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Background HER2/neu is overexpressed in 15-25% of gastric cancer patients and associated with poor prognosis. Treatment with recombinant monoclonal Abs against HER2/neu is effective yet alternatives are needed due to cost and global availability issues. Thus a peptide vaccine (IMU-131) was developed, consisting of 3 fused B-cell epitopes (p467) from the HER2/neu extracellular domain coupled to CRM197 and administered with the adjuvant Montanide. The present study evaluated the optimal/safe vaccine dose leading to immunogenicity and clinical responses. Methods In an open-label multicenter Phase Ib trial (SE-Asia & Eastern Europe), 14 patients with HER2/neu overexpressing ( ++/ +++) gastric adenocarcinoma were recruited to receive 3 injections of IMU-131 (days 0, 14, 35) in combination with chemotherapy (CT). Dose escalation (10, 30 and 50 µg) was performed in 3 cohorts (C) to evaluate safety, immunogenicity and clinical responses. Results No SAEs related to IMU-131 administration were reported. Eleven patients were evaluable for vaccine-specific immune responses and RECIST assessment. Higher HER2-specific IgG levels were observed in C2 (30 µg) vs. C1 (10 µg). 3/5 patients in C2 showed moderate or little increase in HER2-specific Abs, while all C3 patients (50µg) responded with moderate to high Ab levels. According to RECIST, 1 patient showed complete response, 5 partial response and 4 stable disease. Strong correlation between high Ab levels and clinical responses was observed in C3, while this was only moderate in C2. Capacity to inhibit HER2 phosphorylation was tested in patient sera and could be detected in association with strong tumor reduction. Furthermore, patients with good clinical responses, but low Ab titers featured cellular responses with high IFNγ and TNFα/IL-10 ratios. Conclusions The vaccine was well tolerated and safe with Ab responses at the highest dose showing strong correlation with clinical responses. Currently, the 50 µg dose is being evaluated in a Phase II trial with two arms (IMU 131 + CT and CT only). Clinical trial identification NCT02795988. Legal entity responsible for the study Imugene Ltd. Funding Imugene Ltd. Disclosure U. Wiedermann: Research grant / Funding (institution), Officer / Board of Directors, CSO until September 2018: Imugene; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Themis. I. Bulat: Advisory / Consultancy, Research grant / Funding (self), Full / Part-time employment: Arensia Exploratory Medicine . T. Yau: Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb. M. Maglakelidzde: Advisory / Consultancy, Research grant / Funding (self), Full / Part-time employment: ARENSIA Exploratory Medicine . T. Ungtrakul: Travel / Accommodation / Expenses: AstraZeneca. C.C. Zielinski: Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): MSD; Honoraria (self), Advisory / Consultancy, Officer / Board of Directors, Scientific Advisory Board Member until June 2018: Imugene; Honoraria (self), Advisory / Consultancy: Ariad; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy: Merrimack; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: KGaA; Honoraria (self), Advisory / Consultancy: Fibrogen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy: Tesaro; Honoraria (self), Advisory / Consultancy: Gilead; Honoraria (self), Advisory / Consultancy: Servier; Honoraria (self), Advisory / Consultancy: Shire; Honoraria (self), Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: Athenex. L. Chong: Honoraria (self), Advisory / Consultancy, Leadership role, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: Imugene Ltd. N. Ede: Leadership role, Research grant / Funding (institution), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Licensing / Royalties, Full / Part-time employment: Imugene Ltd. A. Good: Advisory / Consultancy, Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Imugene Ltd; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Kazia Therapeutics; Shareholder / Stockholder / Stock options: Living Cell Technologies. All other authors have declared no conflicts of interest.

Background Cosibelimab is a high affinity, fully-human IgG1 monoclonal antibody (mAb), with functional Fc domain capable of inducing ADCC, that directly binds to programmed death ligand-1 (PD-L1) and blocks the PD-L1 interaction with the programmed death receptor-1 (PD-1) and B7.1 receptors. Cosibelimab is being evaluated in a multicenter phase 1 study (NCT03212404) in pts with advanced cancers. We present preliminary safety, efficacy and PK data. Methods Pts were ≥18 years old with advanced cancers and adequate organ function. In dose escalation, pts received cosibelimab administered intravenously at sequential fixed doses of 200 mg, 400 mg, or 800 mg every 2 weeks (q2w) or 1200 mg every 3 weeks (q3w) using a 3 + 3 design. Following dose escalation, multiple tumor-specific expansion cohorts are being enrolled at 800 mg q2w to further evaluate safety and efficacy. Results As of April 23, 2019, 65 pts (47M/18F, median age 64 years) with diverse tumor types received cosibelimab in dose escalation and expansion cohorts. Cosibelimab has demonstrated acceptable tolerability with no dose‐limiting toxicities. Treatment‐related adverse events (AEs) occurred in 32/65 (49%) pts, most commonly rash (n = 9, 14%) and fatigue (n = 6, 9%). Treatment‐related grade ≥3 AEs occurred in 5/65 (8%) pts, all grade 3, and included anemia, asthenia, hypertension, hyponatremia, and high blood pressure (n = 1 [2%] each). Cosibelimab demonstrated linear PK with features consistent with marketed anti-PD-L1 mAbs. Thirty-six pts were response evaluable of which 10/36 (28%) pts achieved a partial response by RECIST 1.1 criteria (including cutaneous squamous cell carcinoma, non-small cell lung cancer, head and neck squamous cell carcinoma and melanoma), 17/36 (47%) pts achieved stable disease, and 24/36 (67%) pts experienced target lesion reductions versus baseline. Forty-two pts remain on treatment (range, 1-17+ mos). Conclusions Cosibelimab has demonstrated a safe and well-tolerated safety profile with evidence of durable anti‐tumor activity in several advanced cancers, and linear PK. Cosibelimab is being further evaluated in multiple tumor-specific expansion cohorts. Updated results will be presented. Clinical trial identification NCT03212404. Legal entity responsible for the study Checkpoint Therapeutics, Inc. Funding Checkpoint Therapeutics, Inc. Disclosure P.R. Clingan: Research grant / Funding (institution): Merck Sharp & Dohme Corp; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Bristol Myers; Research grant / Funding (institution): Checkpoint Therapeutics, Inc. A.M. Mant: Research grant / Funding (institution): Checkpoint Therapeutics, Inc. G.E. Richardson: Research grant / Funding (institution): Novotech; Research grant / Funding (institution): Roche; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Alphapharm; Research grant / Funding (institution): Checkpoint Therapeutics. D.M. Kowalski: Research grant / Funding (institution): Checkpoint Therapeutics, Inc. P. Koralewski: Research grant / Funding (institution): Checkpoint Therapeutics, Inc. I. Lugowska: Research grant / Funding (institution): Checkpoint Therapeutics, Inc.; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol Myers; Honoraria (self): Merck; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self): Amgen; Honoraria (self): Janssen; Honoraria (self), Research grant / Funding (institution): Novartis. A. Dechaphunkul: Speaker Bureau / Expert testimony: Roche; Travel / Accommodation / Expenses: Eisai; Research grant / Funding (institution): Checkpoint Therapeutics. C. Charoentum: Research grant / Funding (institution): Roche; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Checkpoint Therapeutics. A. Sookprasert: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Honoraria (self): Eisai; Research grant / Funding (institution): Checkpoint Therapeutics, Inc. V. Sriuranpong: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self): Sanofi; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Eisai; Honoraria (self), Research grant / Funding (institution): Boehringer; Honoraria (self), Research grant / Funding (institution): Taiho; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck Sharp & Dohme; Honoraria (self): Bristol Myers; Advisory / Consultancy: Amgen; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Checkpoint Therapeutics. A. Akopov: Research grant / Funding (institution): Checkpoint Therapeutics, Inc. V. Kozlov: Research grant / Funding (institution): Checkpoint Therapeutics, Inc. N. Fadeeva: Research grant / Funding (institution): Checkpoint Therapeutics, Inc. B. Kasparov: Research grant / Funding (institution): Checkpoint Therapeutics, Inc. N.V. Kovalenko: Research grant / Funding (institution): Checkpoint Therapeutics, Inc. V. Oschepkov: Research grant / Funding (institution): Checkpoint Therapeutics, Inc. L. Gorelik: Shareholder / Stockholder / Stock options, Full / Part-time employment: Checkpoint Therapeutics, Inc. Y. Kunes: Shareholder / Stockholder / Stock options: Checkpoint Therapeutics, Inc. J. Oliviero: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Checkpoint Therapeutics, Inc. D.L. Harris: Research grant / Funding (institution): Merck; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Checkpoint Therapeutics; Research grant / Funding (institution): Targovax.