AZD8205

Shows activity

Also known as:

puxitatug samrotecan

Cancer types include:

breast cancer non-small cell lung cancer ovarian cancer small cell lung cancer uterine cancer

HealthScout AI Analysis

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Overview

AZD8205 (puxitatug samrotecan) is an investigational antibody–drug conjugate (ADC) being developed by AstraZeneca for B7‑H4–expressing solid tumors. Early clinical data from the ongoing first‑in‑human Phase 1/2a BLUESTAR study (NCT05123482) show preliminary activity with a manageable safety profile in heavily pretreated patients across several tumor types, with particularly encouraging signals in endometrial cancer. (ascopubs.org)

Mechanism of action

Target: B7‑H4 (VTCN1), an immune‑regulatory protein highly expressed in multiple solid tumors and limited in normal tissues. The ADC comprises a human anti–B7‑H4 antibody linked to a topoisomerase I inhibitor payload. (ascopubs.org)
Payload/linker: Preclinical work identified a bystander‑capable Val‑Ala–PEG8 linker conjugated to the novel TOP1 inhibitor AZ14170133 (“samrotecan”) at drug–antibody ratio (DAR) 8, selected for stability and efficacy. (aacrjournals.org)
Antitumor activity (preclinical): Single IV doses produced tumor regressions in patient‑derived xenograft (PDX) models; responses correlated with homologous recombination repair deficiency and with B7‑H4 levels in HRR‑proficient models. Combination with the PARP1‑selective inhibitor AZD5305 enhanced activity, including in low‑B7‑H4 models. (aacrjournals.org)

Clinical development

Trial: BLUESTAR (NCT05123482), a multi‑center, open‑label Phase 1/2a monotherapy and combination master protocol in advanced solid tumors (ovarian, breast, endometrial, biliary tract/cholangiocarcinoma; later including squamous NSCLC in combinations). Start October 2021; estimated completion March 2027. Combination cohorts include AZD5305 (saruparib) and the PD‑1/TIGIT bispecific rilvegostomig (AZD2936). (clinicaltrials.ucbraid.org)

Efficacy

Dose‑escalation/early expansion (ESMO 2024): Among 43 patients treated at doses ≥1.6 mg/kg Q3W, 9 had confirmed partial responses (20.9%) across ovarian, breast, and endometrial cancers. (oncologypro.esmo.org)
Endometrial cancer expansion (SGO 2025 update): In B7‑H4–positive advanced/recurrent endometrial cancer, objective response rate (ORR) was 34.6% at 2.0 mg/kg (n=26 evaluable) and 38.5% at 2.4 mg/kg (n=26 evaluable); 12‑week disease control rate (DCR) 80.8% and 84.6%, respectively; median progression‑free survival (PFS) ~7.0 months at both doses (median follow‑up ~4 months). (cancernetwork.com)
Conference coverage reporting from SGO 2025 is consistent, citing ORR roughly 35–42% and median PFS ~7 months. (hmpgloballearningnetwork.com)

Note: These are preliminary, non‑comparative results from an ongoing early‑phase study; randomized data are not yet available. (fdaaa.trialstracker.net)

Safety

Overall safety (ESMO 2024): Any‑grade treatment‑emergent adverse events (TEAEs) in 97.8%; most common were nausea (58.7%), neutropenia (56.5%), and anemia (50.0%). Grade ≥3 TEAEs in 82.6%, most commonly neutropenia (37.0%) and anemia (30.4%). Dose‑limiting toxicities at 3.2 mg/kg included decreased neutrophils and platelets; 4.3% discontinued due to TEAEs. Safety profile was considered consistent with other TOP1‑inhibitor ADCs. (oncologypro.esmo.org)
Endometrial cohort (SGO 2025 coverage): Common events included decreased neutrophil count, anemia, and decreased white blood cell count; grade ≥3 treatment‑related AEs occurred in 11 patients (2.0 mg/kg) and 9 patients (2.4 mg/kg); no treatment discontinuations reported in this cohort; some dose reductions occurred. (hmpgloballearningnetwork.com)

Active trials using AZD8205

Found 2 active trials using this drug:

Puxitatug Samrotecan (AZD8205) Monotherapy vs Chemotherapy in B7-H4 Selected Advanced/Metastatic Endometrial Cancer Who Progressed On or After Platinum Based Chemotherapy and Anti-PD-1/Anti-PD-L1 Therapy (Bluestar-Endometrial01)

Sponsor: AstraZeneca (industry) Phase: 3 Start date: Aug. 1, 2025

HealthScout AI summary: Adults with B7-H4–positive recurrent/metastatic endometrial carcinoma or carcinosarcoma after platinum and anti–PD-1/PD-L1 therapy (≤2 prior lines) are randomized to the B7-H4–targeted antibody–drug conjugate puxitatug samrotecan (AZD8205, delivers a topoisomerase I inhibitor payload) every 3 weeks versus physician’s choice single-agent chemotherapy (doxorubicin or paclitaxel). Key exclusions include prior TOP1 inhibitor or B7-H4–targeted therapy, ILD/pneumonitis, and platinum-sensitive (>12 months) recurrence without subsequent platinum in the recurrent setting.

ClinicalTrials.gov ID: NCT07044336

A Phase I/IIa Multi-center, Open-label Master Protocol Dose Escalation and Expansion Study of AZD8205 as Monotherapy and in Combination With Anticancer Agents in Participants With Advanced Solid Tumors (BLUESTAR)

Sponsor: AstraZeneca (industry) Phase: 1/2 Start date: Oct. 18, 2021

HealthScout AI summary: This trial enrolls adults with relapsed or metastatic solid tumors—particularly breast, ovarian, endometrial, biliary tract, and squamous NSCLC—who have received prior therapy, evaluating the antibody-drug conjugate AZD8205 (targets B7-H4 and delivers a topoisomerase I inhibitor) as monotherapy or in combination with the PD-1/TIGIT bispecific antibody rilvegostomig or the PARP inhibitor saruparib. Eligible patients must have measurable disease, ECOG 0-1, and adequate organ function, with some sub-studies focusing on select tumor types.

ClinicalTrials.gov ID: NCT05123482