“The overall findings of the study are positive, and support the promise of nimotuzumab in this important global cancer market. Although not powered for statistical significance, in subgroup analyses these data demonstrated that EGFR-positive patients treated with nimotuzumab showed a potential improvement of Progression Free Survival and Overall Survival in gastric cancer. This is consistent with evidence that nimotuzumab selectively targets tissues over-expressing EGFR,” said Dr. Nick Glover, President and CEO of YM BioSciences. “The authors of the study conclude that the selection of gastric cancer patients by EGFR status might be effective for future studies of nimotuzumab, and indicate that a Phase III clinical trial should be performed to examine these findings.”
The results were reported in a poster being presented on January 20, 2011 at the ASCO Gastrointestinal Cancers Symposium in San Francisco, entitled: “Randomized phase II study of nimotuzumab, an anti-EGFR antibody, plus irinotecan in patients with 5-fluorouracil-based regimen-refractory advanced or recurrent gastric cancer in Korea and Japan: Preliminary results”.
Trial Design and Results:
The study is a Phase II multi-center, randomized, open-label trial evaluating nimotuzumab (“N”) (400 mg, IV weekly) plus irinotecan (“I”) (150 mg/m2 IV every two weeks) compared to irinotecan alone in patients with advanced or recurrent gastric cancer who are refractory to a 5-fluorouracil-based regimen. The efficacy analysis was conducted six months after completion of randomization with a median follow-up period of 197 days.
The primary endpoint was PFS (Progression Free Survival) and the secondary endpoints included safety, ORR (Overall Response Rate), OS (Overall Survival), and PK. Eighty-two eligible patients (ECOG PS 0-1, one prior regimen) were treated with N+I (n = 40) or I (n = 42). Tumor tissues collected from 48 patients (N+I arm: 26, I arm: 22) were analyzed for EGFR and K-ras. EGFR status (0/1+/2+/3+) examined by immunohistochemistry was 44%/25%/13%/17% respectively.
• Median PFS was 73.0 days in the N+I arm compared with 85.0 days in the I arm (HR 0.860; 95% CI, 0.516, 1.435).
• Overall Survival was 293.0 days in the N+I arm compared with 227.0 days in the I arm among 82 patients (HR 0.717; 95% CI, 0.420, 1.224).
• In the subgroup analyses, the hazard ratio in PFS for patients with EGFR 1+/2+/3+ was 0.463 (95%CI, 0.177, 1.212) and that of EGFR 2+/3+ was 0.341 (95% CI, 0.080, 1.457) and the hazard ratio in OS was 0.584 (95% CI, 0.242, 1.409) and 0.295 (95% CI, 0.077, 1.129), respectively.
• The incidence of adverse events was similar between both arms.
• No adverse events of grade 3 skin rash or grade 3 infusion-related reactions were reported.
Nimotuzumab is a humanized monoclonal antibody in development worldwide, targeting multiple tumor types primarily in combination with radiation and chemoradiation. It is importantly differentiated from other currently marketed EGFR-targeting agents due to its enhanced side-effect profile. Nimotuzumab's anti-tumor activity has led to its approval for marketing in 25 countries. In more than 10,000 patients reported as having been treated with nimotuzumab worldwide to date, Grade IV incidents of radiation dermatitis and incidents of severe rash have been only rarely observed, and reports of the other severe side-effects that are typical of EGFR-targeting molecules have been equally rare. Nimotuzumab is licensed to YM's majority-owned, Canadian subsidiary, CIMYM BioSciences Inc., by CIMAB S.A., and was developed at the Center of Molecular Immunology.