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Novel therapy shows promise for advanced gastric cancer
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CHICAGO — The addition of IMAB362 to standard first-line chemotherapy improved survival without increasing toxicity, according to the results of the phase 2 FAST trial presented at the ASCO Annual Meeting.
IMAB362 (Ganymed) is a first-in-class antibody that targets claudin18.2, a tight junction protein expressed by several cancers including gastric and gastroesophageal junction adenocarcinoma.
“These data showed that IMAB362 benefited both cohorts and was well tolerated, but results should be approached with caution,” Salah-Eddin Al-Batran, MD, professor at Goethe University and director of Institute of Clinical Cancer Research at Krankenhaus Nordwest-University Cancer Center in Frankfurt, Germany, said in a press briefing. “FAST provides strong rationale for a phase 3 trial.”
Chemotherapy is the standard first-line treatment for advanced or recurrent gastric cancer. Patients who present with HER-2–positive tumors may also benefit from trastuzumab (Herceptin, Genentech); however, only 15% of gastric cancers are HER-2 positive.
Al-Batran and colleagues sought to evaluate the efficacy and safety of adding IMAB362 to standard chemotherapy for patients with advanced or recurrent gastric and gastroesophageal junction adenocarcinoma.
Enrollment eligibility included claudin18.2 expressions ( 2+ in 40% or more tumor cells), ECOG performance score of 0 to 1, and HER-2–negative disease.
The analysis included data from 161 patients (median age, 58 years; 64% men). Of these patients, 80% had gastric cancer, 16% had gastroesophageal junction adenocarcinoma and 4% had esophageal cancer.
All patients received the standard-of-care chemotherapy regimen EOX, or epirubicin (50mg/m2 on day 1), oxaliplatin (130 mg/m2 on day 1) and capecitabine (625 mg/m2 twice daily days 1-21 once on day 22). Researchers randomly assigned patients to receive EOX alone (n = 84) or with IMAB362 (n = 77; 800 mg/m2 loading dose, 600 mg/m2 daily thereafter). The researchers extended the study to include 85 patients in a high-dose IMAB362 arm (1,000 mg/m2), but these data are not yet mature.
PFS served as the study’s primary endpoint.
Results showed the addition of IMAB362 to EOX chemotherapy improved median PFS (7.9 months vs. 4.8 months; HR = 0.47; P = .0001) and median OS (13.2 months vs. 8.4 months; HR = 0.51; P = .0001).
Researchers then conducted a subgroup analysis of patients with high claudin18.2 expression, or 2+/3+ intensity in 70% or more tumor cells. Results showed this group of patients demonstrated even greater benefit with IMAB362 in terms of PFS (7.2 months vs. 6.1 months; HR = 0.36; P < .0005) and OS (16.7 months vs. 9 months; HR = 0.45; P < .0005).
The objective response rate was 39% with EOX plus IMAB362 and 35% for EOX alone.
Treatment-related adverse events did not increase significantly with IMAB632. The rate of grade 3 to grade 4 adverse events was 11.7% in the combination arm and 7.1% in the EOX arm.
Common grade 1 and 2 IMAB362 treatment-related adverse events were vomiting, neutropenia and anemia.
“As claudin18.2 is abundant in gastric tumors, we estimate that half of all patients with advanced gastric cancer may be candidates for this new treatment,” Al-Batran said in a press release. “In addition, this unique target is not present in any healthy tissues except the lining of the stomach, thereby minimizing treatment side effects.” – by Nick Andrews
Reference:
Al-Batran SE, et al. Abstract LBA4001. Presented at: ASCO Annual Meeting; June 3-7, 2016; Chicago.
Disclos ure: Al-Batran reports consultant/advisory roles with, speakers’ fees and research funding from Celgene, Hospira, Lilly, Medac, Merck, Nordic Bioscience, Novartis, Roche, Vifor Pharma. Please see the abstract for a full list of the researchers’ relevant financial disclosures.