Dose-expansion part of a phase 1b global study of E7386 in combination with lenvatinib (LEN) in patients (pts) with hepatocellular carcinoma (HCC) and other solid tumors including endometrial cancer (EC).

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TPS3169 Background: E7386, a first-in-class anticancer agent, inhibits protein-protein interaction between β-catenin and the CREB-binding protein, thus modulating Wnt/β-catenin signaling. E7386 is being tested in combination with LEN in the open-label global phase 1b Study 102. The dose-escalation part of Study 102 determined the recommended dose of E7386 + LEN in pts with HCC and other solid tumors. Here we describe the ongoing dose-expansion part in pts with HCC or EC. Methods: Eligible pts ≥18 years old should have an ECOG PS of 0-1 and a confirmed diagnosis of advanced, unresectable, or recurrent solid tumor. Pts with HCC will have a Child-Pugh score of A and a categorization of BCLC Stage B (not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment) or Stage C. Pts with HCC should also have received 1 prior immuno-oncology (IO)-based regimen and have progressed on/after prior treatment with IO therapy. If ineligible for IO therapy, pts should not have received prior systemic therapy; pts who previously received LEN are ineligible. In the EC subpart, pts should have disease progression after receiving prior platinum-based chemotherapy (PBT) and an IO-based therapy for EC. Pts may have received 1 additional line of PBT if given in the neoadjuvant/adjuvant setting, but not exceeding 3 lines of therapies. Pts with EC who are ineligible for IO therapy may have received only 1 prior systemic therapy including PBT. Pts who have received prior LEN therapy will be eligible if they meet protocol-specified criteria. Pts with HCC (n≈60) will be randomized in a 2:1 ratio into 1 of 2 treatment arms and will receive either the combination E7386 + LEN or LEN monotherapy in 28-day cycles. E7386 will be administered at 100 mg BID in the combination arm and LEN will be administered QD at 8 mg (if body weight <60 kg) or 12 mg (if body weight ≥60 kg) in both arms. Pts with HCC will be stratified by geographical region (Western Europe and North America vs Japan vs other countries). Pts with EC (n≈30) will receive only the combination E7386 120 mg BID + LEN 14 mg QD. The expansion part of Study 102 aims to assess safety and tolerability (primary endpoints), and pharmacokinetics and preliminary efficacy (secondary endpoints), of E7386 in combination with LEN for pts with HCC and EC. Efficacy of LEN monotherapy will be assessed for HCC (secondary endpoint). Tumors will be assessed by investigator per RECIST v1.1 every 8 weeks from the date of the first dose. Adverse events will be monitored and recorded for up to 30 days after the last dose or until initiation of a new anticancer therapy, whichever occurs first. Study sites will include the United States, France, Republic of Korea, Japan, and Taiwan. As of February 5, 2024, 46 pts with HCC and 16 pts with EC have enrolled. Clinical trial information: NCT04008797 .