PCA062 / Novartis - LARVOL DELTA

A First-in-Human, Phase 1, Multicenter, Open-label, Dose-Escalation Study of PCA062, an Antibody-Drug Conjugate Targeting P-Cadherin, in Patients with Solid Tumors. (PubMed, Mol Cancer Ther) - P1 | "One patient out of 47 achieved a partial response and there was no correlation between tumor P-cadherin expression and clinical efficacy. Due to limited anti-tumor activity at the maximally tolerated dose level, Novartis has terminated clinical development of PCA062 (NCT02375958)."

Journal • P1 data • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Head and Neck Cancer • Hematological Disorders • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thrombocytopenia • CDH3

PCA062, a P-cadherin targeting antibody-drug-conjugate, displays potent anti-tumor activity against P-cadherin-expressing malignancies. (PubMed, Mol Cancer Ther) - "Genome-wide CRISPR screens reveal that expression of the multi-drug resistant gene ABCC1 and the lysosomal transporter SLC46A3 differentially impact tumor cell sensitivity to PCA062. The preclinical data presented here suggest that PCA062 may have clinical value for treating patients with multiple cancer types including basal-like breast cancer."

Journal • Breast Cancer • Oncology • Solid Tumor • ABCC1 • CDH3

Tofacitinib, an Oral Janus Kinase Inhibitor, in the Treatment of Ulcerative Colitis: An Interim Analysis of an Open-Label, Long-Term Extension Study With up to 4.9 Years of Treatment (ACG 2018) - P3; "Safety and efficacy of tofacitinib for UC are being evaluated in an ongoing, open-label, long-term extension (OLE) study [2]. We present an update (as of Nov 10 2017) of previous safety and efficacy data [2] of the OLE study (NCT01470612) in completers or treatment failures in OCTAVE Sustain (NCT01458574) and non-responders in OCTAVE Induction 1/2. Of 944 pts who received ≥1 dose of study drug (for up to 4.9 years), 326 (34.5%) discontinued due to insufficient clinical response, and 65 (6.9%) due to adverse events (AEs) excl. worsening UC. Serious and severe AEs occurred in 14.8% and 9.9% of pts, respectively."

Clinical • P3 data

Using genome-wide CRISPR screen to understand resistance mechanisms to PCA062, a P-cadherin targeting antibody-drug conjugate (AACR 2019) - "Lysosomal transporter SLC46A3 and Saga transcription complex components are strong rescue hits for PCA062 in HCC1954. These data suggest that in addition to target expression level and cell intrinsic sensitivity to payload, genes involved in ADC internalization and payload cytoplasmic accumulation will also impact tumor cell sensitivity to ADCs."

Risk factors for splenic hilum lymph node metastasis in patients with gastric cancer: A systematic review and meta-analysis (IGCC 2019) - "...Methods Comprehensive search for English databases of PubMed, Web of Science, EMBASE, Cochrane Central Register of Controlled Trials, from each database’s inception to Nov 10, 2017 at first...Conclusions Our systematic review and meta-analysis is the largest and most comprehensive study of risk factors related to splenic hilum lymph node metastasis of gastric cancer so far. These results verify the significance of many previously reported factors, while providing a novel, robust quantitative risk for each risk factor and the associated splenic hilum lymph node metastasis."

Retrospective data • Review