evorpacept (ALX148) / ALX Oncology - LARVOL DELTA

A phase II investigator-initiated frontline trial of evorpacept (ALX148), lenalidomide and rituximab for high tumor burden indolent b-cell non-Hodgkin lymphoma (ASH 2025) - P1/2 | "The addition of evorpacept to R2 is a safe and effective frontline non-chemotherapyregimen for iNHL patients, resulting in high CR rates. While longer follow-up matures, serial bloodsamples are being evaluated for circulating tumor DNA by phased variant enrichment and detectionsequencing (PhasED-seq) to determine the minimal residual disease eradication rate with this novelregimen."

P2 data • B Cell Non-Hodgkin Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Infectious Disease • Lymphoma • Marginal Zone Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • SIRPA

Pre-ispy trial: a phase i/ib oncology platform program (pre-i-spy-p1) nct05868226 (SABCS 2025) - P1 | "The current arms under study are PRE1 ALX-148/T-DXd; PRE2 tucatinib/zanidatamab; and PRE3 vidutolimod/cemiplimab. Conclusion The PRE-ISPY phase I/Ib trial has been successfully implemented nationally as part of the Consortium of I-SPY trials. Once safety is established, promising regimens can be rapidly transitioned to I-SPY2.2, K-SPY or other phase II/III trials."

P1 data • Breast Cancer

Evorpacept (ALX-148) combined with trastuzumab deruxtecan in patients with HER2 positive/HER2low metastatic breast cancer (mBC): results from the PRE-ISPY phase Ib trial (SABCS 2025) - P1 | "Conclusions In this phase I study, Evo + T-DXd demonstrated a manageable safety profile comparable with T-DXd alone and evidence of antitumor activity in pretreated HER2+/HER2low mBC. There were no new safety signals."

Clinical • Metastases • P1 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CD47 • HER-2

ALX Oncology Announces Positive Results from Ongoing Investigator-Sponsored Phase 2 Trial Evaluating Evorpacept in Combination with Standard-of-Care Treatment in Patients with Indolent B-cell Non-Hodgkin Lymphoma, at ASH Annual Meeting (GlobeNewswire) - "The primary objective of best CR rate above 80% was met with evorpacept added to R2 in the context of a historical R2 CR rate of 50%. The investigators found the addition of evorpacept to R2 to be a well-tolerated frontline non-chemotherapy regimen for patients with iNHL, resulting in a high CR rate. 92% of patients achieved a complete response, and 8% achieved a partial response (PR), with the overall response rate (ORR) being 100%. One year progression free survival (PFS) rate was 91%, and one year overall survival (OS) rate was 100%."

P2 data • B Cell Non-Hodgkin Lymphoma • Follicular Lymphoma • Indolent Lymphoma • Marginal Zone Lymphoma

Single-Cell Genomics and Proteomics Reveals Venetoclax-Resistant Monocytic Differentiation of TP53 LOH Clones in TP53 Mutant AML (ASH 2023) - " Patients 1 and 3 received treatment with CD47AB (Magrolimab), 5'-Azacitidine (Aza), and Venetoclax (Ven); Patient 2 received IMGN632 (CD123-targeting ADC), Aza and Ven. Patient 4 received p97 Inhibitor CB-5339; Patient 5 received CD47 inhibitor (ALX148), Aza, Ven... This study establishes a genotype-phenotype connection through single-cell proteogenomic profiling of TP53-mutated AML, describing the clonal evolution and immunophenotypic dynamics during treatment while proposing a potential mechanism of resistance."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2L1 • CD123 • CD14 • CD33 • CD34 • CD36 • CD68 • CD8 • EIF4EBP1 • ETV6 • IDH1 • IL3RA • ITGAM • KIT • SCARB1 • TP53

The Phase 2 ASPEN-09-Breast Cancer clinical trial of evorpacept plus trastuzumab and physician’s choice chemotherapy in patients with HER2+ breast cancer previously treated with ENHERTU (fam-trastuzumab deruxtecan-nxki) is on track to begin enrollment in Q4 2025, with interim data expected in Q3 2026. (The Manila Times)

Enrollment status • P2 data • HER2 Positive Breast Cancer

In a pre-planned exploratory analysis of the ASPEN-06 clinical trial in gastric cancer, CD47 overexpression was identified as a key predictive biomarker for response and durable benefit in patients with retained HER2 expression. (The Manila Times) - "In patients with retained HER2+ and CD47-high gastric cancer (n=43), evorpacept + HERCEPTIN (trastuzumab), CYRAMZA (ramucirumab) and paclitaxel (TRP) had a 65.0% objective response rate (ORR) versus 26.1% ORR for TRP, while patients with HER2+ and CD47-low gastric cancer (n=47), evorpacept + TRP had a 37.5% ORR compared to 26.1% ORR for TRP."

P2 data • Gastric Cancer

CD47 expression as a predictive biomarker for evorpacept in HER2-positive gastric/gastroesophageal cancer from the Phase 2 randomized ASPEN-06 trial (SITC 2025) - "Previously, evo has demonstrated improved objective response, duration of response, and PFS in combination with trastuzumab (T), ramucirumab (R), and paclitaxel (P) in advanced, previously treated HER2+ gastric/gastroesophageal cancer (GC) in ASPEN-06.1Methods The ASPEN-06 randomized phase 2 trial assessed evo (30 mg/kq Q2W) + TRP vs. TRP in patients with 2nd or 3rd line HER2+ advanced or metastatic GC that had progressed on or after prior anti-HER2 therapy. Further evaluation of the potential for patient selection by CD47 for evo-based combinations in GC and other indications is warranted.Trial Registration ClinicalTrials.gov identifier NCT05002127Ethics Approval The study was conducted in accordance with all relevant local/national regulatory requirements, the International Ethical Guidelines for Biomedical Research Involving Human Subjects and the Declaration of Helsinki. All research was approved by the relevant institutional review boards or ethics committees, and..."

Biomarker • Clinical • P2 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Oncology • Solid Tumor • CD47 • HER-2

Biological Mechanisms of Resistance to Macrophage Checkpoint Inhibitors in Relapsed B-cell Non-Hodgkin Lymphoma (SITC 2025) - P1/2 | "We have previously demonstrated that evorpacept (ALX148), a high-affinity CD47 blocker with an inert Fc region, can induce durable remissions when combined with rituximab and lenalidomide (R2).1 We present here a detailed biological characterization of patients who progressed on this novel macrophage checkpoint inhibitor.Methods In this single-arm phase 1 trial (NCT05025800), adult patients with relapsed indolent B-NHL received evorpacept in combination with R2 for 12 cycles. No sub-clonal mutations were observed.Conclusions Genetic pathways relevant to lipid metabolism and epigenetics, at the interface between innate and adaptive immunity, may mediate resistance to macrophage checkpoint inhibitors. Functional in vitro and in vivo validation of these findings is ongoing and may help enhance the activity of these agents for the treatment of B-NHL."

Checkpoint inhibition • IO biomarker • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • B2M • BCL2 • CD8 • CREBBP • CST3 • ITGAX • KMT2D • PSME1 • SAT1

ASPEN-04: A randomized phase II study of evorpacept in combination with pembrolizumab and chemotherapy in patients with recurrent, unresectable or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) (ESMO 2025) - P2 | "Methods ASPEN-04 is a randomized, open-label Phase 2 study evaluating evo in combination with P and C [5FU + either carboplatin or cisplatin] in patients with previously untreated, R/M HNSCC...Conclusions The addition of evo to PC did not meet the primary endpoint of improved ORR in R/M HNSCC as compared to historical control. While additional exploratory analyses are ongoing, study results do not support further development of evo in combination with PC in R/M HNSCC."

Clinical • Combination therapy • Metastases • P2 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

ASPEN-03: A randomized phase II study of evorpacept in combination with pembrolizumab in patients with recurrent, unresectable or metastatic (R/M) PD-L1 positive head and neck squamous cell carcinoma (HNSCC) (ESMO 2025) - P2 | "DOR, PFS, OS, and the results of exploratory analyses will be presented at the meeting. Conclusions The addition of evo to P was well-tolerated, but did not meet the primary endpoint of improving ORR in PD-L1-positive R/M HNSCC as compared to historical control."

Clinical • Combination therapy • Metastases • P2 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

Phase II clinical trial and preclinical evaluation of a novel CD47 blockade combination in refractory microsatellite stable metastatic colorectal cancer. (PubMed, Cancer Res Commun) - "Introduction In this preclinical human immune system patient-derived xenograft (HIS PDX) model and phase II clinical trial, we assessed evorpacept (anti-CD47 engineered fusion protein with inactive Fc), cetuximab, and pembrolizumab (triple therapy) in microsatellite stable colorectal cancer (MSS CRC). Conclusions While triple therapy demonstrated evidence of efficacy in refractory MSS CRC, safety concerns halted enrollment. Further investigation is necessary to determine the optimal use of CD47-targeted therapies in MSS CRC."

Journal • P2 data • Preclinical • Colorectal Cancer • Hemophagocytic lymphohistiocytosis • Immunology • Oncology • Rare Diseases • Solid Tumor • CD8

A Study of Evorpacept (ALX148) in Patients With Advanced Solid Tumors and Lymphoma (ASPEN-01) (clinicaltrials.gov) - P1 | N=174 | Completed | Sponsor: ALX Oncology Inc. | Trial completion date: Dec 2024 ➔ Jul 2025 | Active, not recruiting ➔ Completed

Trial completion • Trial completion date • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

A single-arm phase 2 study of evorpacept in combination with trastuzumab and chemotherapy in participants with HER2-positive metastatic breast cancer (mBC) (ASPEN-09-03) (ESMO 2025) - "In 2L+ HER2+ gastric cancer patients, the addition of evo to trastuzumab-ramucirumab-paclitaxel (TRP) demonstrated an objective response rate (ORR) of 41.3% and duration of response (DoR) of 15.7mos compared to the TRP control, ORR 26.6% and DoR 9.1mos (N=127) per investigator assessment (IA)...In a phase 1b study, evo plus zanidatamab (HER2 bispecific antibody) showed promising activity in heavily pretreated patients with centrally confirmed HER2-positive mBC, ORR 55.6%; progression-free survival (PFS) 7.4mos...Trial design The ASPEN-09-03 study is a phase 2 single arm global study evaluating evo in combination with Tras and single agent chemotherapy of physician's choice (vinorelbine, capecitabine, gemcitabine, paclitaxel, or eribulin) in patients with HER2+ mBC previously treated with T-DXd...The primary endpoint in this trial is ORR by independent central review. Key secondary endpoints include ORR by IA, clinical benefit rate, DoR, PFS, overall survival, and..."

Combination therapy • Metastases • P2 data • Breast Cancer • Gastric Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • SIRPA

HCB101: a novel potent ligand-trap Fc-fusion protein targeting the CD47-SIRPα pathway with high safety and preclinical efficacy for hematological and solid tumors. (PubMed, J Hematol Oncol) - "HCB101 demonstrates high-affinity binding to CD47, robustly promotes macrophage-mediated phagocytosis of tumor cells without affecting red blood cells and exhibits unique advantages over current CD47-targeting agents, including Hu5F9-G4, TTI-622, and ALX148. Additionally, HCB101 treatment increased the M1/M2 macrophage ratio in the tumor microenvironment, suggesting repolarization of tumor-associated macrophages (TAMs) toward a pro-inflammatory phenotype. No dose-limiting toxicities or hematologic adverse effects were observed in murine or non-human primate studies."

IO biomarker • Journal • Preclinical • Hematological Disorders • Oncology • Solid Tumor • CD47 • SIRPA

Zanidatamab in patients with advanced HER2-positive salivary gland cancer: A pooled analysis of early-phase studies (AACR-NCI-EORTC 2025) - P=N/A, P1, P1/2, P2 | "Five (56%) had prior HER2-targeted therapy (trastuzumab, n = 3; pertuzumab + trastuzumab, n = 2), the median (range) age was 68 (52–75) years, and most pts (7 [78%]) were male...One pt who had prior HER2-targeted therapy received zanidatamab + evorpacept (study ZW25-204) and had a confirmed PR. Zanidatamab was well tolerated and showed preliminary antitumor activity in pts with HER2+ advanced SGC. Although the sample size is small, these findings reinforce HER2 as an actionable target in SGC and support further evaluation of zanidatamab in SGC in the ongoing DiscovHER PAN-206 trial (NCT06695845)."

Late-breaking abstract • Metastases • Retrospective data • Biliary Cancer • Biliary Tract Cancer • Oncology • Salivary Gland Cancer • HER-2

ZWI-ZW25-204: A Study of Zanidatamab (ZW25) With Evorpacept (ALX148) in Patients With Advanced HER2-expressing Cancer (clinicaltrials.gov) - P1/2 | N=52 | Completed | Sponsor: Jazz Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Breast Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology

ALX Oncology to Present Updated Data from Phase 2 ASPEN-06 Trial, Highlighting CD47 Expression as a Predictive Biomarker in HER2+ Gastric Cancer, at 40th Society for Immunotherapy of Cancer (SITC) Annual Meeting (GlobeNewswire) - "The Phase 2 trial evaluated evorpacept, the Company’s lead therapeutic candidate, in combination with HERCEPTIN (trastuzumab), CYRAMZA (ramucirumab) and paclitaxel, for patients with previously treated HER2-positive advanced gastric cancer (GC) and gastroesophageal junction (GEJ) cancer."

Biomarker • P2 data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma

ASPEN-09: A Study of Evorpacept in Combination With Anti-cancer Therapies in Advanced / Metastatic Malignancies (clinicaltrials.gov) - P1/2 | N=80 | Recruiting | Sponsor: ALX Oncology Inc. | N=280 ➔ 80

Enrollment change • Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

A Study of Evorpacept (ALX148) in Patients With Advanced HER2+ Gastric Cancer (ASPEN-06) (clinicaltrials.gov) - P2/3 | N=127 | Active, not recruiting | Sponsor: ALX Oncology Inc. | N=450 ➔ 127 | Trial completion date: Aug 2028 ➔ Jun 2026

Enrollment change • Trial completion date • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • HER-2

ALX Oncology Reports Second Quarter 2025 Financial Results and Provides Corporate Update (GlobeNewswire) - "Data from ASPEN-06 trial...to be presented at a medical conference in Q4 2025....Upcoming Clinical Milestones: ASPEN-Breast Cancer: Patient dosing anticipated to begin in Q4 2025 based on updated protocol. Interim data from this trial anticipated in Q3 2026."

Clinical data • New trial • Gastric Cancer • HER2 Positive Breast Cancer

Evorpacept (ALX148) in Combination With Pembrolizumab in Patients With Advanced Head and Neck Squamous Cell Carcinoma (ASPEN-03) (clinicaltrials.gov) - P2 | N=189 | Active, not recruiting | Sponsor: ALX Oncology Inc. | Trial completion date: Dec 2025 ➔ Jun 2026 | Trial primary completion date: Jun 2025 ➔ Mar 2025

Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

Evorpacept (ALX148) in Combination With Pembrolizumab and Chemotherapy in Patients With Advanced Head and Neck Squamous Cell Carcinoma (ASPEN-04) (clinicaltrials.gov) - P2 | N=172 | Active, not recruiting | Sponsor: ALX Oncology Inc. | Trial completion date: Dec 2025 ➔ Jun 2026 | Trial primary completion date: Jun 2025 ➔ Mar 2025

Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

A Phase I Trial of Evorpacept, Lenalidomide and Rituximab for Patients with B-cell Non-Hodgkin Lymphoma. (PubMed, Clin Cancer Res) - P1/2 | "ER2 has a safe toxicity profile, promising anti-tumoral activity, and induces favorable biological effects on the tumoral immune microenvironment."

Journal • P1 data • B Cell Non-Hodgkin Lymphoma • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • SIRPA

A Study of Evorpacept (ALX148) With Enfortumab Vedotin for Subjects With Urothelial Carcinoma (ASPEN-07) (clinicaltrials.gov) - P1 | N=36 | Completed | Sponsor: ALX Oncology Inc. | Active, not recruiting ➔ Completed

Trial completion • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer