Participants
NSCLC, ovarian cancer, colorectal cancer, squamous cell cancer of the anus, human papillomavirus, CRC, head and neck squamous cell carcinoma, tumours, ATM, tumour, HNSCC, HGSOC, mCRPC
NON-SMALL CELL LUNG CANCER, OVARIAN CANCER, COLORECTAL CANCER, SOLID TUMOUR, TUMOURS, DNA DAMAGE, TUMOUR, NSCLC, METASTATIC CASTRATION-RESISTANT PROSTATE CANCER
Participants in the dose-escalation phase included patients with solid tumours who had relapsed or were progressing after having had standard-of-care chemotherapy. They were required to have World Health Organization (WHO) performance status 0–1 and organ function within limits of standard Phase 1 studies (Supplementary Methods).Tumour type-specific expansion cohorts recruited prospectively identified genetically-defined patients who met the above eligibility criteria and had one of the following 6 tumour types: colorectal cancer (CRC); high-grade serous ovarian cancer (HGSOC) further designated as those with or without CCNE1 gene amplification and those with CCNE1 gene amplification (or alternative genetic alteration with similar functional effect); metastatic castration-resistant prostate cancer (mCRPC); non-small cell lung cancer (NSCLC); or head and neck squamous cell carcinoma (HNSCC) or squamous cell cancer of the anus (SCCA). Patients in these cohorts had their tumours (archival or fresh tissue) prospectively sequenced and were required to have aberrations in one or more of the following categories: (a) tumour suppressor genes regulating G1 such as RB1, TP53, and for patients with HNSCC or SCCA, positive human papillomavirus (HPV) status was also acceptable for eligibility; (b) DNA damage response pathway ATM, BRCA1, BRCA2; (c) genetic indicators of replicative stress such as gain of function/amplification of CHK1 or ATR; d) oncogenic driver such as KRAS or MYC (Supplementary Table 