evorpacept (ALX148) / ALX Oncology - LARVOL DELTA

Final results of a phase I trial of evorpacept (ALX148), lenalidomide, and rituximab for patients with B-cell non-Hodgkin lymphoma (AACR 2025) - P1/2 | "The combination of evorpacept and R2 has a safe toxicity profile, promising anti-tumoral activity (historical CR rate 30%), and induces favorable biological effects on multiple components of the tumoral immune microenvironment. A phase 2 study investigating its efficacy in pts with previously untreated and high tumor burden iNHL has completed enrollment."

Clinical • Late-breaking abstract • P1 data • B Cell Non-Hodgkin Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • SIRPA

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

PRE-I-SPY-PI: PRE-ISPY Phase I/II Oncology Platform Program (clinicaltrials.gov) - P1/2 | N=280 | Recruiting | Sponsor: QuantumLeap Healthcare Collaborative | Phase classification: P1 ➔ P1/2 | N=124 ➔ 280 | Trial completion date: Dec 2029 ➔ Dec 2031 | Trial primary completion date: Dec 2028 ➔ Dec 2030

Biomarker • Enrollment change • Phase classification • Trial completion date • Trial primary completion date • Breast Cancer • Cholangiocarcinoma • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

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

­­­­­­Evorpacept plus enfortumab vedotin in patients (Pts) with locally advanced or metastatic urothelial carcinoma (la/mUC): Phase 1a dose escalation results. (ASCO 2024) - P1 | "This is the first study, to our knowledge, reporting data on the combination of a CD47 blocking agent in combination with an ADC in la/mUC. EVO plus EV is well tolerated at doses evaluated with no MTD reached and a MAD of 30 mg/kg Q2W. The combination shows early promising clinical activity compared to an ORR of 41% with EV alone in pts with la/mUC who had previously received platinum-based chemotherapy and a PD-1/L1 inhibitor (Powles et al."

Clinical • Metastases • P1 data • Constipation • Diabetes • Fatigue • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Nephrology • Oncology • Pain • Solid Tumor • Urothelial Cancer • SIRPA

Final analysis of the randomized phase 2 part of the ASPEN-06 study: A phase 2/3 study of evorpacept (ALX148), a CD47 myeloid checkpoint inhibitor, in patients with HER2-overexpressing gastric/gastroesophageal cancer (GC). (ASCO-GI 2025) - P2/3 | " The ASPEN-06 randomized phase 2 trial evaluates Evo in combination with standard trastuzumab (T), ramucirumab (R) and paclitaxel (P) for the treatment of patients with HER2+ GC. The addition of Evo to TRP showed promising activities in HER2+ GC. The magnitude of response was greatest in tumors identified as HER2+ using fresh biopsies emphasizing the importance of biopsies post anti HER2 therapy. Consistent with Evo's mechanism of enhancing antibody dependent phagocytosis, these data support its ongoing investigation as an adjunct to anti-HER2 gastric cancer therapy."

Checkpoint inhibition • Clinical • P2/3 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

A phase I investigator-initiated trial of evorpacept (ALX148), lenalidomide and rituximab for patients with relapsed or refractory B-cell non-Hodgkin lymphoma (AACR 2024) - P1/2 | "Bulk RNA sequencing and multiplex immunofluorescence are being performed on tissue biopsies collected before and during treatment, to characterize its effects on the tumor immune microenvironment. A phase 2 study investigating its efficacy in pts with previously untreated iNHL is now enrolling."

Clinical • P1 data • B Cell Non-Hodgkin Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • SIRPA

Exploratory biomarker analysis from a phase Ib/II trial of zanidatamab (zani) + evorpacept (evo) in patients (pts) with HER2+ metastatic breast cancer (mBC) (ESMO-BC 2026) - P1/2 | "Funding: Jazz Pharmaceuticals in collaboration with ALX Oncology Inc. Responses to zani + evo with ccHER2+ mBC were largely restricted to pts with higher CD47 expression, supporting a CD47-dependent, HER2-driven biology. Most ccHER2+ pts remained ERBB2-amplified post–T-DXd, supporting use of HER2-targeted therapy, including zani, after progression. Also, on-treatment ERBB2 CN and ctDNA reductions and fewer alterations in RTK signaling pathways support HER2-driven signaling with minimal compensatory pathway activation."

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

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

Beyond immune checkpoint blockade: T cell engagers and antibody-drug conjugates in cancer and autoimmune disease. (PubMed, Biochem Pharmacol) - "The CD47/SIRPα innate immune checkpoint is briefly examined as a case study in next-generation immunopharmacology, with agents like evorpacept and BYON4228 showing encouraging objective response rates (50% ORR) in non-hodgkin lymphoma when combined with rituximab, with next-generation designs reducing hematologic toxicity. Recent compassionate use findings in autoimmunity demonstrate that CD19 × CD3 TCE (blinatumomab) and (B-cell maturation antigen) BCMA × CD3 TCE (teclistamab) elicit rapid clinical improvement in refractory antisynthetase syndrome and systemic sclerosis, accompanied by cytokine release syndrome (CRS) (grade 3 in 40% and 100% of patients, respectively) and no neurotoxicity...Conversely, ADC strategies have yielded mixed results; an anti-TNF-glucocorticoid receptor modulator ADC failed to outperform adalimumab in a phase 2b trial. Safety profiles differ: TCEs predominantly cause cytokine release syndrome, whereas ADCs pose off-target payload..."

Checkpoint inhibition • Journal • Review • Dermatology • Hematological Disorders • Hematological Malignancies • Hidradenitis Suppurativa • Immunology • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Rare Diseases • Rheumatology • Scleroderma • Systemic Sclerosis • SIRPA • TNFSF4

ALX Oncology Q2 2026 Highlights and Recent Developments (Yahoo Finance) - "Enrollment in the ongoing ASPEN-09-Breast Phase 2 trial evaluating evorpacept in combination with trastuzumab remains on track, with topline data from 80 patients expected in mid-2027....Enrollment continues in the dose-escalation portion of the Phase 1 trial of ALX2004, a novel antibody-drug conjugate (ADC) for the treatment of epidermal growth factor receptor (EGFR)-expressing solid tumors, and is on track to report safety data in the second half of 2026."

P1 data • P2 data • Trial status • Colorectal Cancer • Esophageal Squamous Cell Carcinoma • HER2 Positive Breast Cancer • Non Small Cell Lung Cancer • Squamous Cell Carcinoma of Head and Neck

Study of Evorpacept (ALX148) With Cetuximab and Pembrolizumab for Refractory Microsatellite Stable Metastatic Colorectal Cancer (clinicaltrials.gov) - P2 | N=19 | Terminated | Sponsor: University of Colorado, Denver | N=48 ➔ 19 | Active, not recruiting ➔ Terminated; Accrual was terminated due to safety concerns

Enrollment change • Trial termination • Colorectal Cancer • Oncology • Solid Tumor

Safety and Efficacy of Anti-CD47, ALX148 in Combination With Liposomal Doxorubicin and Pembrolizumab in Recurrent Platinum-resistant Ovarian Cancer (clinicaltrials.gov) - P2 | N=16 | Active, not recruiting | Sponsor: Alexander B Olawaiye, MD | Trial completion date: Jan 2031 ➔ Apr 2029

Platinum resistant • Trial completion date • Oncology • Ovarian Cancer • Solid Tumor

Neoadjuvant Immunoradiotherapy With Evorpacept and Pembrolizumab in HPVOPC (Human Papilloma Virus Oropharynx Cancer) (clinicaltrials.gov) - P2 | N=28 | Active, not recruiting | Sponsor: University of California, San Diego | Trial completion date: May 2028 ➔ Oct 2029

Trial completion date • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor

Mechanisms of resistance to macrophage checkpoint inhibitors in B-cell non-Hodgkin lymphoma for the British Journal of Haematology. (PubMed, Br J Haematol) - No abstract available

Checkpoint inhibition • Journal • B Cell Non-Hodgkin Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

ASPEN-09-03: A Study of Evorpacept in Combination With Trastuzumab and Chemotherapy in Metastatic HER2-Positive Breast Cancer (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: ALX Oncology Inc.

Trial initiation date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Neoadjuvant Immunoradiotherapy With Evorpacept and Pembrolizumab in HPVOPC (Human Papilloma Virus Oropharynx Cancer) (clinicaltrials.gov) - P2 | N=29 | Active, not recruiting | Sponsor: University of California, San Diego | Recruiting ➔ Active, not recruiting

Enrollment closed • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor

Upcoming Clinical Milestones (GlobeNewswire) - "Phase 2 ASPEN-09-Breast trial: Topline data readout for 80 patients anticipated in mid-2027. Phase 1 ALX2004 trial: Safety data from the dose-escalation phase of the trial anticipated in 2H 2026."

P1 data • P2 data • Colorectal Cancer • Esophageal Squamous Cell Carcinoma • HER2 Positive Breast Cancer • Non Small Cell Lung Cancer • Squamous Cell Carcinoma of Head and Neck

ALX Oncology’s Evorpacept in Combination with Zanidatamab Generates Promising, Durable Response in Patients with Advanced HER2-Positive Breast Cancer and High CD47 Expression (The Manila Times) - "ALX Oncology will host a webcast on May 8 to report first quarter 2026 financial results; breast cancer expert will discuss the evorpacept + zanidatamab trial results in detailt...The cORR among all 24 patients was 33% and the mPFS was 3.6 months; Patients with ccHER2-positive disease (n=10) had higher response rates, with a cORR of 60% and mPFS of 8.3 months; All of the patients (n=5/5) with ccHER2-positive disease and high CD47 defined as total membrane staining of >20%) responded (including one complete response and four partial responses), with an mDOR of 20.2 months and mPFS of 22.1 months."

Biomarker • P1/2 data • HER2 Positive Breast Cancer

ALX Oncology Announces That CD47 Biomarker Data from Clinical Trial Evaluating Evorpacept + Zanidatamab Combination in Advanced Breast Cancer Will Be Presented at ESMO Breast Cancer 2026 (GlobeNewswire) - "The ESMO Breast Cancer poster presentation will highlight data from exploratory analyses conducted to identify biomarkers predictive of response to the evorpacept + zanidatamab regimen...The Company also announced it will report first quarter 2026 financial results on Friday, May 8, 2026, before market open."

P1/2 data • HER2 Positive Breast Cancer

Phase 1 study of azacitidine in combination with evorpacept for higher-risk myelodysplastic syndrome (MDS) (AACR 2024) - P1 | "The myeloid checkpoint inhibitor EVO was well tolerated in combination with AZA with an initial safety and activity profile comparable to that of historical AZA monotherapy. Additional updated data will be provided at the time of presentation."

Combination therapy • P1 data • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • TP53

ASPEN-09-03: A Study of Evorpacept in Combination With Trastuzumab and Chemotherapy in Metastatic HER2-Positive Breast Cancer (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: ALX Oncology Inc. | Phase classification: P1/2 ➔ P2 | N=80 ➔ 120 | Trial completion date: Dec 2027 ➔ Dec 2028 | Trial primary completion date: Jun 2027 ➔ Dec 2027

Enrollment change • Phase classification • Trial completion date • Trial initiation date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Zanidatamab, a Dual HER2-Targeted Bispecific Antibody, in Patients With Unresectable Locally Advanced or Metastatic HER2-Positive Salivary Gland Cancer: A Combined Analysis of Early-Phase Studies. (PubMed, Clin Cancer Res) - P=N/A, P1, P1/2 | "Although the sample size is small, these findings support the clinical benefit of zanidatamab treatment for HER2-positive SGC."

First-in-human • Journal • Oncology • Salivary Gland Cancer • HER-2

ALX148, Rituximab and Lenalidomide for the Treatment of Indolent and Aggressive B-cell Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1/2 | N=47 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial primary completion date: Mar 2026 ➔ Mar 2028 | Trial completion date: Mar 2026 ➔ Mar 2028

Trial completion date • Trial primary completion date • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Indolent Lymphoma • Large B Cell Lymphoma • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Mediastinal Large B-Cell Lymphoma • Richter's Syndrome

AT148009: A Study of Evorpacept (ALX148) in Patients with Metastatic HER2-Positive Breast Cancer (clinicaltrialsregister.eu) - P1/2 | N=36 | Not yet recruiting | Sponsor: Alx Oncology Holdings Inc.

New P1/2 trial • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2