monalizumab (IPH2201) / AstraZeneca, Innate - LARVOL DELTA

Multimodal single-cell profilingidentifies an actionableNKG2A-HLA-E immune checkpoint in IDH-mutant gliomas (EANO 2026) - "Our results highlight the presence of an actionable NKG2A-HLA-E immune checkpoint in IDH-mutant gliomas. These findings support the therapeutic potential of NKG2A blockade, such as monalizumab, to activate NK and CD8⁺ T cells and promote antitumor immunity. Furthermore, as IDH-mutant inhibitors may enhance tumor immunogenicity and immune infiltration, their combination with NKG2A-targeted therapies may represent a promising strategy for these patients."

IO biomarker • Brain Cancer • Glioma • Oncology • Solid Tumor • CD8 • HLA-E • KLRC1 • OLIG2 • PRF1

COAST: An Open-Label, Phase II, Multidrug Platform Study of Durvalumab Alone or in Combination With Oleclumab or Monalizumab in Patients With Unresectable, Stage III Non-Small-Cell Lung Cancer. (PubMed, J Clin Oncol) - "Both combinations increased ORR and prolonged PFS versus durvalumab alone. Safety was similar across arms with no new or significant safety signals identified with either combination. These data support their further evaluation in a phase III trial."

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

Single-cell transcriptomics reveals an immunosuppressive axis driven by CXCL13+NK and TOX+T cells in refractory ENKTL (ECP 2026) - "Therefore, targeting NKG2A (e.g., with Monalizumab) may effectively block this immunosuppressive pathway... R/R ENKTL is characterized by a immunosuppressive TME orchestrated by CXCL13+ NK and TOX+ T cells via NKG2A and CSF1R pathways. Targeting NKG2A, OPRM1, or CXCL13 may offer novel therapeutic opportunities for improving outcomes in R/R ENKTL."

Extranodal Natural Killer/T-cell Lymphoma • Hematological Malignancies • Lymphoma • Natural Killer/T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • CCR8 • CSF1R • CXCL10 • CXCL13 • HLA-E • KLRC1 • OPRM1 • TNFRSF14

Platform study of neoadjuvant durvalumab (D) alone or combined with novel agents in patients (pts) with resectable, early-stage non-small cell lung cancer (NSCLC): Pharmacodynamic correlates and circulating tumor DNA (ctDNA) dynamics in the NeoCOAST study (ESMO 2022) - P2 | "NeoCOAST (NCT03794544) is a phase 2 study of the anti-PD-L1 monoclonal antibody (mAb) D alone or combined with the anti-CD73 mAb oleclumab (O), the anti-NKG2A mAb monalizumab (M), or the anti-STAT3 antisense oligonucleotide danvatirsen (Da) as neoadjuvant therapy. Association of tumor mutational burden and additional biomarkers with clinical outcomes will be reported. Conclusions Single cycle of D+O and D+M resulted in greater intra-tumoral immunomodulation than D alone."

Circulating tumor DNA • Clinical • IO biomarker • PK/PD data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CD8 • EGFR • KLRC1 • KRAS • STAT3 • STK11 • TMB

Pipeline highlights: Monalizumab (anti-NKG2A antibody), developed in collaboration with AstraZeneca (Businesswire) - "PACIFIC-9 is an AstraZeneca-sponsored Phase 3 study evaluating durvalumab in combination with monalizumab or oleclumab in patients with unresectable Stage III NSCLC who have not progressed following platinum-based chemoradiation therapy (CRT). Enrollment in the trial is complete, and data readout is expected in H2 2026."

Enrollment closed • P3 data • Non Small Cell Lung 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

Neoadjuvant Durvalumab Alone or Combined with Novel Immuno-Oncology Agents in Resectable Lung Cancer: The Phase 2 NeoCOAST Platform Trial. (PubMed, Cancer Discov) - "Eighty-three patients received a single cycle of treatment: 26 received durvalumab (anti-PD-L1) monotherapy, 21 received durvalumab plus oleclumab (anti-CD73), 20 received durvalumab plus monalizumab (anti-NKG2A), and 16 received durvalumab plus danvatirsen (anti-STAT3 antisense oligonucleotide). Safety profiles for the combinations were similar to that of durvalumab alone. Multiplatform immune profiling suggested improved MPR rates in the durvalumab plus oleclumab and durvalumab plus monalizumab arms were associated with enhanced effector immune infiltration of tumors, interferon responses and markers of tertiary lymphoid structure formation, and systemic functional immune-cell activation."

Immuno-oncology • IO biomarker • Journal • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KLRC1 • STAT3

Neocoast-2: Efficacy and Safety of Neoadjuvant Durvalumab (D) + Novel Anticancer Agents + CT and Adjuvant D ± Novel Agents in Resectable NSCLC (IASLC-WCLC 2024) - P2 | "Methods : Patients with untreated, histologicallyconfirmed, resectable Stage IIA-IIIB NSCLC were stratified by PD-L1 expression(<1% vs ≥1%) and randomised to Arm 1: neoadjuvant D + platinum-doublet CT +oleclumab (anti-CD73 mAb), Arm 2: D + platinum-doublet CT + monalizumab (anti-NKG2AmAb), or Arm 4: D + single-agent platinum CT + Dato-DXd (TROP2 directed antibody-drug conjugate [ADC]).Neoadjuvant therapy was given Q3W for 4 cycles prior to surgery, followed byadjuvant treatment with D + oleclumab (Arm 1) or monalizumab (Arm 2) or alone(Arm 4) until disease progression per RECIST v1.1 or for up to 1 year. Treatments in all arms led to improvementsin mPR rates along with a manageable safety profile and surgical ratescomparable to currently approved neoadjuvant and perioperativeimmunotherapy-based regimens (Forde NEJM 2022; Wakelee NEJM 2023). This is the first global Ph2 platform study showing encouragingefficacy and a manageable safety profile of an ADC in the..."

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

Updated results from COAST, a phase 2 study of durvalumab (D) ± oleclumab (O) or monalizumab (M) in patients (pts) with stage III unresectable non-small cell lung cancer (uNSCLC). (ASCO 2024) - P2, P3 | "D+O and D+M increased ORR and prolonged PFS and OS vs D alone. Safety was similar across arms, with no new safety signals. Further investigation of D, D+O, and D+M in this population is ongoing in the Phase 3 PACIFIC-9 study (NCT05221840)."

Clinical • IO biomarker • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Solid Tumor • HLA-E • KLRC1 • NT5E • PD-L1

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

NeoCOAST: open-label, randomized, phase 2, multidrug platform study of neoadjuvant durvalumab alone or combined with novel agents in patients (pts) with resectable, early-stage non-small-cell lung cancer (NSCLC) (AACR 2022) - P2 | "NeoCOAST (NCT03794544) is a global, randomized phase 2 study of the anti-PD-L1 monoclonal antibody (mAb) durvalumab (D) alone or combined with the anti-CD73 mAb oleclumab (O), the anti-NKG2A mAb monalizumab (M), or the anti-STAT3 antisense oligonucleotide danvatirsen (Da) as neoadjuvant therapy. Pts with previously untreated, cytologically/histologically documented, resectable, Stage I [>2 cm]-IIIA NSCLC and ECOG PS 0-1 were randomized 1:1:1:1 (stratified by lymph node involvement) to receive D 1500 mg IV alone Q4W or combined with O 3000 mg IV Q2W, M 750 mg IV Q2W, or Da 200 mg IV QW, for one 28-day cycle, followed by surgery. One cycle of D + O, M or Da improved MPR and pCR rates vs D alone, with no new safety signals. Responses were associated with baseline tumor PD-L1 and CD73 expression levels. Pts with MPR receiving D+O or D+M had peripheral transcriptomic signatures related to immune cell function."

Clinical • IO biomarker • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KLRC1 • NT5E • STAT3

Combination Strategies Enhance NK Cell Therapy for Multiple Myeloma (MM): Memory-like Differentiation, NKG2A Blockade, and Improved Recognition Via BCMA CAR or MM-Targeting Antibodies (TCT-ASTCT-CIBMTR 2025) - "Human NK cells were adoptively transferred into MM-bearing NSG mice to test ML differentiation, NKG2A blockade (monalizumab, IgG4), and BCMA CAR, or combinations, for pre-clinical activity...To complement these strategies, we tested anti-SLAMF7 mAb (elotuzumab) and BMCA CAR (41BB,CD3z) with ML NK cell differentiation... MM patient blood NK cells are functionally intact, and ML differentiation, NKG2A checkpoint blockade, and use of CAR or MM-targeting mAb to enhance recognition significantly improve NK cell anti-MM attack. However, combinations of these resulted in marked improvements to NK cell control of MM. These combinations for anti-MM NK cellular therapy warrant further study in early phase clinical trials."

IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • HLA-E • IFNG • IL12A • IL15 • IL18 • KLRC1 • NKG2D • SLAMF7

Unleashing NK- and CD8 T cells by combining monalizumab and trastuzumab for metastatic HER2-positive breast cancer: Results of the MIMOSA trial. (PubMed, Breast) - "Therefore, the MIMOSA-trial did not meet its primary endpoint. In summary, despite the strong preclinical rationale, the novel combination of monalizumab and trastuzumab does not induce objective responses in heavily pre-treated HER2-positive MBC patients."

Journal • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Immune Modulation • Oncology • Solid Tumor • CD8 • HER-2 • KLRC1

Phase 3 Study of Durvalumab Combined with Oleclumab or Monalizumab in Patients with Unresectable Stage III NSCLC (PACIFIC-9) (IASLC-WCLC 2022) - P2, P3 | "Other secondary endpoints include objective response rate and duration of response (RECIST v1.1; BICR), patient-reported outcomes, PD-L1 expression on tumor cells relative to efficacy outcomes, and safety/tolerability. Enrolment in PACIFIC-9 is ongoing."

Clinical • IO biomarker • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CD8 • EGFR • HLA-E • KLRC1 • TIGIT

Innate Pharma SA…announced that, subject to the closing of its strategic partnership with Sobi, it plans to initiate the TELLOMAK-3 confirmatory Phase 3 study of lacutamab in cutaneous T-cell lymphoma (CTCL) (Businesswire) - "The planned initiation of the TELLOMAK-3 confirmatory Phase 3 study marks an important step for Innate as the Company enters a new phase of late-stage clinical and regulatory execution. Under the agreement, Innate will conduct the TELLOMAK-3 Phase 3 confirmatory trial in cutaneous T-cell lymphoma, supporting a planned accelerated approval filing in Sézary syndrome (SS), based on TELLOMAK Phase 2 data. Alongside upcoming developments for IPH4502 and monalizumab, the Company is focused on executing its key clinical and regulatory priorities."

Licensing / partnership • Cutaneous T-cell Lymphoma • Sezary Syndrome

PACIFIC-9: Phase III trial of durvalumab + oleclumab or monalizumab in unresectable stage III non-small-cell lung cancer. (PubMed, Future Oncol) - P3 | "Both agents demonstrated antitumor activity in early-phase trials. PACIFIC-9 (NCT05221840) is an international, double-blind, randomized, placebo-controlled, Phase III trial comparing durvalumab plus either oleclumab or monalizumab with durvalumab plus placebo in patients with unresectable, stage III NSCLC and no disease progression following cCRT.Clinical Trial Registration: NCT05221840 (ClinicalTrials.gov)."

Journal • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD73 • KLRC1

Phase 1/2 study of monalizumab plus durvalumab in patients with advanced solid tumors. (PubMed, J Immunother Cancer) - P1/2 | "Although efficacy was modest, monalizumab plus durvalumab was well tolerated and encouraging immune activation was observed in the peripheral blood and TME."

Journal • Metastases • P1/2 data • P2 data • Cervical Cancer • Colorectal Cancer • Dermatology • Endometrial Cancer • Fatigue • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pruritus • Solid Tumor • CXCL10 • CXCL11 • GZMB • KLRC1 • KLRD1

A Study of Durvalumab (MEDI4736) and Monalizumab in Solid Tumors (clinicaltrials.gov) - P1/2 | N=383 | Active, not recruiting | Sponsor: MedImmune LLC | Trial completion date: Sep 2025 ➔ Jul 2027

IO biomarker • Trial completion date • Colorectal Cancer • Endometrial Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRAF • PD-L1

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=1051 | Active, not recruiting | Sponsor: AstraZeneca | Trial primary completion date: Jun 2026 ➔ Sep 2026

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

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

ENGINEERING CLL-1 CAR-NK CELLS VIA MRNA–LNP FOR POTENT ANTITUMOR ACTIVITY AND REVERSAL OF HLA-E–MEDIATED RESISTANCE IN ACUTE MYELOID LEUKEMIA (EHA 2026) - "(A) Schematic of ex vivo drug response analysis in three independent AML cohorts (FPMTB, BeatAML, and Qin et al.), focusing on key first-line agents including cytarabine, daunorubicin, venetoclax, azacitidine, idarubicin, and decitabine. (Q) BLI of mice treated with PBS, CAR-NK cells, or CAR-NK cells in combination with monalizumab at days 6, 12, 19, and 23. (R) Western blots of JAK2–STAT1 pathway activation and HLA-E expression in THP-1 cells co-cultured with CAR-NK cell, JAK2–STAT1 pathway activation and total HLA-E expression in THP-1 cells expressing scramble control or JAK2 shRNA after 24 h of CAR-NK co-culture or IFN- γ treatment."

IO biomarker • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • HLA-E • JAK1 • JAK3 • KLRC1 • LAMP1 • NCAM1 • NKG2D • PTPRC • STAT2 • STAT3 • STAT5 • STAT5B

Real-world efficacy of cetuximab after immune checkpoint inhibitor and platin failure in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC): A 10-year retrospective study in 124 patients. (ASCO 2026) - " Since 2015, we retrospectively analyzed all medical records of patient treated with cetuximab in a single institution, the Centre Leon Berard in France, who were in failure after IO (pembrolizumab, nivolumab, ipilimumab, atezolizumab, tremelimumab, lirimumab, FS-118 or durvalumab) and platin for R/M HNSCC. Off-label panitumumab after hypersensitivity to cetuximab, or combination with monalizumab (based on the negative results of the INTERLINK-1 trial) were allowed... This study reports a high ORR of 32.3%after use of IO, significantly exceeding historical data. No impact of the time interval between IO and cetuximab was observed and ancillary studies are needed to undestand this higher ORR. That supports ongoing trials exploring IO and anti-EGFR combinations."

Checkpoint inhibition • IO biomarker • Metastases • Real-world • Real-world effectiveness • Real-world evidence • Retrospective data • Head and Neck Cancer • Immunology • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

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 | Trial completion date: Oct 2028 ➔ Feb 2029 | Initiation date: May 2026 ➔ Sep 2026 | Trial primary completion date: Dec 2027 ➔ Apr 2028

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

Monalizumab plus durvalumab plus platinum-based chemotherapy for first-line treatment of extensive stage small-cell lung cancer: Early efficacy results from MOZART trial. (ASCO 2026) - P2 | " We conducted a single arm, multicenter, investigator-initiated phase II study with a safety lead-in cohort, evaluating M in combination with platinum (P), etoposide (E), and durvalumab (D) in patients (pts) with previously untreated ES-SCLC. Addition of M to first-line EP + D led to no new severe AEs in patients with ES-SCLC. Estimated 1-yr PFS was not statistically superior to historical control with EP +D, yet a subset of patients including those with baseline brain metastasis derived durable benefit. Long term follow-up and biomarker analysis are ongoing."

Clinical • Acute Kidney Injury • CNS Disorders • Endocrine Disorders • Lung Cancer • Nephrology • Oncology • Renal Disease • Small Cell Lung Cancer • Solid Tumor • CD8 • KLRC1