volrustomig (MEDI5752) / AstraZeneca - LARVOL DELTA

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

Safety and preliminary activity of MEDI5752, a bispecific anti–PD-1/CTLA-4 antibody, combined with SBRT of one lung metastasis in patients with metastatic STS. (ESMO 2026) - No abstract available

Bispecific • Clinical • Metastases • Oncology

eVOLVE-HNSCC: A global phase 3 study of consolidation volrustomig therapy after definitive concurrent chemoradiotherapy (cCRT) in patients with unresected locally advanced head and neck squamous cell carcinoma (LA-HNSCC) (FHNO 2026) - No abstract available

Clinical • Metastases • P3 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

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

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

Safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy from a first-in-human study of volrustomig, a novel PD-1/CTLA-4 bispecific antibody. (PubMed, Clin Cancer Res) - P1 | "These results support further development of volrustomig as monotherapy and in combination regimens, with phase 3 trials ongoing."

First-in-human • Journal • P1 data • PK/PD data • Dermatology • Endocrine Disorders • Oncology • Pruritus • CTLA4 • PD-1

MEDISARC-SBRT: Study Evaluating the Safety and Efficacy of MEDI5752 in Combination With Stereotactic Radiotherapy in Patients With Metastatic Sarcoma (clinicaltrials.gov) - P1 | N=14 | Completed | Sponsor: Institut Claudius Regaud | Active, not recruiting ➔ Completed | N=20 ➔ 14

Enrollment change • Trial completion • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

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

Dual targets, singular promise: A comprehensive analysis of bispecific antibodies in solid tumor oncology. (ASCO 2025) - "The distribution of clinical molecules also reflects such focus, with dual PD1-CTLA4 inhibitors (Cadonilimab, Volrustomig, Danviostomig) leading the highest number of trials (n=208, 30.5%). Other promising molecules include Ivonescimab (n=51, 7.5%), targeting PD1-VEGF, and Amivantamab-vmjw (n=29, 4.3%), targeting EGFR-MET... 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."

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

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

Volrustomig as Single-Agent First-Line Therapy for Unresectable Pleural Mesothelioma: Substudy 5 of eVOLVE-02 Phase 2 Study (IASLC-WCLC 2026) - P2 | "Nivolumab + ipilimumab and pembrolizumab + pemetrexed + platinum chemotherapy showed improved survival vs chemotherapy alone, with greater benefit in non-epithelioid compared to epithelioid pleural mesothelioma. eVOLVE-02 is recruiting patients; 3 substudies are ongoing in cervical cancer and head and neck squamous cell carcinoma. Substudy 5 enrollment is planned at sites in 8 countries/regions: Australia, Canada, China, Germany, Italy, Taiwan, UK, and USA."

Clinical • P2 data • Cervical Cancer • Epithelioid Pleural Mesothelioma • Head and Neck Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Pleural Mesothelioma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

eVOLVE-01: Volrustomig Priming Regimens Exploratory Phase II Platform Study (clinicaltrials.gov) - P2 | N=194 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Ph1b/2 Study of the Safety and Efficacy of T-DXd Combinations in Advanced HER2-expressing Gastric Cancer (DESTINY-Gastric03) (clinicaltrials.gov) - P2 | N=452 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Monotherapy • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Oncology • Solid Tumor • HER-2

Phase 3 eVOLVE-Lung02 Trial of Volrustomig + Chemotherapy (CT) vs Pembrolizumab + CT in Metastatic NSCLC With PD-L1 TC <50% (IASLC-WCLC 2025) - P1, P3 | "Approximately 1200 patients will be randomized 1:1 to receive histology-specific CT (squamous: paclitaxel plus carboplatin; non-squamous: pemetrexed plus carboplatin + pemetrexed maintenance) in combination with either volrustomig or pembrolizumab 200 mg Q3W for 4 cycles; after this volrustomig (Q3W) or pembrolizumab (200 mg Q3W or 400 mg Q6W where locally approved) will be administered until completion of 24 months of treatment or disease progression, or other discontinuation criteria are met. Key secondary endpoints are PFS and OS in all randomized patients; other secondary endpoints include objective response rate, duration of response, PFS2 (progression after starting first subsequent therapy or death), safety and tolerability, patient-reported outcomes (including NSCLC Symptom Assessment Questionnaire on disease-related symptoms), pharmacokinetics, and immunogenicity. Enrollment is ongoing at approximately 26 sites in 25 countries/regions."

IO biomarker • Metastases • P3 data • Cardiomyopathy • Cardiovascular • CNS Disorders • Congestive Heart Failure • Heart Failure • Hypertension • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Solid Tumor • ALK • BRAF • EGFR • NTRK • PD-L1 • ROS1

First-line rilvegostomig (rilve) plus chemotherapy (CTx) in advanced biliary tract cancer (BTC): Primary analysis of GEMINI-Hepatobiliary substudy 2 Cohort A. (ASCO 2025) - P2 | "GEMINI-Hepatobiliary (NCT05775159) is a phase 2 study evaluating rilve or volrustomig alone or in combination regimens in patients (pts) with advanced hepatocellular carcinoma (substudy 1) or BTC (substudy 2)... Pts aged ≥18 years with previously untreated unresectable/metastatic BTC and an ECOG performance status 0–1 received rilve every 3 weeks (Q3W) for up to 2 years plus gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 on days 1 and 8 Q3W for up to 8 cycles... Rilve plus CTx demonstrated promising efficacy with a manageable safety profile and sustained target engagement. Longer follow-up for data maturity is warranted. Phase 3 studies with rilve in BTC (ARTEMIDE-Biliary 01; DESTINY-BTC01) are ongoing."

Clinical • IO biomarker • Metastases • Biliary Cancer • Biliary Tract Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • PD-L1 • TIGIT

First-line rilvegostomig (rilve) plus chemotherapy (CTx) in advanced biliary tract cancer (BTC): Primary analysis of GEMINI-Hepatobiliary substudy 2 Cohort A (DKK 2026) - P2 | "GEMINI-Hepatobiliary (NCT05775159) is a phase 2 global multi-center study evaluating rilve or volrustomig alone or in combination regimens in patients (pts) with HCC (substudy 1) or BTC (substudy 2)... Pts aged ≥18 years with previously untreated unresectable/metastatic BTC & an ECOG performance status 0–1 received rilve every 3 weeks (Q3W) for up to 2 years plus gemcitabine 1000 mg/m2 & cisplatin 25 mg/m2 on days 1 & 8 Q3W for up to 8 cycles... Rilve plus CTx demonstrated promising efficacy & a manageable safety profile & sustained target engagement. Longer follow-up for data maturity is warranted. Phase 3 studies (ARTEMIDE-Biliary 01; DESTINY-BTC01) are ongoing."

Clinical • IO biomarker • Metastases • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor • PD-L1 • TIGIT

Update on eVOLVE-Lung02 Phase III trial of volrustomig plus chemotherapy in metastatic non-small cell lung cancer (AstraZeneca Press Release) - "AstraZeneca is discontinuing the eVOLVE-Lung02 Phase III trial evaluating volrustomig in combination with chemotherapy as a 1st-line therapy compared to pembrolizumab and chemotherapy in patients with metastatic non-small cell lung cancer...This decision is based on the recommendation of the IDMC...The IDMC concluded that the volrustomig combination was unlikely to meet either of the dual primary endpoints of progression-free survival (PFS) or overall survival (OS) in the primary analysis population of patients with PD-L1 negative tumours (<1%) versus the comparator arm...The safety profile of volrustomig plus chemotherapy was consistent...The other Phase III volrustomig trials continue as planned in cervical cancer, head and neck squamous cell carcinoma and mesothelioma."

DSMB • P3 data • Trial termination • Non Small Cell Lung Cancer

eVOLVE-RCC02: A Study to Investigate the Efficacy and Safety of Volrustomig Casdatifan vs Nivolumab + Ipilimumab as 1L Treatment for Advanced ccRCC (clinicaltrials.gov) - P1 | N=9 | Active, not recruiting | Sponsor: AstraZeneca | Phase classification: P3 ➔ P1 | N=1116 ➔ 9 | Trial completion date: Jul 2032 ➔ Jan 2027 | Trial primary completion date: Feb 2030 ➔ Jan 2027

Enrollment change • Monotherapy • Phase classification • Trial completion date • Trial primary completion date • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

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=895 | Active, not recruiting | Sponsor: AstraZeneca | Trial primary completion date: Apr 2028 ➔ Feb 2029

Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • PD-L1 • ROS1

TROPION-Lung04: Phase 1b Study of Dato-DXd in Combination With Immunotherapy With or Without Carboplatin in Advanced or Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=155 | Active, not recruiting | Sponsor: AstraZeneca | Trial completion date: May 2026 ➔ May 2027

Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • KRAS

Volrustomig: Data from P2 CANTOR trial (NCT06792695) for metastatic CRC in H1 2027 (AstraZeneca) - H1 & Q2 2026 Results: Data from P2 eVOLVE-02 trial (NCT06535607) for advanced/metastatic solid tumors post 2027

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

Volrustomig: Data from P3 eVOLVE-Lung02 trial (NCT05984277) for 1L metastatic NSCLC with PD-L1 <50% in H1 2027 (AstraZeneca) - H1 & Q2 2026 Results: Data from P3 eVOLVE-Meso trial (NCT06097728) for 1L unresectable malignant pleural mesothelioma post 2027

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

Volrustomig: Data from P3 eVOLVE-Cervical trial (NCT06079671) in patients with high-risk locally advanced cervical cancer in H2 2027 (AstraZeneca) - H1 & Q2 2026 Results: Data from P3 eVOLVE-HNSCC trial (NCT06129864) for locally advanced HNSCC post 2027

P3 data • Cervical Cancer • Gynecologic Cancers • Oncology • Squamous Cell Carcinoma of Head and Neck

Volrustomig: Data from P2b eVOLVE-01 trial (NCT06448754) for metastatic NSCLC in H2 2027 (AstraZeneca) - H1 & Q2 2026 Results

P2b data • Lung Cancer • Non Small Cell Lung Cancer • Oncology