On October 3, 2023 ALX Oncology Holdings Inc., ("ALX Oncology" or the "Company") (Nasdaq: ALXO), an immuno-oncology company developing therapies that block the CD47 immune checkpoint pathway, reported positive prespecified interim Phase 2 data from its ASPEN-06 clinical trial, a randomized multi-center international study evaluating evorpacept, the Company’s CD47 blocking therapeutic, in combination with trastuzumab, CYRAMZA (ramucirumab) and paclitaxel for the treatment of patients with HER2-positive gastric/gastroesophageal junction ("GEJ") cancer (Press release, ALX Oncology, OCT 3, 2023, View Source [SID1234635589]). This prespecified interim analysis represents results from 54 randomized patients with second and third line gastric/GEJ cancer, including a meaningful number of patients previously treated with ENHERTU (trastuzumab deruxtecan) and checkpoint inhibitors. Patients were treated with evorpacept at 30 mg/kg every two weeks, mirroring the treatment cycle of trastuzumab, CYRAMZA and paclitaxel.
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Phase 2 ASPEN-06 Interim Analysis Results:
A confirmed overall response rate ("ORR") of 52% was demonstrated for evorpacept in combination with trastuzumab + CYRAMZA + paclitaxel compared to 22% for the control group of trastuzumab + CYRAMZA + paclitaxel.
Median duration of response ("mDOR") was not reached for the evorpacept combination treatment arm compared to 7.4 months for the control group.
The safety profile of evorpacept was consistent with previous clinical trials and was well-tolerated.
These interim results compare favorably to the efficacy reported for CYRAMZA + paclitaxel in the RAINBOW study (ORR of 28% and mDOR of 4.4 months), which is the regulatory benchmark and global standard of care for second line gastric/GEJ cancer.
"The ASPEN-06 clinical trial validates the potential of evorpacept both in solid tumors and in combination with anti-cancer antibodies and these data highlight the drug’s potential as a first-in-class foundational immunotherapy," said Sophia Randolph, M.D., Ph.D., Chief Medical Officer, ALX Oncology. "We are highly encouraged by these initial randomized efficacy and safety results in gastric cancer that build upon the activity previously seen in our first-in-human study and represent the first positive randomized clinical trial data presented for any CD47 blocker. In addition, ASPEN-06 is the first global randomized study in HER2-positive gastric cancer where prior KEYTRUDA (pembrolizumab) and ENHERTU were allowed. We look forward to reporting the final analysis from the ongoing Phase 2 ASPEN-06 study in Q2 2024 and plan to initiate the Phase 3 portion of ASPEN-06 in late 2024."
"These data in gastric cancer represent the first positive initial result in a randomized trial setting of blocking the CD47 immune checkpoint pathway with a CD47 blocker that has an inactive Fc effector function in order to treat patients living with advanced gastric cancer," said Keun Wook Lee, M.D., Ph.D., Professor at Seoul National University College of Medicine and ASPEN-06 Principal Investigator. "Patients with advanced disease face poor outcomes following progression on initial treatment with HER2-directed therapy. Evorpacept could represent a breakthrough in therapy and a potential paradigm shift in the gastric cancer care continuum."
Upcoming Clinical Milestones for Evorpacept’s Development Pipeline
1H 2024
Non-Hodgkin Lymphoma – Phase 1b investigator-sponsored trial with rituximab + lenalidomide top line results (Q1/Q2 2024)
Gastric/GEJ Cancer – Phase 2 ASPEN-06 randomized top line final results (Q2 2024)
2H 2024
Head and Neck Squamous Cell Carcinoma – Phase 2 ASPEN-03 with KEYTRUDA randomized top line results
Head and Neck Squamous Cell Carcinoma – Phase 2 ASPEN-04 with KEYTRUDA + chemotherapy randomized top line results
Gastric/GEJ Cancer – Phase 3 ASPEN-06 study initiation
Urothelial Carcinoma – Phase 1b ASPEN-07 with PADCEV (enfortumab vedotin-ejfv) top line results
Breast Cancer – Phase 1b I-SPY study with ENHERTU top line results
Conference Call on October 3 at 8:00 am EDT
The Company will host a conference call and webcast today at 8:00 AM EDT that will feature ASPEN-06 investigator Dr. Josep Tabernero, Director of the Vall d’Hebron Institute of Oncology and Head of the Medical Oncology Department at the Vall d’Hebron University Hospital in Barcelona, Spain and past President of the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper).
To access the live conference call, please dial (800) 715-9871 (U.S./Canada) or +44.800.260.6466 (internationally) at least 10 minutes prior to the start time and refer to conference ID 7797378. The link to the live webcast of the conference call will be posted in the News & Events section (see "Events") of the Company’s website at www.alxoncology.com. An archived replay will be accessible for 90 days following the event.
About the ASPEN-06 Study
ASPEN-06 is a randomized Phase 2 (open-label) / Phase 3 (double-blinded), multi-center international study of patients with second or third line metastatic HER2-overexpressing gastric/GEJ adenocarcinoma that has progressed on or after prior HER2-directed therapy and fluoropyrimidine- or platinum-containing chemotherapy. While trastuzumab is currently approved in combination with cisplatin or capecitabine for HER2-positive gastric/GEJ cancers, it is not yet approved with the standard-of-care of CYRAMZA + paclitaxel. The Phase 2 portion of the ASPEN-06 study is designed to enroll 122 patients who have progressed on, or after prior HER2-directed therapy and fluoropyrimidine and/or platinum-containing regimens. To determine the activity of evorpacept + trastuzumab + CYRAMZA + paclitaxel, in the Phase 2 portion of ASPEN-06, patients are randomized to receive either a four-drug combination regimen (evorpacept + trastuzumab + CYRAMZA + paclitaxel) or a three-drug combination regimen (trastuzumab + CYRAMZA + paclitaxel). This design enables the assessment of evorpacept’s contribution to the standard of care plus trastuzumab and to global standard of care, CYRAMZA + paclitaxel. Should the Phase 2 portion of the trial demonstrate proof of concept, the trial will progress to the Phase 3 portion where the evorpacept containing four-drug regimen will be tested against the two-drug global standard of care of CYRAMZA + paclitaxel.
About Gastric Cancer and Gastroesophageal Junction Cancer
Gastric cancer ("GC") begins in the cells lining the inner wall of the stomach and spreads through the outer layers and eventually the body as it grows. GC is the fifth most common cancer worldwide and the third leading cause of cancer mortality as reported by GLOBOCAN. The American Cancer Society estimates there will be 26,500 newly diagnosed cases of GC at all stages in the U.S. in 2023, and approximately 17 percent of all GC patients have HER2-positive disease. The five-year survival rate is only 5.5 percent for those patients diagnosed with metastatic disease. GC is more common in East Asian countries, with incidence rates 4 to 10 times higher than in the U.S.