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LBA3506 Background: Patients (pts) with initially unresectable CRLM may qualify for curative-intent local therapy after downsizing by induction systemic therapy. The CAIRO5 study aims to find the optimal induction regimen. We present the results of pts with right-sided and/or RAS/ BRAFV600E mutated primary tumors. Accrual in pts with left-sided and RAS/ BRAFV600E wildtype tumors is ongoing. Methods: Pts were randomized between FOLFOX or FOLFIRI + bevacizumab (B) (arm A) and FOLFOXIRI-B (arm B), in both arms up to 12 cycles and followed by 5FU/LV/B maintenance. Prior systemic or local therapy for metastases was not allowed. Unresectability of CRLM at baseline was assessed by an online liver expert panel of surgeons and radiologists based on predefined criteria, and resectability every 2 months thereafter based on panel majority vote. The primary endpoint was progression-free survival (PFS). Secondary endpoints were R0/1 resection, overall survival, overall response rate (ORR), toxicity, pathologic response, postoperative morbidity and correlation of panel evaluations with outcome. Pts were stratified by potentially resectable vs permanently unresectable CRLM, serum LDH (normal/abnormal), BRAFV600E mutation, sidedness, choice of irinotecan vs oxaliplatin and institute. To detect a hazard ratio (HR) of 0.70 for PFS with 80% power and a 2-sided log-rank test at 5%, 257 events were required, assuming a median PFS of 8.7 months for arm A. Results: From December 2014 until March 2021, 294 pts were randomized, 148 in arm A and 146 in arm B in 43 Dutch and 1 Belgian sites. 3 ineligible pts were excluded. Median follow up was 40 months. Pts received a median of 10 vs 9 induction cycles in arm A vs B. Main characteristics were (arm A/B): median age 61/65 years, male 63.9/60.4%, right-sided primary tumor 39.5/41.7%, RAS mutant 85.7/86.1%, BRAFV600E mutant 6.8/8.3%, synchronous disease 86.4/89.6%, prior adjuvant chemotherapy 4.8/4.9%, median number of CRLM 12/12. With 259 events, median PFS in arm A vs B was 9.0 vs 10.6 months (stratified HR 0.74, 95% CI 0.57-0.96, p=0.02). ORR was 32.0% vs 52.1% (p

5516 Background: Ovarian cancer is globally the second most common cause of death among women with gynecologic malignancies. Despite high initial response rates, the overall prognosis of this patient population remains poor. The majority of advanced ovarian cancers will become platinum resistant defined by recurrence within six months after completion of platinum therapy. In the first part of the current phase II study, the combination of carboplatin and the Wee1 inhibitor adavosertib (AZD1775), showed to be safe and effective in patients with TP53 mutated platinum resistant ovarian cancer. The aim of this additional cohort is to gain more information about the safety and efficacy of the combination and to explore predictive biomarkers for resistance and response to adavosertib. Methods: In this additional cohort 29 evaluable were treated with carboplatin AUC 5 mg/ ml·min and adavosertib 225 mg BID for 2.5 days in a 21-day cycle. The anti-tumor activity was assessed according to RECIST 1.1. Pre-, on- and post-treatment biopsies were obtained to explore genetic determinants of drug resistance and response to adavosertib. Results: A total of 32 patients with a median age of 62 years (39-77 years) were enrolled in this cohort. All patients had carboplatin/paclitaxel as first line therapy. Six patients received a second-line non-platinum containing regimen. Median platinum free interval was 5.8 months (range 1.7 – 11.9). Twenty-nine patients were evaluable for efficacy. Grade 1-2 bone marrow toxicity, nausea, vomiting and fatigue were the most common adverse events. Dose reductions of carboplatin and/or adavosertib were made in 15/29 evaluable patients (52%). Dose delays occurred in the majority of patients (76%), mostly due to neutropenia and thrombocytopenia. Twelve patients showed PR as best response, resulting in an ORR of 38% in the intention-to-treat population (95% CI 21%-56%). The median PFS was 5.6 months (range 1.1-32 months, 95% CI 4.2-7.0) and median duration of response was 5.3 months (95% CI 0.13-10.5). Conclusions: Adavosertib 225 mg BID for 2.5 days and carboplatin AUC 5 in a 21-day cycle could be safely combined and shows promising anti-tumor efficacy in patients with platinum resistant ovarian cancer. Bone marrow toxicity remains the most common reason for dose reductions and dose delays. Translational biomarker results (CCNE1 analysis as potential predictive marker for response and resistance and WGS) to better understand the anti-tumor activity of the combination are pending. Clinical trial information: NCT01164995.