"In the updated analysis from this Phase 2 study, we have observed a median overall survival of 20.5 months with response rates of 48% for patients with HER2 IHC3-positive and PD-L1-positive metastatic gastroesophageal adenocarcinoma treated with margetuximab and pembrolizumab in the second line setting, and with a safety profile that is similar to pembrolizumab monotherapy. Notably, a response rate of 47% with a median overall survival of 13.1 months has previously been reported for gastroesophogeal patients treated with first line standard of care, trastuzumab and chemotherapy,” said
In the Phase 2 (NCT02689284) open-label, dose escalation and expansion study, 92 patients with HER2-positive (IHC3-positive or IHC2-positive/FISH-positive) GEA, including 61 patients with gastric cancer (GC) and 31 patients with gastroesophageal junction cancer (GEJ), were treated at the recommended phase 2 dose (RP2D) of 15 mg/kg margetuximab and 200 mg pembrolizumab, both administered every three weeks, and were included in the analysis. Patients in the study were enrolled irrespective of PD-L1 expression status. Loss of HER2 expression after treatment with trastuzumab has previously been reported in GEA patients, and was observed in some patients in the current study. Pembrolizumab is provided by
Data are reported as of
Response rates, median progression-free survival (PFS) and overall survival (OS) observed in the ongoing study are summarized in the following table:
|Gastroesophageal Adenocarcinoma (GEA = GC + GEJ)||Gastric Cancer |
|ORR||DCR||Median PFS (months)||Median OS (months)||ORR||DCR||Median PFS (months)||Median OS (months)|
|All Patients||20*/92 |
|50/92 (54.4%)||2.7||12.5||18*/61 (29.5%)||40/61 (65.6%)||4.1||13.9|
|HER2 IHC3+||20*/71 (28.2%)||45/71 (63.4%)||4.3||13.9||18*/55 (32.7%)||38/55 (69.1%)||4.7||14.6|
|HER2 IHC3+/PD-L1+||12/25 (48.0%)||19/25 (76.0%)||4.8||20.5||12/23 (52.2%)||19/23 (82.6%)||5.5||20.5|
*Three unconfirmed; ORR=objective response rate (CR+PR); DCR=disease control rate (CR+PR+SD)
Consistent with prior studies of margetuximab in other tumor types, correlative analyses of samples from GEA patients treated in the study showed an increase in anti-HER2 specific T-cell immunity.
"These data provide strong rationale for combining the innate and adaptive immune enhancing properties of margetuximab with checkpoint blockade in patients with HER2-positive gastroesophageal adenocarcinoma," said
Margetuximab Presentations at
- Abstract #2812: Catenacci, et al. "Margetuximab (M) + pembrolizumab (P) for treatment of patients (pts) with HER2+ gastroesophageal adenocarcinoma (GEA) post-trastuzumab (T): Survival analysis" – Poster Discussion 1188
- Abstract #2794: Park, et al. "Determinants of response of HER2+ gastric cancer (GC) vs gastroesophageal junction adenocarcinoma (GEJ) to margetuximab (M) plus pembrolizumab (P) post trastuzumab (T)" – Poster Discussion 1189
- Abstract #2547: Rutella, et al. "Evaluation of tumor microenvironment identifies immune correlates of response to combination immunotherapy with margetuximab (M) and pembrolizumab (P) in HER2+ gastroesophageal adenocarcinoma (GEA)" – Poster 123
These posters will be available for download from the Events & Presentations page on
Margetuximab is an investigational monoclonal antibody that targets the HER2 oncoprotein. HER2 is expressed by tumor cells in breast, gastroesophageal and other solid tumors. Margetuximab was designed to provide HER2 blockade and has similar HER2 binding and antiproliferative effects as trastuzumab. In addition, margetuximab has been engineered with MacroGenics’ Fc Optimization technology to enhance the engagement of the immune system and affect killing of cancer cells through antibody dependent cellular cytotoxicity (ADCC). Beyond GEA, margetuximab is also being evaluated in combination with chemotherapy in the Phase 3 SOPHIA study for the treatment of patients with metastatic HER2-positive breast cancer who have previously been treated with anti-HER2-targeted therapies.
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Any statements in this press release about future expectations, plans and prospects for the Company, including statements about the Company's strategy, future operations, clinical development of the Company's therapeutic candidates, milestone or opt-in payments from the Company's collaborators, the Company's anticipated milestones and future expectations and plans and prospects for the Company and other statements containing the words "subject to", "believe", "anticipate", "plan", "expect", "intend", "estimate", "project", "may", "will", "should", "would", "could", "can", the negatives thereof, variations thereon and similar expressions, or by discussions of strategy constitute forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the uncertainties inherent in the initiation and enrollment of future clinical trials, expectations of expanding ongoing clinical trials, availability and timing of data from ongoing clinical trials, expectations for regulatory approvals, other matters that could affect the availability or commercial potential of the Company's product candidates and other risks described in the Company's filings with the
Anna Krassowska, Ph.D., Vice President, Investor Relations & Corporate Communications Jim Karrels, Senior Vice President, CFO 1-301-251-5172, email@example.com
Source: MacroGenics, Inc.