rilvegostomig (AZD2936) / AstraZeneca, Compugen, Xoma - LARVOL DELTA

ARTEMIDE-HCC01: A phase III, randomised, open-label, sponsor-blinded, multicentre, global study of rilvegostomig in combination with bevacizumab with or without tremelimumab as first-line (1L) treatment for unresectable hepatocellular carcinoma (uHCC) (ESMO Asia 2025) - P3 | "In the randomisation period, ∼1200 patients will be randomised 1:1:1 to receive tremelimumab, rilvegostomig and bevacizumab (arm A), rilvegostomig and bevacizumab (arm B) or atezolizumab and bevacizumab (arm C) until progression/unacceptable toxicity. Other endpoints include OS (arm B vs arm C), ORR, duration of response, progression-free survival, safety and quality of life. Enrolment began May 2025 and is ongoing."

Clinical • Combination therapy • IO biomarker • P3 data • Hepatocellular Cancer • Oncology • Solid Tumor • AFP • CTLA4 • PD-L1 • TIGIT

ARTEMIDE-HCC01: A phase 3, randomized, open-label, sponsor-blinded, multicentre, global study of rilvegostomig in combination with bevacizumab with or without tremelimumab as first-line (1L) treatment for unresectable hepatocellular carcinoma (uHCC). (ASCO-GI 2026) - P3 | "Funded by AstraZeneca Clinical Trial Registration Number: NCT06921785 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Clinical • Combination therapy • P3 data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

ARTEMIDE-Gastric01: A phase 3 randomized study of rilvegostomig with fluoropyrimidine and trastuzumab deruxtecan (T-DXd) as first-line (1L) treatment for locally advanced or metastatic HER2-positive gastric or gastroesophageal junction cancer (GC/GEJC). (ASCO-GI 2026) - P3 | "Funded by AstraZeneca Clinical Trial Registration Number: NCT06764875 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Clinical • Metastases • P3 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

Real-time monitoring for drug-induced interstitial lung disease with Trastuzumab Deruxtecan and Rilvegostomig combination therapy prevents persistent, symptomatic disease: Safety insights from the I-SPY2.2 platform trial (SABCS 2025) - P2 | "Real-time, centralized monitoring and adjudication allowed for early detection and prompt management of ILD, which both mitigated severity and supported timely therapeutic management. Among the monitoring tools studied, HRCT scanning performed every 6 weeks proved most effective for early ILD identification; PFT and 6MWT did not enhance early detection. This approach offers a potential framework for future studies assessing pulmonary safety in regimens combining agents that have a known risk for inducing ILD."

Clinical • Combination therapy • Breast Cancer

Enhancing AZD5863 (CLDN18.2 T cell engager) activity through combination with chemotherapy and rilvegostomig (PD-1 x TIGIT bispecific) (ESMO-IO 2025) - P1/2 | "Recent clinical success with zolbetuximab has validated CLDN18.2 as a therapeutic target in gastric cancer...Combinatorial activity was assessed with 5-FU/oxaliplatin, gemcitabine/paclitaxel, and rilvegostomig across multiple rounds of AZD5863 treatment...In vivo, combination of AZD5863 with 5-FU and oxaliplatin and a murine surrogate of rilvegostomig resulted in superior tumor growth inhibition, compared with monotherapies.Conclusions AZD5863 induces T cell activation, cytokine secretion, and tumor cell cytotoxicity in vitro, and in vivo. These effects are further potentiated in combination with clinically relevant chemotherapies or rilvegostomig.Legal entity responsible for the study AstraZeneca."

IO biomarker • Gastric Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CLDN18 • PD-1 • TIGIT

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

Randomized, open-label, multicenter, Phase 3 study of trastuzumab deruxtecan (T-DXd) with rilvegostomig vs standard of care (SOC) in first-line, human epidermal growth factor receptor 2 (HER2)-expressing, locally advanced or metastatic (LA/m) biliary tract cancer (BTC): DESTINY-BTC01 (DGHO 2025) - P3 | "A safety run-in will evaluate the safety and tolerability of T-DXd with rilvegostomig, prior to randomization of patients to 3 arms: T-DXd with rilvegostomig; T‑DXd alone; or gemcitabine, cisplatin, and durvalumab. Safety and tolerability will also be assessed. Enrollment is ongoing, with a recruitment target of 620 patients."

Clinical • Metastases • P3 data • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor • HER-2

Potent combination activity of B7-H4 TOP1i ADC puxitatug samrotecan with the monovalent bispecific anti-PD-1/TIGIT antibody rilvegostomig and PARP1 inhibitor saruparib in experimental cancer models (SITC 2025) - "Flow cytometry of the dissociated tumors revealed a greater than 2-fold increase in intratumoral CD3 positive T cells, including a greater than 3-fold increase in cytotoxic effector CD8 positive T cells after triplet therapy compared to untreated mouse tumors. Further, there were decreased intratumoral myeloid derived suppressor cells (MDSCs) and increased macrophages expressing the co-stimulatory molecule CD86 in the triplet therapy group compared to the untreated group.Conclusions Robust anti-tumor activity and tumor immune microenvironment modulation can be achieved with the combination of patuxitug-samrotecan, saruparib and rilvegostomig.Ethics Approval The studies described were approved by the Institutional Animal Care and Use Committee of Astrazeneca under protocol AUP22-25."

Preclinical • Endometrial Cancer • Oncology • Solid Tumor • BIRC5 • CD8 • CD86 • TIGIT • VTCN1

Multimodal profiling reveals unique and overlapping features of rilvegostomig and PD(x) activity in NSCLC tumor explants (SITC 2025) - P1/2 | "These findings underscore rilvegostomig's promise as a novel immuno-oncology agent with activity beyond that of existing immune checkpoint inhibitors.Ethics Approval All work included in this abstract was conducted in accordance with the AstraZeneca Human Biological Sample global standard and approved by the HBS regulatory board. All samples used for these work were collected from patients that have provided informed consent."

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8 • IFNG • TIGIT

Unraveling rilvegostomig's binding characteristics: TIGIT anchoring increases PD-1 saturation through coordinated engagement (SITC 2025) - P1/2 | "This enhanced, selective targeting of TIGIT-expressing cells and simultaneous blockade of both TIGIT and PD-1 on dual-expressing TILs suggests a significant advantage over conventional anti-PD-(L)1 therapeutic strategies. These mechanistic insights support rilvegostomig's observed clinical activity in NSCLC and validate its differentiated mechanism due to its monovalent bispecific format."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • PD-1 • TIGIT

A randomized phase III study of first-line (1L) trastuzumab deruxtecan (T-DXd) with rilvegostomig or pembrolizumab in patients with HER2-expressing, mismatch repair-proficient (pMMR), primary advanced or recurrent endometrial cancer (EC): DESTINY-Endometrial01/GOG-3098/ENGOT-EN24 (ESMO 2025) - "Approximately 600 pts will be randomized (1:1:1) to 3 arms: T-DXd with rilvegostomig, T-DXd with pembrolizumab, or carboplatin/paclitaxel with pembrolizumab. Safety and tolerability, pharmacokinetics, immunogenicity, and patient-reported tolerability will also be assessed. Enrollment began in March 2025."

Clinical • IO biomarker • Metastases • Mismatch repair • P3 data • pMMR • Endometrial Cancer • Oncology • Solid Tumor • HER-2 • PD-L1 • TIGIT

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

ARTEMIDE-Lung04: A phase III, randomised, double-blind, global study of rilvegostomig or pembrolizumab monotherapy as first-line (1L) treatment for patients with metastatic non-small cell lung cancer (mNSCLC) and programmed cell death ligand-1 (PD-L1) expression ≥50% (ESMO 2025) - P3 | "Other endpoints include objective response rate, duration of response and safety. Enrolment started in April 2025 and is ongoing."

Clinical • IO biomarker • Metastases • Monotherapy • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1 • TIGIT

Efficacy and safety of rilvegostomig, an anti-PD-1/TIGIT bispecific antibody, for checkpoint inhibitor (CPI)-naïve metastatic non-small cell lung cancer (mNSCLC): ARTEMIDE-01 (ESMO 2025) - P1/2, P3 | "Data supports ongoing Ph3 studies in mNSCLC including ARTEMIDE-Lung02 (NCT06692738), -Lung03 (NCT06627647) and -Lung04 (NCT06868277). Table: 1853MO PD-L1 TPS (local) 1–49% ≥50% Rilvegostomig 750 mg CPI-naive (n=31) CPI + CT-naïve (n=18) CPI-naïve (n=34) CPI + CT-naïve (n=31) Response, n (%) ORR 9 (29.0) 8 (44.4) 21 (61.8) 21 (67.7) Complete response 0 0 1 (2.9) 1 (3.2) Partial response 9 (29.0) 8 (44.4) 20 (58.8) 20 (64.5) Stable disease 11 (35.5) 5 (27.8) 9 (26.5) 7 (22.6) Progression 9 (29.0) 5 (27.8) 4 (11.8) 3 (9.7) Not evaluable 2 (6.5) 0 0 0 Median (95% CI) DoR, months 9.9 (4.1, 14.6) 8.5 (4.1, NC) NC (10.3, NC) NC (10.3, NC) PFS Events, n (%) 27 (87.1) 15 (83.3) 18 (52.9) 15 (48.4) Median (95% CI) PFS, months 6.1 (2.7, 8.3) 7.8 (1.9, 12.5) 12.3 (8.4, NC) 21.2 (10.2, NC) PFS-12, % (95% CI) 27.2 (12.9, 43.6) 30.1 (11.1, 52.0) 55.5 (37.3, 70.3) 60.8 (41.4, 75.6)"

Checkpoint inhibition • Clinical • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-1 • TIGIT

AstraZeneca advances its ambition to redefine cancer care with new data across its diverse, industry-leading portfolio and pipeline at the European Society for Medical Oncology (ESMO) Congress, October 17-21, 2025. (AstraZeneca Press Release)

Clinical data • Platinum resistant • pMMR • Tumor mutational burden • Castration-Resistant Prostate Cancer • Cholangiocarcinoma • Colorectal Cancer • Endometrial Cancer • Gastric Cancer • Hormone Sensitive Prostate Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Triple Negative Breast Cancer

Datopotamab deruxtecan (Dato-DXd) + rilvegostomig (rilve) in patients (pts) with locally advanced or metastatic urothelial cancer (a/mUC): Results from the phase II TROPION-PanTumor03 study (ESMO 2025) - P2 | "We present results from pts with a/mUC who received Dato-DXd + rilve, an Fc reduced anti–PD-1/TIGIT bispecific antibody (anti–TIGIT component derived from COM902 [Compugen]). Methods Pts with histologically documented unresectable a/mUC were enrolled in two eligible populations: 1L population, no prior systemic therapy in the a/mUC setting (progression >12 months after platinum-based neoadjuvant or adjuvant therapy permitted), and ineligible for cisplatin-based chemotherapy (CT); 2L population, had received previous platinum-based CT in the a/mUC setting or progressed <12 months after platinum-based neoadjuvant or adjuvant therapy...Conclusions Dato-DXd in combination with rilve showed encouraging efficacy and a manageable safety profile in pts with a/mUC. Table: 3072MO Incidence of AEs, n (%) Dato-DXd + rilve 1L (n=22) 2L (n=18) TRAEs 21 (95.5) 17 (94.4) Grade ≥3 TRAEs 4 (18.2) 7 (38.9) Any TRAE leading to: Dose reduction of any study treatment 12 (54.5) 4..."

Clinical • Metastases • P2 data • Pan tumor • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • TIGIT

AB02: A Study of Rilvegostomig or Durvalumab Plus Chemotherapy for First-Line Treatment of Biliary Tract Cancer (ARTEMIDE-Biliary02) (clinicaltrials.gov) - P3 | N=1100 | Not yet recruiting | Sponsor: AstraZeneca

New P3 trial • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor • PD-L1

A Study to Investigate Safety of AZD6750 in Adult Participants With Select Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=60 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Apr 2029 ➔ Oct 2029 | Trial primary completion date: Apr 2029 ➔ Oct 2029

Trial completion date • Trial primary completion date • Breast Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Genito-urinary Cancer • Head and Neck Cancer • High Grade Serous Ovarian Cancer • Lung Cancer • Melanoma • Merkel Cell Carcinoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

BLUESTAR: A Phase I/IIa Study of AZD8205 Given Alone or in Combination With Anticancer Drugs, in Participants With Advanced or Metastatic Solid Malignancies (clinicaltrials.gov) - P1/2 | N=370 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Mar 2027 ➔ Sep 2027 | Trial primary completion date: Mar 2027 ➔ Sep 2027

Monotherapy • Trial completion date • Trial primary completion date • Biliary Cancer • Biliary Tract Cancer • Breast Cancer • Endometrial Cancer • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor

LIBRA: A Study of Novel Combinations in Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P2 | N=278 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting | Trial primary completion date: Sep 2026 ➔ Mar 2027

Enrollment open • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

ARTEMIDE-Lung02: A Phase 3 Global Study of Rilvegostomig or Pembrolizumab Plus Chemotherapy for 1L Metastatic Squamous NSCLC (IASLC-WCLC 2025) - P3 | "Methods : Approximately 880 pts will be randomised 1:1 to either Arm A: rilvegostomig + chemotherapy (carboplatin + paclitaxel or nab-paclitaxel) intravenous (IV) every three weeks (Q3W) for 4 cycles followed by rilvegostomig IV Q3W, or Arm B: pembrolizumab + chemotherapy IV Q3W for 4 cycles followed by pembrolizumab IV Q3W. Additional endpoints include safety/tolerability and biomarkers. Enrolment is planned across approximately 350 sites in 25-30 countries."

Clinical • IO biomarker • Metastases • P3 data • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Solid Tumor • TIGIT

TROPION-Lung12: A phase 3 study of adjuvant datopotamab deruxtecan and rilvegostomig in ctDNA-positive or high-risk pathology stage I NSCLC. (PubMed, J Thorac Cardiovasc Surg) - P3 | "Patients will be randomized 2:1:2 to receive Dato-DXd (6 mg/kg IV Q3W) plus rilvegostomig (750 mg IV Q3W) for 4 cycles followed by rilvegostomig (up to 12 months/18 cycles total); rilvegostomig alone (up to 12 months/18 cycles total); or standard of care (SoC) for up to 12 months. The primary endpoint is disease-free survival assessed using blinded independent central review per RECIST v1.1, with key secondary endpoints including overall survival, for Dato-DXd plus rilvegostomig vs SoC arms."

Circulating tumor DNA • IO biomarker • Journal • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • TIGIT

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=165 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting | N=371 ➔ 165 | Trial completion date: Jan 2026 ➔ Apr 2026 | Trial primary completion date: Jan 2026 ➔ Apr 2026

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • PD-L1

Rilvegostomig Enhances Ex Vivo Immune Activation in Patient-Resected NSCLC Tumors Over PDx or PDX/aTIGIT Combination Therapy (IASLC-WCLC 2025) - P1/2, P3 | "Additionally, rilvegostomig's Fc-reduced design prevents the depletion of PD-1+/TIGIT+ effector cells required for an optimal anti-tumor response. Ongoing analyses are dissecting the mechanisms driving the enhanced activity of rilvegostomig."

Combination therapy • IO biomarker • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8 • IFNG • TIGIT

DESTINY-Lung03: Phase Ib Study of the Safety of T-DXd and Immunotherapy Agents With and Without Chemotherapy in Advanced or Metastatic HER2+, Non-squamous NSCLC (clinicaltrials.gov) - P1 | N=244 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Dec 2025 ➔ Jun 2027 | Trial primary completion date: Dec 2025 ➔ Jun 2027

IO biomarker • Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor