A phase 3 trial of adagloxad simolenin/OBI-821 in patients with high-risk early-stage triple-negative breast cancer.

2551 Background: Adagloxad simolenin (AS) is a therapeutic cancer vaccine composed of Globo H linked to the carrier protein keyhole limpet hemocyanin. OBI-821 is an adjuvant administered with AS to strengthen immune response. This phase 3 trial assessed safety/efficacy of AS/OBI-821 in patients with triple negative breast cancer (TNBC; NCT03562637). Methods: Eligible patients for this randomized, open-label trial were adults with high-risk (≥1cm residual primary, ≥1 residual axillary node after neoadjuvant chemotherapy, or stage IIB or III cancer treated with adjuvant chemotherapy alone), primary localized early-stage, Globo H-positive (H-score ≥15) TNBC. Patients were required to have received ≥4 cycles of standard taxane- and anthracycline-based chemotherapy. Patients were randomized 1:1 to receive standard of care (SOC; observation alone [29%], capecitabine [69%], or a checkpoint inhibitor ± capecitabine [2%]) or AS/OBI-821 and SOC (observation alone [26.6%], capecitabine [69.6%], or a checkpoint inhibitor ± capecitabine [3.8%]). Patients in the AS/OBI-821 arm received 4 weekly doses of study drug administered via subcutaneous injection, followed by 4 biweekly doses, 4 doses every 4 weeks, then doses every 8 weeks up to 100 weeks. The primary endpoint was invasive disease-free survival (IDFS); secondary endpoints included safety assessed via treatment-emergent adverse events (TEAEs) and overall survival (OS). Patients were followed for up to 5 years after randomization for OS. Results: The intent-to-treat (ITT) population was comprised of 575 patients, with 286 in the AS/OBI-821 arm, and 289 in the SOC arm. Patients were a median age of 51 years (range 24-85), all were female, and most were white (52.7%). A total of 5.2% of patients had stage I cancer, 50.3% had stage II, and 37.1% had stage III. IDFS in the AS/OBI-821 arm was not statistically different than in the SOC arm (IDFS hazard ratio [HR], 1.23 [95% CI: 0.88, 1.73]; P = 0.23). Three-year IDFS rate was 54.5% for AS/OBI-821 arm and 56.4% for the SOC arm. Similar pattern was observed for OS with HR = 1.36 [95% CI: 0.77, 2.38). TEAEs occurred in 79.6% of patients in the AS/OBI-821 arm and 66.7% in the SOC arm. The most common TEAEs in the AS/OBI-821arm were palmar-plantar erythrodysaesthesia syndrome (18.7%), fatigue (11.6%), and headache (11.3%). Serious TEAEs occurred in 5.3% of patients in the AS/OBI-821 arm vs 6.2% in the SOC arm. One patient (0.4%) in the AS/OBI-821 arm had a TEAE of interstitial lung disease, assessed as unlikely related to treatment and one patient (0.3%) in the SOC arm had acute coronary syndrome that led to death. Conclusions: In this phase 3, randomized, open-label trial, AS/OBI-821 was well-tolerated, with a safety profile similar to SOC. IDFS and OS were similar between the AS/OBI-821 and SOC arms. The trial was terminated per recommendation by the Data and Safety Monitoring Board as it met prespecified futility criteria. Clinical trial information: NCT03562637 .