3131 Background: Human epidermal growth factor receptor 2 (HER2) gene amplification or mutations have emerged as oncogenic drivers and therapeutic targets not limited to breast and gastric cancers, but also in a variety of cancers. Despite its considerable therapeutic potential, the evidence has not been established. To address this unmet need, we conducted an organ-agnostic basket trial targeting HER2-amplified solid tumors. Methods: JUPITER is a multicenter, single-arm, phase 2 basket trial for solid tumor patients (pts) with HER2 amplification determined by next-generation sequencing (NGS). Both tissue and liquid NGS results were allowed. HER2 amplification by ISH or HER2 overexpression by IHC were not used for inclusion. Pts had treatment-refractory metastatic tumors, or rare cancers without established standard of care. Breast, gastric, and colorectal cancers were excluded. Pts were treated with intravenous trastuzumab (8 mg/kg loading dose followed by 6 mg/kg) and pertuzumab (840 mg loading dose followed by 420 mg) every 3 weeks until disease progression or any other reason for discontinuation. Tumor response was assessed using RECIST v1.1. Primary endpoint was ORR by blinded independent central review (BICR), and secondary endpoints were ORR assessed by the investigators, progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety. We set the ORR threshold 5% and expected ORR was 20%. Estimated sample size was 38 patients with one-sided alpha 2.5% and power 80%. Results: Between April 2019 and June 2020, 42 pts were consented, and 40 pts were treated. Median age was 62 (range, 21-86) and 60% were females. The most common diagnosis was biliary tract cancer (20%), followed by salivary ductal carcinoma (12.5%) and endometrial cancer (12.5%). At data cutoff (1 Sep 2021), ORR by BICR was 22.5% (95%CI: 10.8%-38.5%). ORR assessed by the investigator was 25% (95%CI: 12.7%-41.2%). PFS, OS and DOR were not reached at data cutoff; 3 responders remained on treatment. Of 40 pts, 32.5% had grade ≥ 3 adverse events; 10% were treatment-related, including neutropenia, hypertension, peripheral sensory neuropathy and lymphoedema (all grade 3). No treatment-related death was observed. Exploratory biomarker analysis of response and resistance is in progress. Conclusions: Combination therapy with trastuzumab and pertuzumab was well tolerated and showed promising efficacy for the patients with HER2-amplified solid tumors determined by NGS. Clinical trial information: jRCT2031180150.

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3111 Background: Precision oncology using the comprehensive genomic profiling (CGP) test by next-generation sequencing has been introduced into clinical practice. In Japan, only 6.8% of patients accessed the precision treatment because it is only indicated after standard of care (SoC). FoundationOne CDx (F1CDx) is the software as a medical device for the detection of actionable and druggable genomic alterations in 324 genes. F1CDx has the function of both CGP test and companion diagnostics (CDx). Therefore, F1CDx could be ideally used in the early stages of treatments. In this study, we investigated the clinical utility of F1CDx in previously untreated patients with metastatic or recurrent solid tumors. Methods: We conducted a multi-institutional, prospective study in six hospitals in Japan (FIRST-Dx study). Chemotherapy-naïve adult patients with advanced solid tumor (GI, Lung, Breast, GYN, Melanoma) and ECOG performance status of 0-1 were enrolled. Primary endpoint was the ratio of patients with actionable mutation. Secondary endpoints were the ratio of patients with druggable mutation, molecular-based recommended therapy (MBRT), gene alteration with CDx, CGP success rate, and patients who actually received MBRT. Results: 183 patients were enrolled between May 2021 and February 2022, 180 patients with median (range) age 64 (23-88) years underwent F1CDx test (92 men, lung [n=28], colon/small intestine [n=27], pancreas [n=27], breast [n=25], biliary tract [n=20], gastric [n=19], uterus [n=12], esophagus [n=10], ovary [n=6], and skin melanoma [n=6]). 175 tests were successful (CGP success rate: 97%), and 172 patients were evaluable for endpoint analyses with follow-up through July 2022. Actionable and druggable cancer genomic alterations were found in 172 patients (100.0% [95% CI: 97.9-100.0%]) and 109 patients (63.4% [95% CI: 55.7-70.6%]), respectively. MBRT determined by molecular tumor board was found in 105 patients (61.0% [95% CI: 53.3-68.4%]). Genomic alterations included in the CDx list of F1CDx were found in 49 patients (28.5% [95%CI: 21.9-35.9%]) in the tumor-agnostic setting. After a median follow-up of 7.9 months, 34 patients (19.8 % [95%CI: 14.1-26.5%]) actually received MBRTs. Twenty-six patients received evidence level A MBRT, two received evidence level B MBRT, and six received evidence level C MBRT. Conclusions: We showed that 61% of the patients with previously untreated advanced cancer had MBRTs found by F1CDx and 20% of them actually received MBRTs early in their disease course. CGP test before SoC for advanced solid tumors could provide better opportunities for receiving MBRTs than after completion of SoC. Our data would recommend expanded approval with respect to the timing of CGP test for patients with previously untreated advanced solid tumors. Clinical trial information: UMIN000042408 .