E7386 / Eisai, PRISM Pharma - LARVOL DELTA

A phase 1 study of E7386, a CREB-binding protein (CBP)/β-catenin interaction inhibitor, in patients (pts) with advanced solid tumors including colorectal cancer: Updated dose-escalation part. (ASCO-GI 2023) - P1 | "E7386 120 mg BID was tolerated and determined as the recommended dose for the expansion part. Based on additional analyses of the dose-escalation part of this study, further investigation of safety, preliminary efficacy, PK, and biomarker analyses of E7386 is ongoing using 2 dose levels (100 and 120 mg BID) in the expansion part. Clinical trial information: NCT03833700."

Clinical • Metastases • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Small Intestinal Carcinoma • Solid Tumor • APC • CREBBP • CTNNB1 • FGF21

E7386 + Lenvima: Topline data from P1b/2 trial (NCT04008797) for solid tumors FY2026 (Eisai) - Q1 FY2026 Results

P1/2 data • Oncology • Solid Tumor

Establishment of a craniopharyngioma organoid model for identifying novel therapeutic targets (ISPNO 2026) - "Treatment of adamantinomatous craniopharyngioma organoid models with E-7386, an inhibitor of the WNT/β-catenin signaling pathway, significantly suppressed organoid growth. In conclusion, we successfully established patient-derived organoid models of craniopharyngioma. These organoid models are applicable to drug testing and are expected to be useful for the development of novel therapeutic strategies and for detailed analyses of the molecular mechanisms underlying tumor growth."

Brain Cancer • CNS Tumor • BRAF

A first-in-human, open-label multicentre Phase 1 study of the orally administered E7386 in patients with selected advanced neoplasms. (PubMed, Br J Cancer) - P1 | "E7386 demonstrated a manageable safety profile, a dose-dependent pharmacokinetic profile, and some disease stabilisation in heavily pretreated patients with advanced solid tumours."

First-in-human • Journal • P1 data • Hepatocellular Cancer • Oncology • Solid Tumor • CTNNB1

Leveraging E7386 phase 1 trials for cardiac safety: Gaining concentration-QTc insights to inform early-stage oncology development. (ASCO 2026) - P1 | "Phase 1 C-QTc evaluations of E7386 offer critical insights on cardiac safety that inform dose selection and monitoring strategies for further clinical development. The predicted mean ΔQTcF and its 90% CI upper bound remained below 10 ms for concentrations up to 2650 ng/mL, based on C-QTc analysis of two phase 1 studies. No significant cardiac safety concerns were identified at the studied dose levels."

Clinical • P1 data • Oral Cancer • Solid Tumor • CREBBP • CTNNB1

Additional research from Eisai’s pipeline includes an online publication highlighting analyses from Phase 1 trials evaluating E7386, a CREB-binding protein (CBP)/β-catenin interaction inhibitor, to inform cardiac safety assessments in early-stage oncology development (Abstract #e24005). (Streetinsider.com)

P1 data • Adrenal Cortex Carcinoma • Colorectal Cancer • Desmoid Tumors • Head and Neck Cancer • Hepatocellular Cancer • Melanoma • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Small Bowel Adenocarcinoma • Thyroid Gland Anaplastic Carcinoma

A Phase 1 Oral Mass Balance and Combined Intravenous [14C] Microtracer Study to Characterize the Absorption, Metabolism, Excretion, and Pharmacokinetics of Antitumor Drug E7386 in Humans. (PubMed, J Clin Pharmacol) - "These results suggest that [14C]E7386-related material is predominantly excreted in feces after oral administration. Overall, IV administration and oral administration of a single E7386 dose was tolerable in healthy participants, and adverse events were manageable."

Clinical • Journal • P1 data • PK/PD data • Oncology • CREBBP

Antitumor and antiangiogenic activities of E7386 in combination with lenvatinib in human endometrial carcinoma xenograft models (AACR 2026) - P1/2 | "These results suggest that the combination of E7386 with LEN exerted enhanced antiangiogenic activity against tumor microvessels compared with LEN-alone, and demonstrated potent antitumor activity in preclinical EC xenograft models."

Combination therapy • Preclinical • Endometrial Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CREBBP • CTNNB1 • PECAM1

E7386, a Wnt/β-catenin signaling modulator, suppresses the differentiation of regulatory T cells in combination with lenvatinib plus anti-PD-1 antibody (AACR 2024) - "In summary, these data suggest a suppressive role of E7386 on Treg differentiation, which leads to antitumor activity of E7386 in combination with lenvatinib and anti-PD-1 antibody in a preclinical tumor model."

Combination therapy • IO biomarker • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CD8 • CREBBP • FOXP3 • IL2 • PTPRC • STAT5 • TGFB1

Single-cell RNA-sequencing analysis of tumor endothelial cells reveals suppression of specific endothelial subtypes by the combination treatment of Wnt/β-catenin signaling modulator E7386 plus lenvatinib (AACR 2024) - P1/2 | "Taken together, these results suggest a role for E7386 in suppressing the activation of Wnt/β-catenin signaling induced by LEN monotreatment in specific EC subtypes; this activity leads to enhanced antiangiogenic and antitumor activity with E7386 plus LEN combination therapy in a preclinical tumor model."

Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CD31 • CREBBP • PECAM1 • PTPRC

Targeting epigenetic activity of beta-catenin/CBP impedes oral cancer progression (AACR 2024) - "Evaluation of tumor tissues by immunofluorescence revealed statistically significant decreases in Cbp, H3K4me3, Keratin 14, and Podoplanin expression in response to E7386 alone and in combination with anti PD-1. Collectively our results suggest that a combination therapy comprising anti PD-1 treatment with E7386-targeting β-catenin/CBP epigenetic signaling is likely to impede OSCC evolution to advanced disease."

IO biomarker • Late-breaking abstract • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • Tongue Carcinoma • KRT14 • PDPN

Study of E7386 in Participants With Selected Advanced Neoplasms (clinicaltrials.gov) - P1 | N=60 | Active, not recruiting | Sponsor: Eisai Inc. | Trial completion date: Mar 2026 ➔ Mar 2027 | Trial primary completion date: Mar 2026 ➔ Mar 2027

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

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 | Active, not recruiting | Sponsor: Eisai Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Aug 2027 ➔ Mar 2027 | Trial primary completion date: Aug 2027 ➔ Mar 2027

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

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 2026 ➔ Mar 2027 | Trial primary completion date: Jan 2026 ➔ Mar 2027

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

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