On October 23, 2026 MacroGenics, Inc. (NASDAQ: MGNX), a clinical-stage biopharmaceutical company focused on developing innovative antibody-based therapeutics for the treatment of cancer, reported positive interim data from its Phase 1 study evaluating MGC026, a B7-H3-directed antibody-drug conjugate (ADC), in patients with advanced solid tumors. These Phase 1 data were presented today at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2026 Congress in Madrid, Spain. These results demonstrated durable activity across a broad range of solid tumors, which the Company believes supports expanded development of MGC026 in front-line metastatic squamous cell carcinoma of the head and neck (SCCHN) in combination with pembrolizumab.
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"The emerging profile of MGC026 reinforces our conviction that this molecule has the potential to play an important and differentiated role in the treatment of advanced solid tumors," said Eric Risser, President and Chief Executive Officer of MacroGenics. "We believe MGC026 is well positioned through the combination of a highly selective B7-H3-targeting antibody, a proprietary drug-linker technology and a potent TOP1 inhibitor payload."
Overall MGC026 Safety and Dose Selection
As of the September 1, 2026 data cutoff, 85 patients had been treated across the dose-escalation and dose-expansion cohorts. Across this full safety population, treatment-related adverse events (TRAEs) led to discontinuation in 5% of patients, and no Grade 5 TRAEs were reported. Grade ≥3 TRAEs occurred in 51% of patients. The most common Grade ≥3 TRAEs observed in ≥10% of participants were neutropenia (27%) and anemia (25%). No cases of interstitial lung disease (ILD), pneumonitis or ocular toxicity were observed.
In the 32-patient dose-escalation portion, patients with advanced and metastatic solid tumors received MGC026 at doses ranging from 1 mg/kg to 9 mg/kg administered every three weeks (Q3W) and had received a median of four prior lines of systemic therapy (range 1-8). Pharmacokinetic analyses demonstrated dose-dependent exposure for the ADC and unconjugated payload, supporting selection of the 7.5 mg/kg Q3W regimen for continued evaluation across all tumor-specific expansion cohorts.
Durable Antitumor Activity Across Solid Tumors in Dose Escalation
Among 17 response-evaluable patients representing 10 different tumor types who received MGC026 at doses of at least 6 mg/kg in dose escalation, the confirmed objective response rate was 29% (5/17), and the disease control rate was 65% (11/17). Responses were durable, with a median duration of response (mDOR) of 10.2 months. MacroGenics believes these findings highlight the potential of MGC026 to deliver meaningful and durable clinical benefit in a patient population with advanced solid tumors that were refractory to prior treatments.
Encouraging Activity in Heavily Pretreated SCCHN Patients
As part of the Phase 1 study, MacroGenics is evaluating MGC026 in an ongoing Simon’s 2-stage tumor-specific expansion cohort in recurrent/metastatic SCCHN. The study is designed to enroll 40 patients treated at a dose of 7.5 mg/kg Q3W. The interim results reported here are based on a September 1, 2026 data cutoff and include 27 patients evaluable for safety and 22 patients evaluable for response.
Patients were heavily pretreated, with 46% of the response-evaluable participants having received three prior lines of systemic therapy and 41% having received four or more prior lines (median was 3 prior lines [range 1-7]). MGC026 demonstrated encouraging antitumor activity in these SCCHN patients, achieving a best overall response rate of 27% (6/22), including four confirmed and two unconfirmed partial responses (PRs), and a disease control rate of 64% (14/22). Activity appeared higher among patients with HPV-positive disease, with five of the responses observed (5/16) in this population.
MGC026 demonstrated a manageable safety profile in this heavily pretreated and difficult-to-treat SCCHN population. No TRAEs led to treatment discontinuation, and no cases of ILD, pneumonitis or ocular toxicity were observed. Grade ≥3 TRAEs occurred in 48% of patients. The only two Grade ≥3 TRAEs observed in ≥10% of participants were anemia (30%) and neutropenia (26%). The TRAEs observed in Stage 1 were well managed and reversible. Many of the patients who experienced hematologic toxicities had previously received platinum- and/or taxane-based chemotherapy. Based on these encouraging initial findings, enrollment continues in Stage 2 of the ongoing Phase 1 study, with updated data expected in mid-2027.
"These preliminary Phase 1 data for MGC026 are encouraging and demonstrate a manageable safety profile and promising antitumor activity in heavily pretreated patients with advanced solid tumors," said Apostolia M. Tsimberidou, M.D., Ph.D., M.B.A., of The University of Texas MD Anderson Cancer Center and the lead principal study investigator. "Importantly, of 22 heavily pretreated patients with SCCHN (expansion cohort), six (27.3%) had a partial response. There was no drug-related treatment discontinuation, and no pneumonitis, ocular toxicities, or unexpected toxicities were noted. Together, these findings support the continued clinical development of MGC026 in SCCHN and across multiple tumor types, including evaluation in combination regimens and earlier lines of therapy."
Next Development Steps in SCCHN
MacroGenics believes the emerging profile of MGC026 supports evaluation in earlier-line treatment settings, where the molecule’s orthogonal mechanism of action and non-overlapping toxicity profile may potentially complement immune checkpoint inhibition. The Company plans to initiate an expansion cohort in early 2027 evaluating MGC026 in combination with pembrolizumab in front-line patients with PD-L1 positive (CPS ≥1) recurrent or metastatic SCCHN.
Commenting on the emerging SCCHN treatment landscape, Barbara Burtness, M.D., Anthony N. Brady Professor of Medicine and Chief of Head and Neck Cancers, Yale Cancer Center, commented: "As new therapies emerge in head and neck cancer, differentiation will increasingly depend not only on antitumor activity, but also on durability, tolerability and the ability to be incorporated into combination regimens. I believe the developing clinical profile of MGC026 positions this agent favorably among emerging therapies. The planned pembrolizumab combination study represents an important next step in determining the potential role of MGC026 in earlier treatment settings."
Poster Presentation Details
Title: Phase 1, first-in-human study of MGC026, a B7-H3–targeted antibody-drug conjugate (ADC) in advanced solid tumors
Lead author: Rachel E. Sanborn, M.D.
Session: Developmental therapeutics
Poster number: 1020P
Date and time: Friday, October 23, 2026, from 15:15 to 16:00 CEST
A copy of the above ESMO (Free ESMO Whitepaper) poster presentation and a supplemental slide presentation are available on the Company’s Investor Relations website or through the direct links below:
•ESMO poster presentation
•Supplemental slide presentation
About MGC026
MGC026 is an investigational antibody-drug conjugate (ADC) targeting B7-H3, a protein with expression across the tumor microenvironment, including on tumor cells, tumor-associated stroma, and tumor-associated vasculature. MGC026 incorporates Synaffix’s proprietary ADC technology and the SYNtecan topoisomerase I inhibitor-based linker-payload, which consists of a cleavable, exatecan-based cytotoxic payload conjugated at a drug-to-antibody ratio (DAR) of 4. The ongoing Phase 1 study of MGC026 is an open-label clinical trial evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of MGC026 in patients with advanced solid tumors. The study is currently evaluating patients with SCCHN, endometrial cancer, melanoma, and soft tissue sarcoma. Additional information about the study is available at www.clinicaltrials.gov using the identifier NCT06242470.
(Press release, MacroGenics, OCT 23, 2026, View Source [SID1234673711])