oleclumab (MEDI9447) / AstraZeneca - LARVOL DELTA

COLUMBIA 1: COLUMBIA-1: Novel Oncology Therapies in Combination With Chemotherapy and Bevacizumab as First- Line Therapy in MSS-CRC (clinicaltrials.gov) - P1/2 | N=61 | Active, not recruiting | Sponsor: MedImmune LLC | Trial completion date: Nov 2025 ➔ Nov 2026

Trial completion date • Colorectal Cancer • Oncology • Solid Tumor

MAGELLAN arms B1 and B3: Durvalumab plus chemotherapy with and without oleclumab in treatment-naïve metastatic non-small-cell lung cancer. (PubMed, Lung Cancer) - P1 | "No new safety signals were identified for durvalumab + chemotherapy ± oleclumab in patients with mNSCLC and PD-L1 expression < 50 %. The lack of meaningful efficacy improvements limits potential further development of this combination in this disease setting."

IO biomarker • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Stromal CD73 expression in early-stage high-risk luminal B-like breast cancer: An exploratory analysis from the randomized Neo-CheckRay trial (ESMO-IO 2025) - P2 | "Patients were treated with neoadjuvant anthracyclines-taxanes chemotherapy + radiation therapy 3 x 8 Gy (Arm 1) +/- durvalumab (Arm 2) +/- oleclumab (anti-CD73) (Arm 3). Our data suggest that low stromal CD73 might be associated with treatment response particularly in patients treated with an adenosine pathway blocker. Its potential as a biomarker in luminal B breast cancer warrants further investigation.Clinical trial identification NCT03875573.Legal entity responsible for the study Institut Jules Bordet."

Clinical • IO biomarker • Stroma • Breast Cancer • Oncology • Solid Tumor • CD73 • NT5E • PD-L1

Outcomes with first-line treatments for patients with locally advanced or metastatic triple negative breast cancer eligible for anti-PD-(L)1 therapy: A systematic literature review of randomized trials (SABCS 2025) - "Adding atezolizumab to taxane-based chemotherapies (7.2-7.5 vs. 5.3-6.4 months)—but not gemcitabine-carboplatin or capecitabine (4.2 vs. 3.6 months)—resulted in a significant PFS benefit...There were also statistically significant improvements in PFS with molecular subtyping-based treatments and a numerical improvement in PFS when replacing nab-paclitaxel with sacituzumab govitecan (SG) combined with immunotherapy...Conversely, trials evaluating the addition of oleclumab, nivolumab, or ipatasertib to chemotherapy and/or immunotherapy did not significantly improve PFS.Median OS ranged from 10.7-32.8 months across trials; most showed no significant differences between treatment arms... This review indicates an evolving treatment landscape, with the adoption of regimens with atezolizumab, toripalimab, pembrolizumab, and SG being associated with improved efficacy in patients with PD-(L)1-eligible LA/mTNBC. Specifically, the most recent publication revealed that SG in..."

Clinical • Metastases • Review • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

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

Gemcitabine, Nab-paclitaxel, Durvalumab, and Oleclumab Before Surgery for the Treatment of in Resectable/Borderline Resectable Primary Pancreatic Cancer (clinicaltrials.gov) - P2 | N=13 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Oct 2025 ➔ Oct 2027 | Trial primary completion date: Oct 2025 ➔ Oct 2027

Trial completion date • Trial primary completion date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

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

Testing the Safety of Adding Either Monalizumab (IPH2201) or Oleclumab (MEDI9447) to Durvalumab (MEDI4736) Plus Standard Radiation Therapy for Locally Advanced Non-small Cell Lung Cancer (NSCLC), ARCHON-1 Trial (clinicaltrials.gov) - P1 | N=26 | Completed | Sponsor: National Cancer Institute (NCI) | Trial completion date: Apr 2026 ➔ Sep 2025 | Active, not recruiting ➔ Completed

Trial completion • Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • PD-L1

SPRINT 2: The Selective Personalized Radio-Immunotherapy for Locally Advanced Non-Small Cell Lung Cancer Trial 2 (clinicaltrials.gov) - P2 | N=52 | Not yet recruiting | Sponsor: Montefiore Medical Center

New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

COLUMBIA 1: COLUMBIA-1: Novel Oncology Therapies in Combination With Chemotherapy and Bevacizumab as First- Line Therapy in MSS-CRC (clinicaltrials.gov) - P1/2 | N=61 | Active, not recruiting | Sponsor: MedImmune LLC | Terminated ➔ Active, not recruiting | Trial completion date: Oct 2022 ➔ Nov 2025

Enrollment closed • Trial completion date • Colorectal Cancer • Oncology • Solid Tumor

PACIFIC-9: A Global Study to Assess the Effects of Durvalumab With Oleclumab or Durvalumab With Monalizumab Following Concurrent Chemoradiation in Patients With Stage III Unresectable Non-Small Cell Lung Cancer (clinicaltrials.gov) - P3 | N=1027 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • PD-L1

Durvalumab Alone or Combined With Novel Agents for Unresectable Stage III Non-Small Cell Lung Cancer: Update From the COAST Randomized Clinical Trial. (PubMed, JAMA Netw Open) - P2 | "Novel immunotherapy combinations involving the anti-CD73 monoclonal antibody oleclumab or the anti-NKG2A monoclonal antibody monalizumab have the potential to build on the durvalumab standard of care. This finding supports further investigation of these novel combinations in the phase 3 PACIFIC-9 trial. ClinicalTrials.gov Identifier: NCT03822351."

Clinical • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KLRC1

First-line durvalumab plus chemotherapy with or without oleclumab for locally advanced or metastatic triple-negative breast cancer: SYNERGY overall survival and circulating tumor DNA analysis. (ASCO 2025) - P1/2 | " 133 patients received weekly carboplatin and paclitaxel x12 plus durvalumab, with (arm A) or without (arm B) oleclumab (6 in phase I, 63 in arm A, 64 in arm B). The addition of oleclumab to chemo-immunotherapy did not improve PFS or OS in advanced TNBC. However, a subgroup of patients experienced exceptional long-lasting response, indicating potential benefit in selected cases. CtDNA detection was strongly associated with poorer outcomes at all timepoints, underscoring its potential as a biomarker in this disease/setting."

Circulating tumor DNA • Clinical • IO biomarker • Metastases • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

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

Perioperative durvalumab plus chemotherapy plus new agents for resectable non-small-cell lung cancer: the platform phase II NeoCOAST-2 trial. (PubMed, Nat Med) - P2 | "In the phase II NeoCOAST-2 platform study, 202 patients with untreated, resectable stage IIA-IIIB non-small-cell lung cancer (NSCLC) were randomized to receive neoadjuvant durvalumab plus platinum-doublet chemotherapy with oleclumab, a CD73 inhibitor (Arm 1), or with monalizumab, a NKG2A inhibitor (Arm 2), or neoadjuvant durvalumab plus single-agent platinum chemotherapy with the TROP-2 antibody-drug conjugate (ADC) datopotamab deruxtecan (Arm 4), followed by surgical resection and adjuvant durvalumab with oleclumab or monalizumab (Arms 1 and 2) or durvalumab alone (Arm 4). In NeoCOAST-2, the first neoadjuvant trial examining an ADC plus chemo-immunotherapy in resectable NSCLC, pCR rates were highest in the datopotamab-deruxtecan-containing arm, warranting further investigation in larger trials of ADCs and checkpoint inhibition in the neoadjuvant setting. ClinicalTrials.gov identifier: NCT05061550 ."

Journal • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD73 • KLRC1

HUDSON: Phase II Umbrella Study of Novel Anti-cancer Agents in Patients With NSCLC Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy (clinicaltrials.gov) - P2 | N=527 | Active, not recruiting | Sponsor: AstraZeneca | Trial primary completion date: Sep 2026 ➔ Sep 2024

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

Testing the Safety of Adding Either Monalizumab (IPH2201) or Oleclumab (MEDI9447) to Durvalumab (MEDI4736) Plus Standard Radiation Therapy for Locally Advanced Non-small Cell Lung Cancer (NSCLC), ARCHON-1 Trial (clinicaltrials.gov) - P1 | N=26 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | N=48 ➔ 26 | Trial completion date: Mar 2025 ➔ Apr 2026

Enrollment change • Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • PD-L1

DOSa: Oleclumab and Durvalumab for the Treatment of Recurrent, Refractory, or Metastatic Sarcoma (clinicaltrials.gov) - P2 | N=75 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Recruiting ➔ Active, not recruiting

Enrollment closed • Angiosarcoma • Liposarcoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Adapting radiation therapy to immunotherapy: Delineation and treatment planning of pre-operative immune-modulating breast iSBRT in 151 patients treated in the randomized phase II Neo-CheckRay trial. (PubMed, Radiother Oncol) - "In the Neo-CheckRay trial, the predefined organs at risk dose constraints were feasible and the TDLN were adequately spared."

Journal • P2 data • Breast Cancer • Oncology • Solid Tumor

A Study to Investigate the Effects of Durvalumab With Oleclumab Following Chemoradiation in Participants With Locally Advanced Unresectable Non-Small Cell Lung Cancer (LADOGA) (clinicaltrials.gov) - P2 | N=28 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

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

Oleclumab (MEDI9447) Epidermal Growth Factor Receptor Mutant (EGFRm) Non-small Cell Lung Cancer (NSCLC) Novel Combination Study (clinicaltrials.gov) - P1/2 | N=43 | Active, not recruiting | Sponsor: MedImmune LLC | Trial completion date: Jul 2025 ➔ Mar 2026

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

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

Peripheral blood leukocyte signatures as biomarkers in relapsed ovarian cancer patients receiving combined anti-CD73/anti-PD-L1 immunotherapy in arm A of the NSGO-OV-UMB1/ENGOT-OV30 trial. (PubMed, Mol Oncol) - "Here, we used a 40-marker suspension mass cytometry panel to comprehensively phenotype peripheral blood leukocytes sampled over time from patients with relapsed EOC who underwent combination oleclumab (anti-CD73) and durvalumab (anti-PD-L1) immunotherapy in the NSGO-OV-UMB1/ENGOT-OV30 trial. Higher CD73 and IDO1 expression on certain leukocytes at baseline significantly positively correlated with longer progression-free survival. Overall, our study proposes potential biomarkers for EOC immunotherapy personalization and response monitoring; however, further validation in larger studies is needed."

Biomarker • IO biomarker • Journal • Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • CD14 • IDO1

A Systematic Literature Review (SLR) of the Clinical Efficacy and Safety Evidence Associated With Treatments for Patients With Metastatic Non-Small Cell Lung Cancer (NSCLC) Who Progressed on Prior Therapies (ISPOR-EU 2024) - "Median overall survival (OS) (n=37) ranged from 3.4 (any third-line [3L] treatment following docetaxel+ramucirumab) to 22.8 months (durvalumab+ceralasertib); it was not estimable in 5 studies...Only 3 studies reported significant differences (p<0.05) in OS between treatments; including pembrolizumab+ramucirumab versus standard of care. Median progression-free survival (n=35) ranged from 1.4 (durvalumab+olaparib; durvalumab+oleclumab) to 12.3 months (docetaxel+ramucirumab); it was not estimable in 1 study (platinum/non-platinum-based chemotherapy). Overall objective response (n=31) ranged from 0% (multiple treatments including durvalumab+danvatirsen) to 100% (3L single-agent chemotherapy). Discontinuations due to adverse events (AEs; n=14) ranged from 0% (atezolizumab) to 40% of patients (nintedanib+docetaxel)... Outcomes with current treatments after progression on platinum-based chemotherapy and anti-PD-1/PD-L1 inhibitors remain poor, highlighting an unmet medical..."

Clinical • Metastases • Review • Anemia • Fatigue • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

HUDSON: Phase II Umbrella Study of Novel Anti-cancer Agents in Patients 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