oleclumab (MEDI9447) / AstraZeneca - LARVOL DELTA

Neoadjuvant durvalumab (D) + chemotherapy (CT) + novel anticancer agents and adjuvant D ± novel agents in resectable non-small-cell lung cancer (NSCLC): Updated outcomes from NeoCOAST-2. (ASCO 2025) - P2 | " Pts were stratified by PD-L1 expression (<1% vs ≥1%) and randomized to neoadjuvant D + platinum-doublet CT + oleclumab (anti-CD73 monoclonal antibody [mAb]) then adjuvant D + oleclumab (Arm 1), neoadjuvant D + platinum-doublet CT + monalizumab (anti-NKG2A mAb) then adjuvant D + monalizumab (Arm 2), or neoadjuvant D + single-agent platinum CT + Dato-DXd (TROP2-directed antibody-drug conjugate [ADC]) then adjuvant D (Arm 4). All arms show that novel perioperative combinations may improve pCR rates and maintain tolerability and feasibility of surgery in resectable NSCLC. The final analysis of pCR and mPR rates in Arm 4 is the first for an ADC in this setting and confirms the encouraging efficacy and manageable safety profile of D + CT + Dato-DXd. Presurgical ctDNA clearance is associated with pathological responses."

Clinical • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KLRC1

The Selective Personalized Radio-Immunotherapy for Locally Advanced NSCLC Trial 2 (SPRINT2) (IASLC-WCLC 2025) - "Introduction : In the S elective P ersonalized R adio- I mmunotherapy for locally advanced N SCLC T rial (SPRINT), patients with locally advanced NSCLC (LA-NSCLC) with PD-L1 tumor proportion score (TPS) of ≥50% were treated with induction pembrolizumab, followed by a 20-fraction course of risk-adapted thoracic radiotherapy, followed by consolidation pembrolizumab to complete a 1-year treatment course...We hypothesize that dual-agent immunotherapy with durvalumab and either monalizumab or oleclumab will enhance the efficacy of the SPRINT approach...The primary study endpoint is response on FDG-PET after induction immunotherapy, evaluated using PERCIST criteria. Other endpoints include progression-free survival, overall survival, clinician- and patient-reported adverse events, and physical activity metrics captured using wearable devices."

Metastases • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor

Heating up cold tumors: single-cell mapping of immune and adenosine pathway reprogramming in luminal B breast cancer (Neo-CheckRay trial) (SABCS 2025) - P2 | "Adding durvalumab (arm 2) ± oleclumab (arm 3) to SBRT+NACT (arm 1) doubled pCR rates (from 16.7% to 33.3% and 31.1%). In contrast, non-responders and arm 1 accumulated CD73 on myeloids (p = 0.009), CAFs (p = 0.05), and epithelium (p = 0.024) while lacking degradation enzymes, maintaining suppression.ConclusionIn immune-cold luminal B breast cancer, effective therapy likely requires: pre-existing immune organization (CXCL13+ myeloid), anti-tumor priming by SBRT+NACT, sustained T-cell activity via PD-L1 blockade, and relief of adenosine-mediated suppression via CD73 blockade. Notably, our data suggest oleclumab's efficacy may stem not from mere CD73 inhibition, but from its redistribution to the vascular niche, where it may preserve perfusion and immune accessibility, without triggering the immunosuppressive effects seen with CD73 upregulation on myeloid, CAF, or epithelial cells."

IO biomarker • Breast Cancer • ADORA2A • ADORA2B • APOC1 • CD4 • CD73 • CXCL10 • CXCL13 • ENTPD1 • IL2RA • SPP1 • STING

Primary endpoint results of the Neo-CheckRay phase II trial evaluating stereotactic body radiation therapy (SBRT) +/- durvalumab (durva) +/- oleclumab (ole) combined with neo-adjuvant chemotherapy (NACT) for early-stage, high risk ER+/HER2- breast cancer (BC) (ESMO 2024) - P2 | "Neo-CheckRay (NCT03875573) is the first prospective, international, phase 2, randomized trial investigating this treatment. Eligible patients (pts) with newly diagnosed cT1c-3 (≥ 2 cm) cN0 or cT1c-3 (≥ 1.5 cm) cN1-3, grade 2 (Ki67 ≥ 15%) or grade 3, MammaPrint (MP) high risk, invasive ER+/HER2- BC were randomized 1:1:1 to arm 1: neo-adjuvant paclitaxel q1w x12 with SBRT at week 5 (3x8 Gy targeting the primary tumour, avoiding lymph nodes and normal breast tissue), followed by dose-dense epirubicin/cyclophosphamide q2w x4; arm 2: arm 1 + durva 1500mg q4w x5; and arm 3: arm 2 + ole 3000 mg q2w x4 then q4w x3. The addition of durva+/- ole numerically increases pCR and RCB 0/1 rates compared to NACT+SBRT. Final statistical analysis will be presented at the conference. Ongoing translational research will shed light on the mechanisms of response."

Clinical • Late-breaking abstract • P2 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Establishment of a humanized patient-derived xenograft mouse model of high-grade serous ovarian cancer for preclinical evaluation of combination immunotherapy. (PubMed, Mol Oncol) - "The mice were administered durvalumab (anti-PD-L1) and/or oleclumab (anti-CD73) immunotherapy intraperitoneally twice a week for 5 weeks. This model reflects the immunotherapy resistance of human disease in line with clinical findings, providing a robust platform for studying tumor-immune interactions and immunosuppressive mechanisms in HGSOC. Impact statement Our results address the critical need for representative preclinical models for testing combination immunotherapy in HGSOC by providing a robust preclinical platform that can enhance the reliability of preclinical data and contribute to the improvement of the design and outcomes of future clinical trials."

Journal • Preclinical • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor

PIONeeR: Precision Immuno-Oncology for Advanced Non-small Cell Lung Cancer Patients With PD-1 ICI Resistance (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Assistance Publique Hopitaux De Marseille | Not yet recruiting ➔ Recruiting | Trial completion date: Sep 2023 ➔ Feb 2024 | Trial primary completion date: Mar 2023 ➔ Oct 2023

Enrollment open • Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Thoracic Cancer • ALK • EGFR • ROS1

PIONeeR: Precision Immuno-Oncology for Advanced Non-small Cell Lung Cancer Patients With PD-1 ICI Resistance (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: Assistance Publique Hopitaux De Marseille

New P2 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Thoracic Cancer • ALK • EGFR • ROS1

PIONeeR: Precision Immuno-Oncology for Advanced Non-small Cell Lung Cancer Patients With PD-1 ICI Resistance (clinicaltrials.gov) - P2 | N=114 | Active, not recruiting | Sponsor: Assistance Publique Hopitaux De Marseille | Recruiting ➔ Active, not recruiting | Trial completion date: Feb 2024 ➔ Feb 2025 | Trial primary completion date: Oct 2023 ➔ Oct 2024

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

MAGELLAN: A Study of Novel Anti-cancer Agents in Patients With Previously Untreated NSCLC (clinicaltrials.gov) - P1 | N=175 | Active, not recruiting | Sponsor: AstraZeneca | Trial completion date: May 2023 ➔ Mar 2026

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

HUDSON: Phase II Umbrella Study of Novel Anti-cancer Agents in Participants With NSCLC Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy (clinicaltrials.gov) - P2 | N=531 | Active, not recruiting | Sponsor: AstraZeneca | Trial completion date: Sep 2024 ➔ Sep 2026 | Trial primary completion date: Sep 2024 ➔ Sep 2026

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

BEGONIA: A Study of Novel Anti-cancer Agents in Patients With Metastatic Triple Negative Breast Cancer (clinicaltrials.gov) - P1/2 | N=210 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1

BEGONIA: A Study of Novel Anti-cancer Agents in Patients With Metastatic Triple Negative Breast Cancer (clinicaltrials.gov) - P1/2 | N=203 | Recruiting | Sponsor: AstraZeneca | Active, not recruiting ➔ Recruiting

Enrollment open • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1

HUDSON: Phase II Umbrella Study of Novel Anti-cancer Agents in Participants With NSCLC Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy (clinicaltrials.gov) - P2 | N=320 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Jul 2021 ➔ Sep 2022 | Trial primary completion date: Jul 2021 ➔ Sep 2022

Biomarker • IO biomarker • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

BEGONIA: A Study of Novel Anti-cancer Agents in Patients With Metastatic Triple Negative Breast Cancer (clinicaltrials.gov) - P1/2 | N=243 | Active, not recruiting | Sponsor: AstraZeneca | Trial completion date: Nov 2024 ➔ Feb 2027

Trial completion date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1

BEGONIA: A Study of Novel Anti-cancer Agents in Patients With Metastatic Triple Negative Breast Cancer (clinicaltrials.gov) - P1/2 | N=200 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Aug 2022 ➔ Feb 2023 | Trial primary completion date: Aug 2022 ➔ Feb 2023

Trial completion date • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1

MAGELLAN: A Study of Novel Anti-cancer Agents in Patients With Previously Untreated NSCLC (clinicaltrials.gov) - P1 | N=175 | Active, not recruiting | Sponsor: AstraZeneca | N=258 ➔ 175 | Trial completion date: Mar 2026 ➔ May 2023 | Trial primary completion date: Mar 2026 ➔ May 2023

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

BEGONIA: A Study of Novel Anti-cancer Agents in Patients With Metastatic Triple Negative Breast Cancer (clinicaltrials.gov) - P1/2 | N=100 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Jun 2022 ➔ Dec 2020

Trial completion date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1

Establishment of a humanized patient-derived xenograft mouse model of high-grade serous ovarian cancer for preclinical evaluation of combination immunotherapy (ESGO 2026) - "The mice were administered durvalumab and/or oleclumab intraperitoneally semi-weekly for five weeks. No significant inter-group differences in disease burden, intratumoral leukocyte density, or circulating T cells were observed. In the durvalumab-only group, tumor burden significantly positively correlated with intratumoral cytotoxic (r = 0.9524; R2 = 0.907; p = 0.0476) and regulatory T-cell (r = 0.9614; R2 = 0.924; p = 0.0386) densities.Conclusion This model accurately reflects human disease biology and clinical findings, providing a robust platform for studying tumor-immune interactions and immunosuppressive mechanisms in HGSOC."

Preclinical • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • CD73

HUDSON: Phase II Umbrella Study of Novel Anti-cancer Agents in Participants With NSCLC Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy (clinicaltrials.gov) - P2 | N=200 | Not yet recruiting | Sponsor: AstraZeneca

Biomarker • IO biomarker • New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

HUDSON: Phase II Umbrella Study of Novel Anti-cancer Agents in Participants With NSCLC Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy (clinicaltrials.gov) - P2 | N=420 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Oct 2023 ➔ Aug 2024 | Trial primary completion date: Oct 2023 ➔ Aug 2024

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

HUDSON: Phase II Umbrella Study of Novel Anti-cancer Agents in Participants With NSCLC Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy (clinicaltrials.gov) - P2 | N=570 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Jan 2026 ➔ Feb 2025 | Trial primary completion date: Jan 2026 ➔ Feb 2025

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

HUDSON: Phase II Umbrella Study of Novel Anti-cancer Agents in Participants With NSCLC Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy (clinicaltrials.gov) - P2 | N=420 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Jun 2023 ➔ Oct 2023 | Trial primary completion date: Jun 2023 ➔ Oct 2023

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

BEGONIA: A Study of Novel Anti-cancer Agents in Patients With Metastatic Triple Negative Breast Cancer (clinicaltrials.gov) - P1/2 | N=240 | Active, not recruiting | Sponsor: AstraZeneca | Trial completion date: Jun 2023 ➔ Aug 2024 | Trial primary completion date: Jun 2023 ➔ Aug 2024

Trial completion date • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1

HUDSON: Phase II Umbrella Study of Novel Anti-cancer Agents in Participants With NSCLC Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting | Trial primary completion date: Jul 2020 ➔ Nov 2020

Biomarker • Enrollment open • IO biomarker • Trial primary completion date • Non Small Cell Lung Cancer

BEGONIA: A Study of Novel Anti-cancer Agents in Patients With Metastatic Triple Negative Breast Cancer (clinicaltrials.gov) - P1/2 | N=240 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Aug 2024 ➔ Nov 2024 | Trial primary completion date: Aug 2024 ➔ Nov 2024

Trial completion date • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1