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The annual ESMO congress is the premier scientific platform to present your oncology research and as such, the ultimate learning experience for congress attendees. Across disciplines and across cultures, ESMO bridges the gap between researchers, clinicians and patients and unites all stakeholders focused on finding the most effective cancer treatment solutions available today.
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Abstract:
Background: Globo H is a glycolipid that is highly expressed in breast cancer (BC). Active immunotherapy with OPT-822, a Globo H¡VKLH conjugate, and the adjuvant OPT-821 in 2 phase (Ph) I trials, induced Globo H specific antibodies which could mediate in vitro binding and cytotoxicity to Globo H expressing BC cells.
Methods: In this international, randomized, double-blind, placebo-controlled Ph II/III trial (NCT01516307), patients (pts) with metastatic BC who had ≤ 2 events of progressive disease (PD) and who achieved at least stable disease (SD) after ≥ 1 anticancer regimen were randomized 2:1 to receive subcutaneous OPT-822 (30 £gg Globo H)/OPT-821 (100 £gg) or control (PBS) on weeks 1, 2, 3, 5, 9, 13, 17, 25, and 37 or until PD, in combination with low-dose cyclophosphamide (300 mg/m2). Hormone therapy was allowed. The primary and secondary efficacy end points were progression-free survival (PFS) and overall survival (OS), correlated with humoral antibody response.
Results: 349 pts were randomized, 348 received study drug (ITT), 168 (48%) received all 9 injections. 70% had hormone receptor positive BC, 13% were triple negative, and 62% received hormone therapy. No difference was observed in PFS (HR, 0.96 [95% CI, 0.74-1.25] P = .77) or in interim OS (HR, 0.79 [95% CI, 0.51-1.22] P = .29). However, PFS and OS were significantly improved in the 50% of pts who developed a Globo H specific IgG response to OPT-822/OPT-821 with a titer ≥ 1:160 at any time during treatment vs control (HR, 0.71 [95% CI, 0.52-0.97] P = .029 for PFS; HR, 0.57 [95% CI, 0.33-0.97] P = .04 for OS) and vs nonresponders (HR, 0.52 [95% CI, 0.37-0.71] P< .0001 for PFS; HR, 0.52 [95% CI, 0.29-0.92] P = .025 for OS), adjusted for baseline disease status/hormone use. In a time-dependent Cox model, PFS was improved in pts who received all 9 injections of OPT vs control (HR, 0.66 [95% CI, 0.42-1.01] P= .057). OPT-822/OPT-821 was well tolerated; the most common drug-related adverse event was grade 1/2 injection reaction.
Conclusion: Vaccination with OPT-822/OPT-821 did not improve PFS in the ITT; however, PFS and interim OS were significantly improved in pts who developed an immune response to the vaccine. These subgroup data will be used to design a definitive Ph III trial. Clinical trial information: NCT01516307
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Heritage: A phase III safety and efficacy trial of the proposed trastuzumab biosimilar Myl-1401O versus Herceptin.
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