oleclumab (MEDI9447) / AstraZeneca - LARVOL DELTA

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

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

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=48 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Suspended ➔ Active, not recruiting

Enrollment closed • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • PD-L1

SYNERGY: Paclitaxel + Carboplatin + Durvalumab With or Without Oleclumab for Previously Untreated Locally Recurrent Inoperable or Metastatic TNBC (clinicaltrials.gov) - P1/2 | N=129 | Active, not recruiting | Sponsor: Jules Bordet Institute | Trial completion date: Apr 2025 ➔ Dec 2025 | Trial primary completion date: Aug 2024 ➔ Mar 2025

IO biomarker • Metastases • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD73 • ER • HER-2 • PGR

Neo-CheckRay: Neo-adjuvant Chemotherapy Combined With Stereotactic Body Radiotherapy to the Primary Tumour +/- Durvalumab, +/- Oleclumab in Luminal B Breast Cancer: (clinicaltrials.gov) - P2 | N=147 | Active, not recruiting | Sponsor: Jules Bordet Institute | Trial primary completion date: Sep 2024 ➔ May 2025

Trial primary completion date • Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2

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 | Recruiting ➔ Active, not recruiting | N=30 ➔ 13

Enrollment change • Enrollment closed • Surgery • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

TILs and PD-L1 early dynamics in the randomized Neo-CheckRay phase II trial evaluating neo-adjuvant immuno-radiation and adenosine pathway blockade for early-stage, high risk ER+/HER2- breast cancer (BC) (ESMO-IO 2024) - P2 | "Background Neo-CheckRay (NCT03875573) demonstrated high rates of pathological complete response (pCR) after immune-modulating stereotactic body radiation therapy (iSBRT) to the primary BC in combination with the anti-PD-L1 durvalumab (durva) in high-risk early-stage luminal BC...Pts were randomized 1:1:1 to ARM 1: paclitaxel q1w x12 with iSBRT at week 4 (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 q4w x5; and ARM 3 : arm 1 + durva + oleclumab (anti-CD73) q2w x4 then q4w x3...Table: 2O All Arm 1 Arm 2 Arm 3 n 135 45 45 45 pts, % B: PD-L1 negative* 58.5 57.8 57.8 60.0 W6: no tumor 32.2 13.5 46.3 34.9 W6: TILs increase 14.0 16.2 12.2 14.0 W6: PD-L1 IC increase 42.7 31 48 48 pCR rate, % All pts 28.9 17.8 33.3 35.6 B: PD-L1 negative* 24.0 3.8 34.6 33.3 W6: no tumor 48.7 40.0 47.4 53.3 W6: TILs increased 17.6 0.0 20.0 33.3 W6: PD-L1 IC increased 24.0..."

Clinical • 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 • PD-L1

A first-in-human, open-label, multicenter, phase 1/2a, dose-escalation and expansion study of GI-108, a novel immunocytokine combining anti-CD73-IL2v, in patients with metastatic solid tumors (SITC 2024) - "Preclinical studies have shown that GI-108 effectively reinvigorated CD8+ T cells even in the presence of AMP, unlike oleclumab.1 In Cynomolgus monkeys, intravenous administration of GI-108 resulted in robust increase of total lymphocytes and CD8+ T cells without significant toxicities. The primary objective of this study is to assess safety, and tolerability of GI-108 to define the MTD and/or RP2D in the dose escalation phase and to assess the anti-tumor activity of GI-108 in the dose expansion phase. Results This study is currently enrolling patients with advanced/metastatic solid tumors."

Clinical • Metastases • P1/2 data • Gastric Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CD8 • NT5E

Precision immuno-oncology for advanced non-small cell lung cancer (NSCLC) patients with PD-(L)1 inhibitors resistance (PIONeeR): A phase Ib/IIa clinical trial targeting identified resistance pathways (ESMO 2024) - P2 | "Pts were randomly allocated to Arm A: Durvalumab (Du) + Monalizumab, Arm B: Du + Oleclumab, Arm C: Du + Ceralasertib, Arm E: Du + Savolitinib or Arm D (control): Docetaxel. With its innovative and adaptive design, the PIONeeR trial was able to explore several options to overcome resistance to ICIs. Although no experimental arm performed better than outcomes observed with docetaxel, some pts had long DoR, suggesting durvalumab combinations can be highly effective. Biomarker work is ongoing to identify patients most likely to benefit from combination treatment."

Clinical • Immuno-oncology • IO biomarker • Late-breaking abstract • Metastases • P1/2 data • Lung Cancer • Non Small Cell Lung 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=30 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • 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=48 | Suspended | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Suspended

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

[PREPRINT] 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 (medRxiv) - P2 | N=25 | NCT03267589 | "At baseline, short-term and long-term survivors differed with regard to the relative abundances of total peripheral blood mononuclear cells (PBMCs). We observed a significant increase in CD14+CD16- myeloid cells during treatment, initially driven by classical monocyte proliferation and subsequently driven by the expansion of monocytic myeloid-derived suppressor cells (M-MDSCs). This M-MDSC expansion occurred only in patients with shorter progression-free survival, who also showed a continuous decrease in central memory T-cell abundances after baseline. Throughout treatment, we observed upregulation of PD-L1 expression on most T-cell subsets in all patients. Higher expression of CD73 and IDO1 on select leukocyte subsets at baseline was significantly positively correlated with longer progression-free survival."

P2 data • Preprint • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

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

NeoCOAST-2: Neoadjuvant and Adjuvant Treatment in Resectable Non-small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=490 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Dec 2029 ➔ May 2030 | Trial primary completion date: Dec 2029 ➔ May 2030

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

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=30 | Not yet recruiting | Sponsor: AstraZeneca

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