puxitatug samrotecan (AZD8205) / AstraZeneca - LARVOL DELTA

TRIAL IN PROGRESS: BLUESTAR-ENDOMETRIAL01 (BE01)/GOG-3110/ENGOT-EN28, A GLOBAL PHASE 3 RANDOMIZED TRIAL OF PUXITATUG SAMROTECAN (AZD8205) VERSUS CHEMOTHERAPY IN PATIENTS WITH B7‑H4‑SELECTED ADVANCED/METASTATIC ENDOMETRIAL CANCER (IGCS 2026) - P3 | " Approximately 700 patients will be randomized 1:1 to receive either Arm A: Puxi-Sam (2.4mg/kg intravenous on Day 1 every 3 weeks [q3w]) or Arm B: either doxorubicin (60mg/m2 intravenous on Day 1 q3w) or paclitaxel (80mg/m2 intravenous on Days 1, 8, and 15 in 28-day cycles) until radiographic disease progression, unacceptable toxicity, patient withdrawal, or discontinuation criteria are met. Study completion: July 2029. Puxi-Sam represents a potential treatment option for hard-to- treat, second-to-third-line advanced/metastatic EC."

Clinical • Metastases • P3 data • Endometrial Cancer • Oncology • Solid Tumor • VTCN1

In vivo study on heterogeneous model system demonstrates specific Puxitatug samrotecan activity and suggests bystander activity (ESMO 2026) - No abstract available

Heterogeneity • Preclinical • Oncology

Updated safety and efficacy of puxitatug samrotecan (Puxi-Sam, AZD8205) in patients (pts) with endometrial cancer (EC) or ovarian cancer (OC): Phase 1/2a BLUESTAR study. (ASCO 2026) - P1/2, P3 | "Puxi-Sam showed a favorable safety profile and robust antitumor efficacy, supporting continued development, and is now being investigated in the Phase 3 BLUESTAR-Endometrial01 (NCT07044336) study. Efficacy (interim response evaluable pts). *2 pts were non-evaluable."

Clinical • P1/2 data • Endometrial Cancer • Neutropenia • Oncology • Ovarian Cancer • Solid Tumor • VTCN1

Safety and preliminary efficacy of puxitatug samrotecan (P-Sam, AZD8205) in patients (pts) with endometrial cancer (EC): a first-in-human Phase 1/2a study (SGO 2025) - No abstract available

Clinical • Late-breaking abstract • P1/2 data • Endometrial Cancer • Oncology • Solid Tumor

Initial results from a first-in-human study of the B7-H4-directed antibody-drug conjugate (ADC) AZD8205 (puxitatug samrotecan) in patients with advanced/metastatic solid tumors (ESMO 2024) - P1/2 | "AZD8205 had a manageable safety profile consistent with other Top1i ADCs and showed preliminary efficacy in heavily pre-treated pts with prior progression on standard treatment. Phase 2 expansion cohorts are ongoing in ovarian, breast, endometrial and biliary tract cancer."

Clinical • Metastases • P1 data • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Endometrial Cancer • Gastrointestinal Cancer • Oncology • Ovarian Cancer • Solid Tumor • VTCN1

Safety and efficacy of puxitatug samrotecan (Puxi-Sam, AZD8205) in patients with biliary tract cancer (BTC): A first-in-human phase 1/2a study (BLUESTAR). (ASCO 2026) - P1/2 | "Puxi-Sam demonstrated a favorable safety profile and showed modest clinical activity with prolonged disease stabilization observed in a subset of heavily pretreated patients with nonresectable, recurrent, or metastatic BTC. Efficacy summary (interim response evaluable patients). *Full analysis set."

Clinical • First-in-human • P1/2 data • Biliary Cancer • Biliary Tract Cancer • Neutropenia • Oncology • Solid Tumor • VTCN1

Puxitatug samrotecan (P-Sam, AZD8205) in patients (pts) with HR+/HER2– breast cancer (BC): A first-in-human phase I/IIa dose escalation and expansion study (ESMO-BC 2025) - P1/2 | "P-Sam had a manageable safety profile and showed preliminary efficacy in heavily pre-treated pts with advanced/recurrent HR+/HER2‒ BC; further P-Sam development is ongoing."

Clinical • P1/2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • VTCN1

Puxitatug samrotecan: Data from P3 Bluestar-Endometrial01 trial (NCT07044336) for 2-3L endometrial cancer in H2 2027 (AstraZeneca) - H1 & Q2 2026 Results: Data from P1/2 BLUESTAR trial (NCT05123482) for solid tumors in H1 2027

P1/2 data • P3 data • Endometrial Cancer • Gynecologic Cancers • Oncology • Solid Tumor

Puxitatug Samrotecan Hits 60% Response Rate in Platinum- and IO-Pretreated Endometrial Cancer (Targeted Oncology) - "At the 2.4 mg/kg dose level in the endometrial cancer cohort (n = 51), puxitatug samrotecan produced a confirmed ORR of 47.1% (95% CI, 32.9%-61.5%), a 12-week disease control rate (DCR) of 84.3% (95% CI, 71.4%-93.0%), a median duration of response (DOR) of 7.1 months (95% CI, 4.5-13.3), and a median PFS of 7.2 months (95% CI, 5.6-9.2)...In the platinum-resistant ovarian cancer cohort at 2.4 mg/kg (n = 45), the confirmed ORR was 24.4% (95% CI, 12.9%-39.5%), 12-week DCR was 64.4% (95% CI, 48.8%-78.1%), median DOR was 7.0 months (95% CI, 4.0-14.8), and median PFS was 5.7 months (95% CI, 4.1-9.5)."

First-in-human • P1/2 data • Platinum resistant • Trial status • Endometrial Cancer • Endometrioid Carcinoma • Ovarian Cancer

Puxitatug Samrotecan (AZD8205) Monotherapy vs Chemotherapy in B7-H4-selected Endometrial Cancer (Bluestar-Endometrial01) (clinicaltrials.gov) - P3 | N=800 | Recruiting | Sponsor: AstraZeneca | Trial primary completion date: Jan 2028 ➔ Oct 2027

Monotherapy • Trial primary completion date • Endometrial Cancer • Oncology • Solid Tumor

Puxitatug samrotecan (AZD8205) vs chemotherapy in patients with B7‑H4–selected advanced/metastatic endometrial cancer: The phase 3 randomized Bluestar‑Endometrial01 (BE01)/GOG-3110/ENGOT-EN28 trial. (ASCO 2026) - P3 | "Approximately 700 pts will be randomized 1:1 to either Arm A: Puxi-Sam (2.4 mg/kg; intravenous [IV] on Day 1 every 3 weeks [q3w]) or Arm B: either doxorubicin (60 mg/m2 IV on Day 1 q3w) or paclitaxel (80 mg/m2 IV on Days 1, 8, and 15 in 28-day cycles). 2025; 200:347–348. Editorial acknowledgment: Medical writing assistance was provided by Lewis C Rodgers, PhD, of Omnicom Health Medical Communications, and was funded by AstraZeneca."

Clinical • First-in-human • IO biomarker • Metastases • P3 data • Endometrial Cancer • Oncology • Solid Tumor • VTCN1

Puxitatug samrotecan: "All pts: ORR 47.1%, mPFS 7.2 mo; In pts with prior IO: ORR 60.6%, mPFS 7.1 mo"; Endometrial Cancer (AstraZeneca) - Congress, American Society of Clinical Oncology – ASCO, Chicago [Management]

P1/2 data • Endometrial Cancer • Gynecologic Cancers • Oncology

More than 85 abstracts will feature 10 approved and 13 potential new medicines from the Company, including 25 oral presentations. Highlights include (AstraZeneca Press Release) - "BLUESTAR: Updated safety and efficacy results from the BLUESTAR Ph I/IIa trial of the B7-H4-directed ADC puxitatug samrotecan (Puxi-Sam) in patients with relapsed/metastatic B7-H4-positive endometrial and ovarian cancer...PRIMAVERA: Safety and preliminary efficacy from the first-in-human Phase I PRIMAVERA trial of the protein arginine methyltransferase 5 (PRMT5) inhibitor AZD3470 as monotherapy in relapsed/refractory classic Hodgkin lymphoma (Oral Abstract #7003)...Phase I initial results for NT-175 T-cell receptor therapy in TP53 R175H-mutated unresectable, advanced and/or metastatic solid tumours including pancreatic adenocarcinoma (Oral Abstract #2506)...POTOMAC: Five-year overall survival and patient-reported outcomes from the Phase III POTOMAC trial of Imfinzi plus Bacillus Calmette-Guérin (BCG) induction and maintenance therapy in patients with high-risk non-muscle-invasive bladder cancer (Rapid Oral Abstract #4624)."

First-in-human • P1 data • P1/2 data • P3 data • P53mut • Bladder Cancer • Breast Cancer • Classical Hodgkin Lymphoma • Colorectal Cancer • Endometrial Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Pancreatic Adenocarcinoma • Squamous Cell Carcinoma of Head and Neck

Phase II Trial of Puxitatug Samrotecan (AZD8205) in Advanced, Recurrent or Metastatic (R/M) Aggressive Adenoid Cystic Carcinoma Subtype I (ACC-I) (clinicaltrials.gov) - P2 | N=28 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Not yet recruiting ➔ Recruiting | Initiation date: Dec 2026 ➔ Apr 2026

Enrollment open • Trial initiation date • Adenoid Cystic Carcinoma • Oncology • TP63 • VTCN1

Combination of B7-H4-TOP1i ADC, PD-1/TIGIT bispecific antibody, and PARP inhibition orchestrates angiogenesis suppression and interferon-program activation in a syngeneic mouse model (AACR 2026) - P1/2 | "scRNA-seq results indicate that the studied drug combinations produce a transcriptomic remodeling characterized by coordinated tumor-cell program suppression and system-wide interferon response amplification in immune cells. AZD8205 doublet treatments deliver the most extensive tumor-intrinsic transcriptional changes, while rilvegostomig or saruparib each add orthogonal immune activation, yielding complementary and potentially synergistic pharmacodynamics that are not observed with individual drugs. The ongoing BLUESTAR clinical trial (NCT05123482) is exploring these combinations in patients."

ADC • Bispecific • IO biomarker • Preclinical • Oncology • CD8 • PD-1 • TIGIT • VTCN1

Puxitatug Samrotecan (AZD8205) Monotherapy vs Chemotherapy in B7-H4-selected Endometrial Cancer (Bluestar-Endometrial01) (clinicaltrials.gov) - P3 | N=700 | Recruiting | Sponsor: AstraZeneca | N=187 ➔ 700

Enrollment change • Monotherapy • Trial initiation date • Endometrial Cancer • Oncology • Solid Tumor

Phase II Trial of Puxitatug Samrotecan (AZD8205) in Advanced, Recurrent or Metastatic (R/M) Aggressive Adenoid Cystic Carcinoma Subtype I (ACC-I) (clinicaltrials.gov) - P2 | N=28 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center | Initiation date: Feb 2026 ➔ Dec 2026

Trial initiation date • Adenoid Cystic Carcinoma • Oncology • TP63 • VTCN1

Puxitatug Samrotecan (AZD8205) Monotherapy vs Chemotherapy in B7-H4-selected Endometrial Cancer (Bluestar-Endometrial01) (clinicaltrials.gov) - P3 | N=700 | Recruiting | Sponsor: AstraZeneca | N=183 ➔ 700 | Trial completion date: Apr 2028 ➔ Jul 2029

Enrollment change • Monotherapy • Trial completion date • Trial initiation date • Endometrial Cancer • Oncology • Solid Tumor

Puxitatug samrotecan: Data from P3 Bluestar-Endometrial01 trial (NCT07044336) for 2-3L endometrial cancer in 2027 (AstraZeneca) - FY 2025 Results: Data from P1/2 BLUESTAR trial (NCT05123482) for solid tumors in 2027

P1/2 data • P3 data • Endometrial Cancer • Gynecologic Cancers • Oncology • Solid Tumor

Puxitatug samrotecan: Data from P3 Bluestar-Endometrial01 trial (NCT07044336) for 2-3L endometrial cancer post 2026 (AstraZeneca) - Q3 2025 Results

P3 data • Endometrial Cancer • Oncology

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

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

Phase II Trial of Puxitatug Samrotecan (AZD8205) in Advanced, Recurrent or Metastatic (R/M) Aggressive Adenoid Cystic Carcinoma Subtype I (ACC-I) (clinicaltrials.gov) - P2 | N=28 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center

New P2 trial • Adenoid Cystic Carcinoma • Oncology

Puxitatug Samrotecan (AZD8205) Monotherapy vs Chemotherapy in B7-H4-selected Endometrial Cancer (Bluestar-Endometrial01) (clinicaltrials.gov) - P3 | N=700 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy • Endometrial Cancer • Oncology • Solid Tumor

Puxitatug samrotecan: Data from P1/2 trial (NCT05123482) for solid tumors post 2026 (AstraZeneca) - H1 & Q2 2025 Results

P1/2 data • Oncology • Solid Tumor