46 CHAPTER 2 Extended Data Table 2. Opened cohorts Overview of cohorts that have been opened for the first 215 patients who started study treatment. For each cohort cell in the table, the tumour type is indicated in top line, the tumour profile is indicated in the middle line and the number of evaluable or enrolled patients is indicated in bottom line. All patients were required to be refractory or intolerant to standard therapies. ACUP, adenocarcinoma of unknown primary; amp, amplification; cholangio, cholangiocarcinoma; esoph, oesophageal cancer; esthesioneurobl, aesthesioneuroblastoma; fus, fusion; GIST, gastrointestinal stromal tumour; HML, high mutational load (defined here as the sum of all somatic missense variants across the protein-coding region of the tumour genome); HNSCC, head and neck squamous cell carcinoma; HRR, homologous recombination repair; hydradeno., hidradenocarcinoma; IMT, inflammatory myofibroblastic tumour; NEC, neuro-endocrine carcinoma; NSCLC, non-small-cell lung cancer; pre-specified indicates breast, gastric, ovarian, pancreatic, prostate and small-cell lung cancer pre-specified for olaparib. ∗Three cohorts have been closed for enrolment. The dabrafenib + trametinib cohort for NSCLC with BRAF mutation has been closed because this treatment is now registered and reimbursed for this indication. The nivolumab–MSI cohort has completed stage I as well as stage II and is thus closed for further inclusion: the overall clinical benefit rate was 67%. The pembrolizumab cohort of patients with colorectal cancer with a high mutational load (140 to 290) has completed stage I. As no patient experienced clinical benefit, the cohort has been closed and will not be graduated to stage II. All other cohorts with >8 evaluable patients have been graduated to stage II, as clinical benefit was observed once or more in stage I. Treatment Cohorts (incl. tumor type, tumor profile, and number of evaluable/enrolled patients) Axitnib CRC FLT1amp 1/1 Crizotinib Cholangio ALKmut 0/1 CRC METamp 1/1 IMT ALKfus 1/1 Dabrafenib Trametinib NSCLC* BRAFmut 0/1 Dabra-fenib GBM BRAFmut 1/1 UCC BRAFmut 1/1 Lenvatinib Anal FGFR3mut 0/1 Breast FGFR2amp/mut 2/3 CRC FGFR1amp 1/1 CRC FGFR2amp 1/1 NSCLC FGFR1amp 0/1 Sarcoma FGFR1amp 1/1
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