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Antitumor activity of margetuximab (M) plus pembrolizumab (P) in patients (pts) with advanced HER2+ (IHC3+) gastric carcinoma (GC).

Publication ,  Conference
Catenacci, DVT; Lim, KH; Uronis, HE; Kang, Y-K; Ng, MCH; Gold, PJ; Enzinger, PC; Lee, KW; Lacy, J; Park, SH; Yen, J; Odegaard, J; Franovic, A ...
Published in: Journal of Clinical Oncology
February 1, 2019

65 Background: Trastuzumab (T) + chemo is standard first-line therapy (tx) for HER2+ gastroesophageal adenocarcinoma (GEA) pts, though progression ensues in 6-8 months. The approved second-line tx is ramucirumab +/- paclitaxel (R+PAC). Pts with GC are less responsive to R+PAC than gastroesophageal junction (GEJ) pts, in particular HER2+ GC, and no anti-HER2 agents are approved in post-T setting. We report results of combination M+P in HER2+ GC pts and describe a biological rationale for this population. M is an anti-HER2 mAb Fc optimized for enhanced binding to activating FcgRIIIa (CD16A) and decreased binding to inhibitory FcgRIIb (CD32B). M demonstrated an enhanced Fc-dependent MoA, including enhanced ADCC. Methods: HER2+, PD-L1-unselected, second-line GEA pts post T progression received M (15 mg/kg) + P (200 mg) Q3wk. Safety, objective response rate (ORR), median overall & progression-free survival (mOS, mPFS), disease control rate (DCR), circulating tumor DNA, & tumor PD-L1 expression were assessed. Results: To date, 66 GEA pts were dosed; 35 (53%) GC and 31 (47%) GEJ. Overall, 12/66 (18.2%) had tx-related adverse events ≥ grade 3; 5 had drug-related SAEs: dehydration, diabetic ketoacidosis, hypotension and pneumonitis, each a single event, and 2 events of autoimmune hepatitis. Eligibility was based on archival HER2 expression; an exploratory endpoint measured retention of HER2 expression post-T by ERBB2 ctDNA. HER2 expression was lost in 23/56 (41.1%) of pts tested post T. HER2 retention was higher in pts with GC versus GEJ (65.8% vs. 44.8%) and in GEA pts with IHC 3+ vs 2+ archival tumors (61.7% vs 47.4%, respectively). Furthermore, GC had higher PD-L1 expression than GEJ, 53.3 vs. 33.3%, respectively. This coincided with more responses in IHC3+ GC pts, ORR 12/29 (41.4%; 95% CI 23.5-61.1), DCR 21/29 (72.4%; 95% CI 52.8-87.3), mPFS 5.5 months (95% CI 2.3-7.6), mOS not reached, with lower bound of 9.1 months for 95% CI. Enrollment of an additional 25 pts enriched for IHC3+ GC is ongoing. Conclusions: Results suggest that M+P, a chemo-free regimen, demonstrates acceptable tolerability and has encouraging preliminary activity in second-line HER2+ GEA, specifically in GC pts who retain ERBB2 amp prior to second-line tx. Clinical trial information: NCT02689284.

Duke Scholars

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

February 1, 2019

Volume

37

Issue

4_suppl

Start / End Page

65 / 65

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences
 

Citation

APA
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ICMJE
MLA
NLM
Catenacci, D. V. T., Lim, K. H., Uronis, H. E., Kang, Y.-K., Ng, M. C. H., Gold, P. J., … Bang, Y.-J. (2019). Antitumor activity of margetuximab (M) plus pembrolizumab (P) in patients (pts) with advanced HER2+ (IHC3+) gastric carcinoma (GC). In Journal of Clinical Oncology (Vol. 37, pp. 65–65). American Society of Clinical Oncology (ASCO). https://doi.org/10.1200/jco.2019.37.4_suppl.65
Catenacci, Daniel V. T., Kian Huat Lim, Hope Elizabeth Uronis, Yoon-Koo Kang, Matthew C. H. Ng, Philip Jordan Gold, Peter C. Enzinger, et al. “Antitumor activity of margetuximab (M) plus pembrolizumab (P) in patients (pts) with advanced HER2+ (IHC3+) gastric carcinoma (GC).” In Journal of Clinical Oncology, 37:65–65. American Society of Clinical Oncology (ASCO), 2019. https://doi.org/10.1200/jco.2019.37.4_suppl.65.
Catenacci DVT, Lim KH, Uronis HE, Kang Y-K, Ng MCH, Gold PJ, et al. Antitumor activity of margetuximab (M) plus pembrolizumab (P) in patients (pts) with advanced HER2+ (IHC3+) gastric carcinoma (GC). In: Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2019. p. 65–65.
Catenacci, Daniel V. T., et al. “Antitumor activity of margetuximab (M) plus pembrolizumab (P) in patients (pts) with advanced HER2+ (IHC3+) gastric carcinoma (GC).Journal of Clinical Oncology, vol. 37, no. 4_suppl, American Society of Clinical Oncology (ASCO), 2019, pp. 65–65. Crossref, doi:10.1200/jco.2019.37.4_suppl.65.
Catenacci DVT, Lim KH, Uronis HE, Kang Y-K, Ng MCH, Gold PJ, Enzinger PC, Lee KW, Lacy J, Park SH, Yen J, Odegaard J, Franovic A, Baughman JE, Wynter-Horton A, Chen F, Moore PA, Wu T, Davidson-Moncada JK, Bang Y-J. Antitumor activity of margetuximab (M) plus pembrolizumab (P) in patients (pts) with advanced HER2+ (IHC3+) gastric carcinoma (GC). Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2019. p. 65–65.

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

February 1, 2019

Volume

37

Issue

4_suppl

Start / End Page

65 / 65

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences