Lenvima (lenvatinib) / Eisai, Merck (MSD), Knight Therap - LARVOL DELTA

Pembrolizumab plus lenvatinib as second-line treatment in patients with pleural mesothelioma (PEMMELA): cohort 2 of a single-arm, phase 2 study. (PubMed, Lancet Oncol) - P2 | "This study met its primary endpoint, showing high clinical activity of pembrolizumab plus lenvatinib, but with substantial toxicity, in patients with pleural mesothelioma who had progressed after first-line nivolumab plus ipilimumab. This drug combination is promising for future studies in pleural mesothelioma."

Journal • P2 data • Cardiovascular • Fatigue • Hypertension • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Pleural Mesothelioma • Solid Tumor

Nivolumab plus ipilimumab vs lenvatinib or sorafenib as first-line treatment for unresectable hepatocellular carcinoma (HCC): 4-year follow-up of CheckMate 9DW. (ASCO-GI 2026) - P3 | "After 4 years of follow-up, 1L NIVO + IPI continued to show sustained efficacy benefit vs LEN/SOR in unresectable HCC and manageable safety with no new concerns. These results continue to support NIVO + IPI as a standard-of-care treatment in these patients. aPer BICR."

Clinical • Late-breaking abstract • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Belzutifan (bel) plus lenvatinib (lenva) versus cabozantinib (cabo) for advanced renal cell carcinoma (RCC) after anti–PD-(L)1 therapy: Open-label phase 3 LITESPARK-011 study. (ASCO-GU 2026) - P3 | "Clinical Trial Registry Number: NCT04586231. The full, final text of this abstract will be available on Feb 28 at 10:00 AM EST."

Clinical • Late-breaking abstract • Metastases • P3 data • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Nivolumab plus ipilimumab versus lenvatinib or sorafenib as first-line treatment for unresectable hepatocellular carcinoma: A cost-effectiveness analysis. (PubMed, Cancer) - "Nivolumab plus ipilimumab is unlikely to be cost-effective as first-line therapy for unresectable HCC from US health care payer perspective. However, extended dosing interval or price reductions may render the regimen economically viable, with important implications for clinical practice, payers, and policy."

Clinical • HEOR • Journal • Hepatocellular Cancer • Oncology • Solid Tumor

Efficacy and safety of pembrolizumab, lenvatinib, and reduced-dose gemcitabine/oxaliplatin as initial treatment for advanced biliary tract cancer: a multicenter, single-arm, prospective, phase II study. (PubMed, J Immunother Cancer) - "Pembrolizumab plus lenvatinib with reduced-dose GEMOX demonstrated promising efficacy and a favorable safety profile in advanced BTC, suggesting that chemotherapy de-escalation may optimize the efficacy-toxicity balance. Further randomized studies are warranted to confirm these findings and refine biomarker-based treatment selections."

IO biomarker • Journal • P2 data • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor • CA 19-9 • CEACAM5

Lenvatinib plus pembrolizumab and chemotherapy versus chemotherapy in advanced, metastatic gastroesophageal adenocarcinoma: The phase 3, randomized LEAP-015 study. (ASCO 2025) - P3 | "All pts were randomly assigned 1:1 to induction with pembrolizumab 400 mg IV Q6W (x2) plus oral lenvatinib 8 mg QD and investigators choice chemotherapy (CAPOX Q3W x4 or mFOLFOX6 Q2W x6) then consolidation with pembrolizumab 400 mg Q6W for ≤16 doses plus lenvatinib 20 mg QD (only if 8 mg tolerated for at least 3 weeks), or chemotherapy alone (CAPOX or FOLFOX)... Pembrolizumab plus lenvatinib and chemotherapy vs chemotherapy provided statistically significant improvement in PFS and ORR in pts with advanced unresectable or metastatic gastroesophageal carcinoma at interim analysis. However, there was no significant improvement in OS in pts with PD-L1 CPS ≥1 at final analysis. Safety profiles were consistent with known regimens, with higher AE rates seen in pts receiving the experimental treatment."

Clinical • Metastases • P3 data • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Oncology • Solid Tumor • HER-2

Lenvatinib Plus Pembrolizumab and Chemotherapy Versus Chemotherapy in Advanced Metastatic Gastroesophageal Adenocarcinoma: The Phase III, Randomized LEAP-015 Study. (PubMed, J Clin Oncol) - P3 | "Lenvatinib plus pembrolizumab and chemotherapy versus chemotherapy provided a statistically significant improvement in PFS in advanced unresectable or metastatic gastroesophageal carcinoma at interim analysis although the clinical significance of this difference seems to be limited. No significant improvement occurred in OS in participants with PD-L1 CPS ≥1."

Journal • P3 data • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Oncology • Solid Tumor • HER-2

Conversion therapy of tislelizumab plus lenvatinib and GEMOX in unresectable locally advanced biliary tract cancer (ZSAB-TransGOLP): a multicentre, prospective, phase 2 study. (PubMed, Lancet Oncol) - P2 | "With promising efficacy and manageable safety, GOLP represents a potentially feasible and high-efficiency conversion regimen for unresectable locally advanced biliary tract cancer."

Journal • P2 data • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gallbladder Cancer • Hematological Disorders • Neutropenia • Oncology • Solid Tumor

Lenvatinib plus pembrolizumab in pretreated metastatic B3 thymoma and thymic carcinoma (PECATI): a single-arm, phase 2 trial. (PubMed, Lancet Oncol) - P2 | "Lenvatinib combined with pembrolizumab showed potential as a standard treatment for pretreated advanced B3 thymoma and thymic carcinoma. Although the toxicity profile appeared manageable, close monitoring for toxicity is advised."

Journal • P2 data • Cardiovascular • CNS Disorders • Endocrine Disorders • Fatigue • Gastroenterology • Gastrointestinal Disorder • Immunology • Oncology • Pneumonia • Solid Tumor • Thymic Carcinoma • Thymoma • Thymus Cancer

First-line pembrolizumab-based regimens for advanced clear cell renal cell carcinoma: KEYMAKER-U03 substudy 03A (ESMO 2025) - P1/2 | "Methods Adults with advanced ccRCC and no prior systemic therapy were randomized 2:1 to open investigational arms or the reference (ref): coformulated quavonlimab (qmab; anti-CTLA-4)/pembro + lenvatinib (lenva; VEGFR-TKI); coformulated favezelimab (fave; anti-LAG-3)/pembro + lenva; pembro + lenva + belzutifan (bel; HIF-2α inhibitor); coformulated vibostolimab (vibo; anti-TIGIT)/pembro + bel; ref, pembro + lenva. Other regimens did not show improved ORR and PFS compared with pembrolizumab + lenvatinib, yet the duration of follow-up was insufficient to detect long-term contributions to OS. Safety profiles were consistent with the profiles of the individual drugs in each regimen."

Clinical • Late-breaking abstract • Metastases • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • EPAS1 • TIGIT

Lenvatinib plus pembrolizumab and chemotherapy vs pembrolizumab and chemotherapy in untreated metastatic esophageal squamous cell carcinoma: The randomized phase III LEAP-014 study (ESMO 2025) - P3 | "All pts were randomized 1:1 to induction with len 8 mg PO QD + pembro 400 mg IV (Q6W x2) + chemo (FP [Q3W x4] or mFOLFOX6 [Q2W x6] or TP [Q3W x4 in East Asia, excluding Japan]) for 12 weeks followed by consolidation with len 20 mg PO QD (if initial len 8 mg PO QD dose was tolerated) + pembro 400 mg IV Q6W for up to 16 doses (arm 1) or to pembro + chemo (FP, mFOLFOX6, or TP [arm 2])...Conclusions Lenvatinib + pembrolizumab + chemo vs pembrolizumab + chemo did not result in significant improvement in OS as first-line therapy in pts with mESCC. No new safety signals were observed."

Clinical • Late-breaking abstract • Metastases • P3 data • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Oncology • Squamous Cell Carcinoma • PD-L1

NRG GY012: A randomized phase II study comparing single-agent cediranib with olaparib/durvalumab, cediranib/durvalumab, and olaparib/capivasertib in women with recurrent, persistent or metastatic endometrial cancer (ESMO 2025) - P2 | "Methods Eligible patients (pts) had at least 1 prior line of chemotherapy (no more than 2) with prior endocrine and immunotherapy (prior lenvatinib/pembrolizumab excluded) allowed, ECOG 0-1. Conclusions The combinations of O+D, O+CA and C+D did not meet prespecified endpoints for significance in an unselected population. Further evaluation of molecular subgroups and prior immunotherapy treatment is necessary to determine if there are any signals warranting future investigation."

Clinical • Metastases • P2 data • Endometrial Cancer • Oncology • Solid Tumor

A multicenter randomized phase II trial of lenvatinib plus everolimus versus cabozantinib in patients with metastatic clear cell RCC that progressed on PD-1 immune checkpoint inhibition (LenCabo). (PubMed, Ann Oncol) - "In this randomized phase II trial in metastatic ccRCC that progressed on prior PD-1 ICIs, lenvatinib + everolimus significantly prolonged PFS over cabozantinib. As the first head-to-head comparison of contemporary second-line or later treatments after ICI, these results are relevant to treatment sequencing and inform oncology practice."

Checkpoint inhibition • Journal • P2 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Overall efficacy outcomes of nivolumab plus ipilimumab by occurrence of immune-mediated adverse events (IMAEs) and additional safety from Asian patients in CheckMate 9DW (ESMO Asia 2025) - P3 | "Background: In the phase 3 CheckMate 9DW trial, at a median follow-up of 35.2 months (mo), first-line nivolumab + ipilimumab (NIVO + IPI) showed significant overall survival (OS) benefit (median, 23.7 mo vs 20.6 mo; HR, 0.79 [95% CI, 0.65–0.96; P = 0.018]), higher objective response rate (ORR; 36% vs 13%; P < 0.0001) by blinded independent central review (BICR), and manageable safety vs lenvatinib (LEN) or sorafenib (SOR) in patients (pts) with unresectable hepatocellular carcinoma (uHCC). NIVO + IPI showed durable responses and long-term survival benefit regardless of IMAEs. IMAEs in Asian pts treated with NIVO + IPI occurred early and were manageable, consistent with the overall population. These results further support NIVO + IPI as a standard of care in uHCC."

Adverse events • Clinical • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology

Exploring the crosstalk between the FGF/FGFR pathway and tumor microenvironment in clear cell renal cell carcinoma. (PubMed, PLoS One) - "This study provides the first comprehensive evaluation of FGFR1-4 expression in ccRCC and suggests that FGFR1 expression may contribute to the immunosuppressive tumor microenvironment by recruiting TAM. These findings indicate that FGFR1 could serve as a potential biomarker for therapeutic strategies and highlight the need for further research to explore FGFR-targeted therapies in ccRCC."

Biomarker • Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • CD163 • FGFR1 • FGFR2 • FGFR3 • FGFR4 • GZMB • IFNG • PD-L1

The Prognostic Nutritional Index (PNI) as a Biomarker for Predicting Survival in Hepatocellular Carcinoma Patients Treated with Transarterial Chemoembolization and Lenvatinib, With or Without Programmed Death-1(PD-1) Inhibitors. (PubMed, Cardiovasc Intervent Radiol) - "The PNI score is a promising biomarker for predicting survival in HCC patients receiving TACE combined with lenvatinib, with or without PD-1 inhibitors. Low PNI is associated with poor survival outcomes, highlighting its potential utility in risk stratification and treatment planning."

Biomarker • IO biomarker • Journal • Cardiovascular • Hematological Disorders • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • Thrombosis • AFP

Outcomes by liver function in patients with unresectable hepatocellular carcinoma treated with nivolumab plus ipilimumab vs lenvatinib or sorafenib in the CheckMate 9DW trial (EASL 2025) - "NIVO + IPI showed a favorable benefit-risk profile vs LEN/SOR across ALBI subgroups. These results support NIVO + IPI as a potential 1L treatment option for pts with uHCC, regardless of liver function."

Clinical • Hepatocellular Cancer • Oncology • Solid Tumor

Nofazinlimab combined with lenvatinib versus placebo plus lenvatinib as first-line therapy for unresectable or metastatic hepatocellular carcinoma: A phase III, randomized, double-blind, multiregional study (CS1003-305) (ESMO 2025) - P3 | "Clinical meaningful improvements in PFS and ORR, alongside numerically competitive outcomes relative to current therapies, highlight the regimen's therapeutic value. Safety was manageable, with no new safety signals observed."

Clinical • Late-breaking abstract • Metastases • P3 data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology

Neoadjuvant toripalimab plus lenvatinib and GEMOX in resectable, high-risk intrahepatic cholangiocarcinoma: A randomized, multicenter, open-label phase II-III clinical trial (ESMO 2025) - P2/3 | "All pts received adjuvant capecitabine Q3W for 8 cycles after curative resection. During neoadjuvant therapy, all-grade treatment-related adverse events (TRAEs) occurred in 92% of pts (grade ≥3: 26.4%). Table: LBA11 Efficacy summary Neo arm (n=88) Ctrl arm (n=90) Median EFS, mo 18.0 8.7 HR 0.48 (95% CI 0.31-0.74; p=0.0006) Median OS, mo NR 31.4 HR 0.43 (95% CI 0.23-0.79; p=0.0050) Median RFS, mo 15.4 9.7 HR 0.69 (95% CI 0.45-1.06) ORR, n (%) 48 (54.5) - MPR, n (%) 17 (19.3) 0 pCR, n (%) 4 (4.5) 0 R0 resection rate, n (%) 84 (95.5) 84 (93.3) Conclusions For resectable high-risk iCCAs, neoadjuvant GOLP regimen demonstrated statistically significant improvement in EFS compared with traditional resection, with manageable safety."

Clinical • Late-breaking abstract • P2/3 data • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology

Efficacy and safety of toripalimab combined with Lenvatinib as first-line treatment for unresectable/advanced non–clear cell renal cell carcinoma: A prospective, single-arm, phase II trial (ESMO Asia 2025) - P=N/A | "The KEYNOTE-B61 study showed that pembrolizumab plus lenvatinib offers favorable efficacy and safety in advanced nccRCC, yet evidence for alternative first-line regimens remains limited. Toripalimab combined with lenvatinib showed promising antitumor activity and manageable toxicities as a first-line treatment for unresectable or advanced nccRCC."

Clinical • Metastases • P2 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Non Clear Cell Renal Cell Carcinoma • Oncology • Solid Tumor • TFE3

DLGAP5 regulates malignancy and lenvatinib sensitivity of hepatocellular carcinoma through AKT/mTOR/NF-κB pathway. (PubMed, Eur J Med Res) - "DLGAP5 promotes malignancy of HCC and reduces cell lenvatinib sensitivity by positively regulating the AKT/mTOR/NF-κB pathway, indicating that DLGAP5 functions as a potential biomarker for clinical prognosis and lenvatinib treatment in HCC."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor

Pucotenlimab Combined with Lenvatinib and eribulin in Patients with Advanced Sarcoma Failed in First-Line Therapy, a Single-Arm, Open-Label, Multicenter, Phase II Clinical Study (ChiCTR) - P2 | N=33 | Not yet recruiting | Sponsor: Shanghai Sixth People's Hospital; Shanghai Sixth People's Hospital

New P2 trial • Oncology • Sarcoma • Solid Tumor

Clinical Efficacy of Pucotenlimab Combined with Lenvatinib and SOX Versus SOX Alone in Patients with HER2-Negative Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: A Single-Center Randomized Controlled Trial (ChiCTR) - P=N/A | N=100 | Not yet recruiting | Sponsor: Department of Gastric Surgery, Fujian Medical University Union Hospital; Fujian Medical University Union Hospital

New trial • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • HER-2

FUGES032: Clinical Efficacy of Pucotenlimab Combined With Lenvatinib and SOX Versus SOX Alone in Patients With HER2-Negative Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (clinicaltrials.gov) - P1 | N=100 | Enrolling by invitation | Sponsor: Fujian Medical University

New P1 trial • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • HER-2

Pucotenlimab Combined with Lenvatinib and eribulin in Patients with Advanced Melanoma Failed in First-Line Therapy, a Single-Arm, Open-Label, Multicenter, Phase II Clinical Study (ChiCTR) - P=N/A | N=35 | Not yet recruiting | Sponsor: Shanghai Sixth People's Hospital; Shanghai Sixth People's Hospital

New trial • Melanoma • Oncology • Solid Tumor