E7386 / Eisai, PRISM Pharma - LARVOL DELTA

E7386 in patients with advanced solid tumors: results from the dose-escalation part and an expansion part of a phase I study. (PubMed, ESMO Open) - "In heavily pretreated patients with advanced solid tumors, E7386 demonstrated a manageable safety profile and a dose-dependent PK profile. PRs were noted in patients with small bowel carcinoma or desmoid tumor."

Journal • P1 data • Colorectal Cancer • Desmoid Tumors • Gastrointestinal Cancer • Oncology • Sarcoma • Small Intestinal Carcinoma • Solid Tumor • APC • KRAS • TP53

Clinical and biomarker results from E7386 study 102: Global dose-expansion cohort of E7386 + lenvatinib (LEN) in patients (pts) with advanced/recurrent endometrial cancer (aEC) that progressed on platinum-based chemotherapy (PBC) and an anti-PD-(L)1 immunotherapy (IO) (ESMO 2025) - P1/2 | "Study 102 dose optimization for E7386 + LEN in pts with aEC is actively enrolling (NCT04008797). Table: 1153P Age, median, yrs (range) 62 (36–76) 1/2/3 prior lines of therapy, n (%) 5 (17)/18 (60)/7 (23) Endometrioid/serous/mixed/clear cell carcinoma/mesonephric adenocarcinoma, n (%) 18 (60)/7 (23)/3 (10)/1 (3)/1 (3) Mismatch repair proficient/deficient/NA, unknown, or missing , n (%) a 16 (53)/7 (23)/7 (23) Serious TEAEs , n (%) 12 (40) ORR/clinical benefit rate , % (95% CI) 33 (17–53)/57 (37–75) DOR/PFS , median, mos (95% CI) 8 (4–9)/6 (3–10) a site-reported"

Biomarker • Clinical • IO biomarker • Metastases • Clear Cell Carcinoma • Endometrial Cancer • Oncology • Oral Cancer • Solid Tumor • CREBBP • CTNNB1 • PIK3CA • POLE • PPP2R1A • PTEN • TP53

Research from Eisai's pipeline includes clinical and biomarker results from Study 102 evaluating E7386, a CREB-binding protein (CBP)/β-catenin interaction inhibitor, in combination with lenvatinib in patients with advanced or recurrent endometrial carcinoma (NCT04008797; Abstract #1153P (Eisai Press Release) - "Eisai highlights breadth of oncology research at ESMO 2025."

Biomarker • P1/2 data • Endometrial Cancer

E7386 enhances lenvatinib's antitumor activity in preclinical models and human hepatocellular carcinoma. (PubMed, Clin Cancer Res) - P1/2 | "E7386 sensitized tumors to lenvatinib, thereby enhancing survival in mice compared with either monotherapy. In patients, E7386 combined with lenvatinib promoted tumor shrinkage and, in parallel, activated ATF4 signaling."

IO biomarker • Journal • Preclinical • Hepatocellular Cancer • Oncology • Solid Tumor • ATF4 • CREBBP • TCF4

Randomized study evaluating optimal dose, efficacy and safety of E7386 + lenvatinib versus treatment of physicians' choice in advanced/recurrent endometrial carcinoma previously treated with anti–PD-(L)1 immunotherapy. (ASCO 2025) - P1/2 | "Patients will be randomized (1:1:1:1) to E7386 120 mg BID + lenvatinib 14 mg QD (n=30); E7386 60 mg BID + lenvatinib 14 mg QD (n=30); lenvatinib 24 mg QD monotherapy (n=30); or treatment of physician's choice (TPC, doxorubicin 60 mg/m2 Q3W or paclitaxel 80 mg/m2 QW [3 weeks on/1 week off]; n=30 in total). This multinational study is actively recruiting. ClinicalTrials.gov number: NCT04008797."

Clinical • Metastases • Endometrial Cancer • Oncology • Solid Tumor • CREBBP • CTNNB1

E7386 study 102: Global dose-expansion cohort of E7386 + lenvatinib (LEN) in patients (pts) with advanced endometrial cancer (aEC) that progressed on platinum-based chemotherapy (chemo) and an anti-PD-(L)1 immunotherapy (IO). (ASCO 2025) - P1/2 | "LEN has antitumor activity in pts with aEC after platinum-based chemo [Vergote 2020] and is approved in combination with pembrolizumab for aEC following prior systemic therapy. E7386 + LEN showed promising antitumor activity with a manageable safety profile in heavily pretreated pts with aEC following platinum-based chemo and IO. The dose-optimization phase of Study 102 for E7386 + LEN in pts with aEC is currently enrolling pts (NCT04008797). aMicrosatellite instability-low (n=3); unknown (n=4); NA (n=1); bas reported by sites; ccirculating tumor DNA analyses were conducted using plasma samples collected at baseline, and were annotated using OncoKB database to identify mutations in TP53; dcomplete response + partial response + stable disease ≥23 wks."

Clinical • IO biomarker • Metastases • Anemia • Endometrial Cancer • Hypertension • Microsatellite Instability • Oncology • Oral Cancer • Renal Disease • Solid Tumor • CREBBP • CTNNB1 • MSI • TP53

Eisai to Present E7386, Co-created by PRISM BioLab and Eisai, at the ASCO (American Society of Clinical Oncology) Annual Meeting (The Manila Times) - P1/2 | N=301 | NCT04008797 | Sponsor: Eisai Inc | "To determine the optimal dose of E7386 in combination with Lenvatinib in the open-label Phase Ib study (NCT04008797), expansion cohort of advanced endometrial cancer patients progressed following platinum-based chemotherapy and anti-PD-(L)1 immunotherapy have been implemented by Eisai and the enrollment of 30 patients was completed. By data cutoff (Oct 22, 2024), with 9 patients remaining on treatment, 30% (9 patients) showed the confirmed response (decrease of tumor size > 30%) for an overall response rate of 30.0%. Furthermore, among patients without prior Lenvatinib treatment, the overall response rate was 42.9%."

P1/2 data • Endometrial Cancer

Eisai Demonstrates Commitment to Oncology Innovation at ASCO 2025 (PRNewswire) - "Notable data include findings from the Phase 3 LEAP-002 study, which evaluated lenvatinib (LENVIMA), the orally available multiple receptor tyrosine kinase inhibitor (TKI) discovered by Eisai, plus pembrolizumab (KEYTRUDA), Merck's anti-PD-1 therapy, versus lenvatinib monotherapy for the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC)....Additional research from Eisai's pipeline will focus on E7386, a CBP/β-catenin interaction inhibitor, in combination with lenvatinib. This includes a dose optimization trial-in-progress presentation (Abstract #TPS5632) and dose expansion findings (Abstract #5599) in patients with advanced or recurrent endometrial carcinoma....An oral presentation will feature data from the final analysis of the Phase 3 LEAP-015 study evaluating lenvatinib plus pembrolizumab and chemotherapy versus chemotherapy in patients with advanced, metastatic gastroesophageal adenocarcinoma."

P1/2 data • P3 data • Trial status • Endometrial Cancer • Gastroesophageal Junction Adenocarcinoma • Hepatocellular Cancer

E7386-J081-102: A Study of E7386 in Combination With Other Anticancer Drug(s) in Participants With Solid Tumor (clinicaltrials.gov) - P1/2 | N=301 | Recruiting | Sponsor: Eisai Inc. | Trial completion date: Nov 2026 ➔ Aug 2027 | Trial primary completion date: Nov 2026 ➔ Aug 2027

Trial completion date • Trial primary completion date • Colorectal Cancer • Endometrial Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • BRAF • EGFR • KRAS • MSI

Randomized study evaluating optimal dose, efficacy, and safety of E7386 plus lenvatinib versus treatment of physician's choice in advanced/recurrent endometrial carcinoma previously treated with platinum-based chemotherapy and immune checkpoint inhibitors. (PubMed, Int J Gynecol Cancer) - P1/2 | "Patients with endometrial carcinoma will be randomized 1:1:1:1 to E7386 120 mg twice daily plus lenvatinib 14 mg once daily, E7386 60 mg twice daily plus lenvatinib 14 mg once daily, lenvatinib 24 mg once daily monotherapy, or treatment of physician's choice (doxorubicin 60 mg/m2 once every 3 weeks or paclitaxel 80 mg/m2 once weekly [3 weeks on/1 week off]). Estimated Dates for Completing Accrual and Presenting Enrollment is expected to take approximately 9 months, with presentation of results in 2026. The trial is registered at ClinicalTrials.gov, NCT04008797."

Checkpoint inhibition • Journal • Endometrial Cancer • Immunology • Oncology • Solid Tumor

E7386 enhances lenvatinib's antitumor efficacy and upregulates ATF4 signalling in preclinical models and human hepatocellular carcinoma (EASL 2025) - P1/2 | "The combination of E7386 and lenvatinib enhanced survival in mice and achieved anti- tumor responses in patients. Mechanistically, E7386 induced ATF4-dependent ISR, thereby potentially altering protein synthesis, reducing cyclin levels and limiting cell cycle progression. E7386 potentiated the antiangiogenic effects of lenvatinib, resulting in reduced angiogenesis, contributing to extended survival in mice and enhanced antitumor activity compared with either monotherapy."

IO biomarker • Preclinical • Hepatocellular Cancer • Oncology • Solid Tumor • ATF4 • CD31 • CREBBP • PECAM1 • TCF4

TIP25-243: Randomized Study Evaluating Optimal Dose, Efficacy and Safety of E7386 + Lenvatinib Versus Treatment of Physicians' Choice in Advance/Recurrent Endometrial Carcinoma Previously Treated With Anti-PD-(L)1 Immunotherapy. (PubMed, J Natl Compr Canc Netw) - No abstract available

Journal • Endometrial Cancer • Oncology • Solid Tumor

Randomized Study Evaluating Optimal Dose, Efficacy And Safety Of E7386 + Lenvatinib Versus Treatment Of Physicians' Choice In Advanced/Recurrent Endometrial Carcinoma Previously Treated With Anti-PD-(L)1 Immunotherapy (ESGO 2025) - P1/2 | "Up to 3 prior lines of therapy, regardless of setting, are allowed; prior hormonal therapy and radiation do not count as lines of therapy.Patients will be randomized (1:1:1:1) to E7386 120 mg BID + lenvatinib 14 mg QD (n=30); E7386 60 mg BID + lenvatinib 14 mg QD (n=30); lenvatinib 24 mg QD monotherapy (n=30); or treatment of physician's choice (TPC, doxorubicin 60 mg/m2 Q3W or paclitaxel 80 mg/m2 QW [3 weeks on/1 week off]; n=30 in total). Adverse events will be monitored and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.Results n/a Conclusion This multinational study is actively recruiting. ClinicalTrials.gov number: NCT04008797"

Clinical • Metastases • Endometrial Cancer • Oncology • Solid Tumor • CREBBP • CTNNB1

A Study of E7386 in Participants With Advanced Solid Tumor Including Colorectal Cancer (CRC) (clinicaltrials.gov) - P1 | N=70 | Active, not recruiting | Sponsor: Eisai Co., Ltd. | Trial completion date: Jan 2025 ➔ Jan 2026 | Trial primary completion date: Jan 2025 ➔ Jan 2026

Trial completion date • Trial primary completion date • Adrenal Cortex Carcinoma • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatocellular Cancer • Oncology • Solid Tumor • APC • AXIN1 • RNF43 • ZNRF3

KEYNOTE-C83: A Study of E7386 in Combination With Pembrolizumab in Previously Treated Participants With Selected Solid Tumors (clinicaltrials.gov) - P1/2 | N=89 | Completed | Sponsor: Eisai Inc. | Active, not recruiting ➔ Completed

Trial completion • Colorectal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor • BRAF

E7386 enhances both lenvatinib and anti-PD1 antitumor activity in HCC (EORTC-NCI-AACR 2024) - P1/2 | "In Conclusion, E7386 exerts antitumor activity by limiting the cell cycle via the induction of mTORC1/ATF4 signaling in vitro, as well as sensitizing HCC to anti-angiogenesis, in CTNNB1-mutant mouse models. Furthermore, the combination of E7386 and lenvatinib enhanced survival in vivo, which was further increased by the triplet combination with anti-PD1."

IO biomarker • Hepatocellular Cancer • Oncology • ATF4 • CREBBP • TCF4

DOSE-EXPANSION PART OF A PHASE 1B GLOBAL STUDY OF E7386 PLUS LENVATINIB IN PATIENTS WITH HEPATOCELLULAR CARCINOMA AND OTHER SOLID TUMORS INCLUDING ENDOMETRIAL CANCER (IGCS 2024) - "The protocol is being amended to assess the optimal dose of E7386 when used in combination with lenvatinib, and the efficacy of E7386+lenvatinib relative to treatment of physician's choice, and lenvatinib monotherapy, in patients with advanced EC and progression following anti-PD(L)1 therapy. Current Trial Status: As of June 28, 2024, 61 patients with HCC and 30 patients with EC have enrolled; dose optimization and regional expansion in EC is planned."

Clinical • P1 data • Endometrial Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Global, phase Ib dose-expansion cohort of E7386 + lenvatinib (LEN) in patients (pts) with advanced (a) endometrial cancer (EC) that progressed on platinum-based chemotherapy (CTx) and an anti-PD-(L)1 immunotherapy (IO) (ESMO 2024) - P1 | "LEN + pembrolizumab is an approved therapy for pts with aEC after systemic therapy in any setting. E7386 + LEN has shown promising preliminary antitumor activity with a manageable safety profile. Enrollment to the expansion part of Study 102 is ongoing. Table: 738P aNone had received LEN as prior therapy."

Clinical • Metastases • P1 data • Endometrial Cancer • Oncology • Oral Cancer • Solid Tumor

E7386-J081-102: A Study of E7386 in Combination With Other Anticancer Drug(s) in Participants With Solid Tumor (clinicaltrials.gov) - P1/2 | N=301 | Recruiting | Sponsor: Eisai Inc. | Phase classification: P1 ➔ P1/2 | N=181 ➔ 301 | Trial completion date: Mar 2027 ➔ Nov 2026 | Trial primary completion date: Mar 2027 ➔ Nov 2026

Combination therapy • Enrollment change • Phase classification • Trial completion date • Trial primary completion date • Colorectal Cancer • Endometrial Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • BRAF • EGFR • KRAS • MSI

Eisai to Present E7386, co-created by PRISM BioLab and Eisai, at the ESMO (European Society for Medical Oncology) Annual Meeting (PRNewswire) - P1b | N=181 | NCT04008797 | Sponsor: Eisai Inc. | "PRISM BioLab...announced that the interim analysis of a combination study of E7386, created through collaboration research with Eisai Co., Ltd. ('Eisai'), and Lenvatinib mesylate ('lenvatinib') will be presented by Eisai at the European Society for Medical Oncology (ESMO) Congress 2024....By data cutoff (Mar 7, 2024) in 16 patients, 31% (5 patients) showed the confirmed partial response (decrease of tumor size > 30%), and 31% (5 patients) showed the stable disease (tumor size -30% to +20%). These results confirmed promising preliminary antitumor activity of E7386 + Lenvatinib with a manageable safety profile. To complete the study, enrollment to the expansion part is ongoing."

P1 data • Endometrial Cancer

Eisai Accelerates Progress in Oncology Research with New Data at ESMO Congress 2024… (PRNewswire) - "Research from Eisai's pipeline includes a quality-of-life analysis from the Phase 3 EMERALD study in Japan evaluating either Eisai's eribulin mesylate (HALAVEN) or a taxane in combination with trastuzumab and pertuzumab in patients with HER2-positive, locally advanced or metastatic breast cancer (NCT03264547; Presentation: #373P); findings from a Phase 1b dose-expansion cohort evaluating E7386 (a CBP/β-catenin interaction inhibitor) in combination with lenvatinib in patients with advanced endometrial carcinoma with progression following prior anti-PD-(L)1 immunotherapy and platinum-based chemotherapy (NCT04008797; Presentation: #738P); as well as presentations for BB-1701...in previously-treated patients with HER2-positive or HER2-low unresectable or metastatic breast cancer (NCT06188559; Presentation: #437TiP) and non-small cell lung cancer patients with HER2 mutation/amplification (Presentation: #1296P; presented by Bliss Biopharmaceutical Co., Ltd), respectively."

Clinical data • Endometrial Cancer • HER2 Positive Breast Cancer • Non Small Cell Lung Cancer

KEYNOTE-C83: A Study of E7386 in Combination With Pembrolizumab in Previously Treated Participants With Selected Solid Tumors (clinicaltrials.gov) - P1/2 | N=89 | Active, not recruiting | Sponsor: Eisai Inc. | Trial completion date: Sep 2025 ➔ Nov 2024 | Trial primary completion date: Sep 2025 ➔ Nov 2024

Combination therapy • Trial completion date • Trial primary completion date • Colorectal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor • BRAF

KEYNOTE-C83: A Study of E7386 in Combination With Pembrolizumab in Previously Treated Participants With Selected Solid Tumors (clinicaltrials.gov) - P1/2 | N=89 | Active, not recruiting | Sponsor: Eisai Inc. | Recruiting ➔ Active, not recruiting | N=156 ➔ 89

Combination therapy • Enrollment change • Enrollment closed • Colorectal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor • BRAF

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). (ASCO 2024) - P1 | "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 • Combination therapy • P1 data • Endometrial Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CREBBP

Study of E7386 in Participants With Selected Advanced Neoplasms (clinicaltrials.gov) - P1 | N=60 | Active, not recruiting | Sponsor: Eisai Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: May 2024 ➔ Mar 2026 | Trial primary completion date: May 2024 ➔ Mar 2026

Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Endometrial Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Oncology • Ovarian Cancer • Thyroid Gland Carcinoma • CTNNB1