Evorpacept in combinatie met Zanidatamab geeft uitstekende resultaten bij patiënten met gevorderde voorbehandelde HER2-positieve borstkanker met hoge CD47expressie

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14 augustus 2026: Bron: persbericht van ALX Oncology

Immuuntherapie met Evorpacept in combinatie met Zanidatamab geeft langdurige remissies bij zwaar voorbehandelde patiënten met gevorderde HER2-positieve borstkanker met een hoge CD47-expressie ook wel het 'eet-me-niet-op'-signaal genoemd. Concreet hadden patiënten in de studie met HER2-positieve borstkanker en een hoge CD47-expressie een bevestigde complete remissie van 100% bij alle 5 patiënten (n=5/5), in vergelijking met 25 % (n=1/4) bij patiënten met een lagere CD47-expressie.
Patiënten met tumoren met hogere waarden van CD47-expressie, hadden ook een langere mediane ziekteprogressievrije overleving: 22,1 maanden vergeleken met 3,4 maanden in de groep met lage CD47-expressie. De mediane duur van de remissie bij patiënten van wie de tumoren hoge niveaus van CD47 tot expressie brachten, was 20,2 maanden. Daarbij opgemerkt dat de deelnemende patiënten minimaal 5 eerdere behandelingen hadden gehad op de Her2-positieve expressie en eerst werden geselecteerd en ingedeeld op hoge en lage CD47-expressie.

Zo blijkt uit een update van de nieuwe studiegegevens van deze gerandomiseerde fase Ib/II studie volgens een persbericht van de producent van Evorpacept. Zij verwijzen daarbij naar deze poster die 30 april 2026 werd gepresenteerd op ESMO 2026. Eerder werden resultaten gepresenteerd in 2025 zie abstract verderop in dit artikel.

Hier het persbericht van de producent waaruit bovenstaande tekst is gehaald en vertaald, daaronder het abstract:

ALX Oncology’s Evorpacept in Combination with Zanidatamab Generates Promising, Durable Response in Patients with Advanced HER2-Positive Breast Cancer and High CD47 Expression

May 7, 2026

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- Data from Phase 1b/2 trial presented at ESMO Breast Cancer 2026 further validate a biomarker-driven development strategy for evorpacept -

- Findings are consistent with previous results from the randomized ASPEN-06 trial in HER2-positive gastric cancer, which indicated CD47 expression could potentially serve as an important predictive biomarker of evorpacept activity -

- 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 detail -

SOUTH SAN FRANCISCO, Calif., May 07, 2026 (GLOBE NEWSWIRE) -- ALX Oncology Holdings Inc. ("ALX Oncology" Nasdaq: ALXO), a clinical-stage biotechnology company advancing a pipeline of novel therapies designed to treat cancer and extend patients’ lives, announced that data from exploratory analyses in the Phase 1b/2 clinical trial evaluating the company’s investigational CD47-inhibitor evorpacept in combination with Jazz Pharmaceuticals’ zanidatamab (ZIIHERA®) in patients with heavily pre-treated HER2-positive metastatic breast cancer (mBC) were presented for the first time today in a poster session at the ESMO Breast Cancer 2026 congress. The findings show that patients with centrally confirmed HER2-positive (ccHER2-positive) mBC and high CD47 expression experienced a promising, durable response.

Specifically, patients in the trial with ccHER2-positive disease and high CD47 expression (defined as total membrane staining of >20%) had a confirmed objective response rate (cORR) of 100% (n=5/5), while the cORR was 25% (n=1/4) among those with lower CD47 expression (<20%). Those patients whose tumors expressed higher levels of CD47 also had longer median progression-free survival (mPFS): 22.1 months as compared to 3.4 months in the low-CD47 expression group. The median duration of response (mDOR) among patients whose tumors expressed high levels of CD47 was also notable at 20.2 months.

"There is a large and growing population of patients with advanced breast cancer who need novel treatment options once their disease has progressed following treatment with currently available therapies, including trastuzumab deruxtecan," said Funda Meric-Bernstam, M.D., Chair of the Department of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center, who presented the findings today. "Our data suggest that adding evorpacept to HER2-targeted agents may provide one such option, and we may be able to optimize patient selection for these regimens by using a biomarker-driven approach that incorporates CD47."

The Phase 1b/2 open-label, multi-center clinical trial (NCT05027139) evaluating evorpacept plus zanidatamab included patients with heavily pre-treated HER2-positive mBC (median of five prior HER2-targeted therapies), all of whom had received prior ENHERTU therapy. The primary trial results, presented at the 2024 San Antonio Breast Cancer Symposium (SABCS), demonstrated that the investigational combination generated promising anti-tumor activity and a manageable safety profile.

The exploratory analyses comprised 24 patients, including 10 with ccHER2-positive disease. Seventeen of 24 samples were evaluable for CD47 expression, including samples from nine of the 10 ccHER2-positive patients. Patients received zanidatamab plus evorpacept at dosages of 20 mg/kg (n=3) or 30 mg/kg (n=21). As of the August 1, 2024 data cut-off, key findings from the analyses include:

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 expression (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. In comparison, among the patients with ccHER2-positive disease and low CD47 expression (defined as total membrane staining of <20%), cORR was 25% (n=1/4) and mPFS was 3.4 months.

"The findings from these exploratory analyses provide additional evidence that adding evorpacept to HER2-targeted therapies may generate durable responses in heavily pretreated HER2-positive breast cancers, including in patients in the post-ENHERTU setting," said Barbara Klencke, M.D., Chief Medical Officer at ALX Oncology. "They also further support the use of a biomarker-driven approach to predict treatment response, as we previously observed in the HER2-positive gastric cancer setting. We designed the ongoing ASPEN-09-Breast Phase 2 trial of evorpacept plus trastuzumab and chemotherapy to provide additional insight into this approach and, we hope, move closer to delivering a new therapeutic option for this group of patients."

Het abstract van de fase Ib/II studie waarvan het volledig studieverslag ook gratis is te te lezen of te downloaden:

Abstract

Background:
Patients (pts) with HER2-expressing breast cancer (BC) are in need of novel therapies, including chemotherapy-free treatments and more options post-progression on available therapies, such as trastuzumab deruxtecan (T-DXd). Zanidatamab (zani) is a HER2-targeted bispecific antibody that binds two domains on HER2, leading to crosslinking of adjacent HER2 molecules and multiple mechanisms of action, including inhibition of growth signaling, complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and antibody-dependent cellular phagocytosis (ADCP). Evorpacept (evo) is a high-affinity CD47-blocker with an inactive IgG Fc region designed to enhance ADCP. Here, we report results from a phase 1b/2 trial of zani + evo in advanced HER2-expressing cancers.

Methods:

This two-part, open-label, multicenter study (NCT05027139) included pts with previously treated, inoperable, locally advanced, or metastatic (m) HER2-expressing (by local or central assessment) cancers. Part 1 evaluated safety/tolerability and established the recommended dose (RD) for Part 2. The primary objective in Part 2 was to evaluate the antitumor activity by cORR per RECIST 1.1 in HER2-positive (HER2+) mBC (cohort 1), HER2-low mBC (IHC1+ or IHC2+/ISH negative; cohort 2), and other HER2-overexpressing advanced tumors (cohort 3). DCR, DOR, PFS, OS, and safety were secondary endpoints. Prophylactic treatment for infusion-related reactions (IRRs) was mandatory. Based on the IRR rate in the first 25 pts enrolled, the protocol was amended to reverse the dosing order to zani followed by evo.

Results:

As of March 27, 2024, enrollment was complete with a total of 52 pts; 44 at the RD (cohort 1, n=21; cohort 2, n=15; cohort 3, n=8). Median age (range) was 59 (34-81) yrs; 15 pts (29%) had a history of brain metastasis, and 15 pts (29%) had de novo metastatic disease. By central HER2 assessment, 9/21 (43%) pts in cohort 1 had HER2+ mBC and 14/15 (93%) pts in cohort 2 had HER2-low mBC. The median number of prior systemic regimens in the metastatic setting was 6 in cohort 1, 5 in cohort 2, and 3.5 in cohort 3. All pts in cohort 1 and 5 pts in cohort 2 had prior T-DXd. Median follow-up was 7 months, with 8 pts on treatment at data cutoff. In Part 1, there were two dose-limiting toxicities, both grade 3 IRRs that resolved following treatment discontinuation. The Part 2 RD was zani 1200 mg (pts <70 kg) or 1600 mg (pts ≥70 kg) + evo 30 mg/kg IV Q2W. Among all 52 pts, treatment-related (zani or evo) adverse events (TRAEs) of any grade occurring in ≥20% of pts were diarrhea (62%), fatigue (31%), nausea (27%), and IRRs (21%). Grade 3 TRAEs occurring in ≥2 pts were diarrhea (6%) and IRRs (4%). There were no grade 4 or 5 TRAEs. Three (6%) pts had serious TRAEs (dyspnea, GGT increase, and IRR; 1 pt each). TRAEs of special interest included 1 (2%) pt with a grade 2 LVEF decrease and 12 (23%) pts with IRRs, 11 of whom had the event before the dosing order was reversed. No non-infectious pulmonary toxicities occurred. TRAEs led to treatment discontinuation and dose reductions in 2 pts (4%) each. Among response-evaluable pts treated at the RD, in cohort 1 (n=19) the cORR (95% CI) was 37% (16, 62) and the DCR (95% CI) was 74% (49, 91). The median DOR (range) was not reached (2-22 months). In the 9/19 pts in cohort 1 with centrally confirmed HER2+ mBC, the cORR (95% CI) was 56% (21, 86) and the DCR (95% CI) was 78% (40, 97). For cohort 2 (n=15), the cORR (95% CI) was 20% (4, 48) and the DCR (95% CI) was 40% (16, 68). The median DOR (range) was 6 (4-7) months. Additional efficacy results (including PFS) will be presented at the congress.

Conclusions:

Zani + evo showed a manageable safety profile and promising antitumor activity, particularly in pts with heavily pretreated HER2+ mBC, including prior exposure to T-DXd. Further development of this novel chemotherapy-free regimen is warranted.

Citation Format: Alberto Montero, Kari B. Wisinski, Bruno Fang, Kelly E. McCann, Sara Hurvitz, Kay T. Yeung, Ritesh Parajuli, Jorge Chaves, Adam Brufsky, Peter A. Kaufman, Manish R. Patel, Timothy Pluard, Bob Salim, Kavita V. Shah, Shanhong Guan, Athanasios C. Tsiatis, Sophia Randolph, Funda Meric-Bernstam. Zanidatamab in combination with evorpacept in HER2-positive and HER2-low metastatic breast cancer: Results from a phase 1b/2 study . In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr PS8-09.

borstkanker Her2 positief, Evorpacept, Zanidatamab, immuuntherapie, hormoongevoelig, CD47 expressie