/CTLA-4 bispecific checkpoint inhibitor, as monotherapy in patients (pts) with advanced renal cell carcinoma (RCC): Preliminary results from an FTIH trial. (ASCO 2022) - P1 | "MEDI5752 monotherapy showed deep and durable antitumor activity in pts with advanced RCC, despite high rates of treatment D/C, particularly in the 1L setting. To better characterize the risk-benefit profile, MEDI5752 is now being explored at doses <1500 mg in 1L ccRCC expansion cohorts."

Checkpoint inhibition • Clinical • Monotherapy • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Hepatology • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor • CTLA4

MEDI5752 (volrustomig), a novel PD-1/CTLA-4 bispecific antibody, in the first-line (1L) treatment of 65 patients (pts) with advanced clear cell renal cell carcinoma (aRCC) (ESMO 2023) - P1, P1b | "Volrustomig with lenvatinib is also being evaluated in 1L aRCC (NCT04522323). Table: 1883MO Efficacy DCO 25Jan2023 M750 M500 Total IMDC Total IMDC F I/P F I/P Response-evaluable, N 32 8 24 33 12 21 ORR, n (%) 15 (46.9) 2 (25) 13 (54.2) 15 (45.5) 7 (58.3) 8 (38.1) CR, n (%) 3 (9.4) 1 (12.5) 2 (8.3) 2 (6.1) 2 (16.7) 0 (0) DCR, n (%) 28 (87.5) 6 (75) 22 (91.7) 23 (69.7) 11 (91.7) 12 (57.1) Progressive disease, n (%) 4 (12.5) – – 8 (24.2) – – mPFS (95% CI), months 11.1 (4.5–NE) – – 9.9 (3.9–NE) – – Per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. CI, confidence interval; CR, complete response; DCR, disease control rate; F, favorable; IMDC, International Metastatic RCC Database Consortium; I/P, intermediate/poor; mPFS, median progression free survival; NE, not estimable."

Clinical • Metastases • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CTLA4 • PD-1

WIRE: Window of Opportunity Clinical Trials Platform for Evaluation of Novel Treatments Strategies in Renal Cell Cancer (KCRS 2024) - P2 | "Cediranib + Olaparib (a PARP inhibitor), 3...Volrustomig (anti PD-1/CTLA4 bispecific) and 5. Rilvegostomig (anti PD-1/TIGIT bispecific)...WIRE may identify novel biomarkers of response and toxicity, to inform treatment selection for patients. The data generated will be a foundation for further trials of these IMPs in advanced disease."

Clinical • IO biomarker • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CD8 • TIGIT

Volrustomig + platinum doublet chemotherapy (CTx) in first-line non-small cell lung cancer (NSCLC): Phase 1b trial update (IASLC-WCLC 2024) - P3 | "Conclusions : Volrustomig 750mg + CTx demonstrates robust PD-1/CTLA-4 blockade, manageable safety, and promising efficacy in 1L advanced NSCLC, especially in patients with PD-L1 TC <1%. The ongoing phase 3 EVOLVE-Lung02 trial (NCT05984277) is evaluating volrustomig + CTx for metastatic NSCLC with PD-L1 TC <50%."

Clinical • IO biomarker • P1 data • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

First-line (1L) trastuzumab deruxtecan (T-DXd) with volrustomig and fluoropyrimidine in patients with HER2-low gastric cancer (GC), gastroesophageal junction adenocarcinoma (GEJA), or esophageal adenocarcinoma (EA): DESTINY-Gastric03 (DG-03) part 5. (ASCO-GI 2026) - P2 | "In Part 2 of DG-03, 1L T-DXd with fluoropyrimidine and/or pembrolizumab demonstrated promising antitumor activity in metastatic HER2+ GC/GEJA/EA... In Part 5, patients with previously untreated HER2-low (IHC 2+/ISH− or IHC 1+) advanced or metastatic GC/GEJA/EA will receive T-DXd with volrustomig and fluoropyrimidine (5-fluorouracil or capecitabine)...The primary endpoint is confirmed objective response rate by investigator assessment per RECIST 1.1. Secondary endpoints include disease control rate, duration of response, and progression-free survival by investigator assessment per RECIST 1.1; overall survival; safety (adverse events and serious adverse events); pharmacokinetics; and immunogenicity."

Clinical • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

Arcus Outlines 2026 Plans for Casdatifan, its Potential Best-in-Class HIF-2a Inhibitor… (Businesswire) - "Casdatifan plus zimberelimab (Arcus’s anti-PD-1 antibody): This combination is currently being evaluated in ARC-20, and this cohort has completed enrollment....Casdatifan plus anti-PD-1-containing regimens: Arcus is planning to initiate new cohorts to evaluate two other TKI-free casdatifan plus anti-PD-1-containing regimens in the 1L setting. Casdatifan plus volrustomig (AstraZeneca’s anti-PD-1/CTLA-4 bispecific antibody): This combination is being evaluated in the eVOLVE-RCC02 study....Data from these cohorts will inform and enable the initiation of a Phase 3 study for a casdatifan-containing, TKI-free regimen in the 1L setting. Arcus is targeting initiation of this study by year-end 2026."

New P3 trial • Trial status • Clear Cell Renal Cell Carcinoma

eVOLVE-Lung02: A Global Study of Volrustomig (MEDI5752) Plus Chemotherapy Versus Pembrolizumab Plus Chemotherapy for Participants With Metastatic Non-small Cell Lung Cancer. (clinicaltrials.gov) - P3 | N=1200 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • PD-L1 • ROS1

Volrustomig co-operatively binds to PD-1 and CTLA-4 and causes PD-1 degradation in tumour antigen specific T cells (ESMO-IO 2025) - "Furthermore, we demonstrated that this MoA has functional consequences regarding antigen specific killing and cytokine release. We have also demonstrated V mediated PD-1 degradation and confirmed this further differentiates V from conventional bivalent monospecific anti-CTLA-4/anti-PD-1 antibodies."

IO biomarker • Oncology • CTLA4 • MLANA • PD-1

Volrustomig drives superior CTLA-4 blockade, induces sustained PD-1 degradation, and enhances T cell function ex vivo (ESMO-IO 2025) - "PBMCs, disaggregated tumor cells (DTCs), or human tumor slice cultures (TSCs) were treated with volrustomig or a co-formulation of a bivalent monospecific anti-PD-1 (clone LO115) and anti-CTLA-4 (tremelimumab) antibodies in the presence or absence of exogenous anti-CD3 stimulation. Ex vivo, volrustomig enhanced TIL functionality as detected by increased IFNγ secretion from non-small cell lung cancer DTCs and gastric TSCs.Conclusions Volrustomig demonstrates cooperative binding, induces sustained PD-1 degradation, and enhances IFNγ secretion in vitro, and ex vivo. These findings support volrustomig's unique mechanistic properties and underscore its differentiation from co-formulations of bivalent monospecific anti-PD-1 and anti-CTLA-4 antibodies."

IO biomarker • Preclinical • Gastric Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • IFNG • NCAM1

The Landscape of Bispecific Antibodies in Solid Tumor Oncology: Trends, Challenges, and Opportunities. (PubMed, Cancer Med) - "Since the first BsAb approval in 2014, the field has rapidly expanded, with solid tumor oncology advancing dynamically. The major focus has been on combining BsAbs with immunotherapy strategies, followed by targeting known oncogenic pathways. The shift toward biotechnology-led innovation underscores the growing therapeutic and financial interest in this field. Optimizing the efficacy and safety of these molecules is key to paving the way for the next era of immune and precision oncology."

Biomarker • IO biomarker • Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ALK • EGFR • HER-2

eVOLVE-RCC02: A Study to Investigate the Efficacy and Safety of Volrustomig ± Casdatifan vs Nivolumab + Ipilimumab as 1L Treatment for Advanced ccRCC (clinicaltrials.gov) - P3 | N=1116 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Monotherapy • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

eVOLVE-Meso: MEDI5752 in Combination With Carboplatin Plus Pemetrexed in Unresectable Pleural Mesothelioma (clinicaltrials.gov) - P3 | N=825 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Mar 2028 ➔ Nov 2028 | Trial primary completion date: Mar 2027 ➔ Nov 2027

Trial completion date • Trial primary completion date • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Pleural Mesothelioma • Solid Tumor

GEMINI-Hepatobiliary: Study of Novel Immunomodulators as Monotherapy and in Combination With Anticancer Agents in Participants With Advanced Hepatobiliary Cancer (clinicaltrials.gov) - P2 | N=294 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Dec 2026 ➔ Oct 2027 | Trial primary completion date: Dec 2025 ➔ Oct 2026

Monotherapy • Trial completion date • Trial primary completion date • Biliary Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Volrustomig: Data from P3 eVOLVE-Meso trial (NCT06097728) for 1L unresectable malignant pleural mesothelioma post 2026 (AstraZeneca) - Q3 2025 Results: Data from P3 eVOLVE-HNSCC trial (NCT06129864) for locally advanced HNSCC post 2026

P3 data • Malignant Pleural Mesothelioma • Oncology • Squamous Cell Carcinoma of Head and Neck

Volrustomig: Data from P3 eVOLVE-Cervical trial (NCT06079671) in patients with high-risk locally advanced cervical cancer post 2026 (AstraZeneca) - Q3 2025 Results: Data from P3 eVOLVE-Lung02 trial (NCT05984277) for 1L metastatic NSCLC with PD-L1 <50% post 2026

P3 data • Cervical Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Volrustomig: Data from P2 eVOLVE-02 trial (NCT06535607) for advanced/metastatic solid tumors in post 2026 (AstraZeneca) - Q3 2025 Results

P2 data • Oncology • Solid Tumor

Volrustomig: Data from P2 CANTOR trial (NCT06792695) for metastatic CRC post 2026 (AstraZeneca) - Q3 2025 Results: Data from P1 trial (NCT03530397) for advanced solid tumors in H1 2026

P1 data • P2 data • Colorectal Cancer • Oncology • Solid Tumor

Development and utilization of a humanized mouse tumor model to dissect the mechanism of action of the monovalent bispecific anti-CTLA-4/PD-1 antibody (volrustomig). (SITC 2025) - "We developed a 25-marker spectral flow cytometry antibody panel to assess major immune cell lineage populations, the amount of T-cell activation and expression levels of immune checkpoint markers. In parallel, bulk RNA sequencing of tumor samples was conducted to characterize the genetic changes associated with the immune response following antibody treatment (figure 1).Results Our in vivo analysis revealed that 1) antigen recognition favors the recruitment of immune cells in tumors and this infiltration is potentiated with volrustomig in comparison with anti-PD-1 monotherapy, 2) high dimensional flow cytometry revealed that volrustomig gives rise to distinct infiltrating T cell subsets but alters myeloid recruitment in tumors and 3) transcriptomic analyses showed a distinct program triggered by volrustomig with significant up-regulation of genes encoding for IFNγ-signaling pathway and a specific set of transcription factors.Conclusions Overall, using in vivo tumor with..."

IO biomarker • Preclinical • Esophageal Cancer • Oncology • Solid Tumor • CD34 • IFNG

Ph1b/2 Study of the Safety and Efficacy of T-DXd Combinations in Advanced HER2-expressing Gastric Cancer (DESTINY-Gastric03) (clinicaltrials.gov) - P2 | N=413 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Jul 2026 ➔ Jun 2027 | Trial primary completion date: Jul 2026 ➔ Jun 2027

Monotherapy • Trial completion date • Trial primary completion date • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Oncology • Solid Tumor • HER-2