LY4052031 / Eli Lilly - LARVOL DELTA

Initial results from NEXUS-01, a phase 1 study of LY4052031, an antibody-drug conjugate targeting Nectin-4, in participants with advanced or metastatic urothelial carcinoma. (ASCO 2026) - P1 | "Funded by Eli Lilly and Company Clinical Trial Registration Number: NCT06465069 Background: Enfortumab vedotin plus pembrolizumab (EVP) is the current first-line standard of care for locally advanced / metastatic urothelial carcinoma (mUC). LY4052031 demonstrated promising clinical activity at multiple dose levels, including in EV pre-treated mUC. CYP2D6 AS specific dose optimization is ongoing and updated results will be presented."

ADC • Metastases • P1 data • Alopecia • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Immunology • Mucositis • Oncology • Solid Tumor • Urothelial Cancer • NECTIN4

ASCO 2026: Initial Results from NEXUS-01, a Phase 1 Study of LY4052031, an ADC Targeting Nectin-4, in Participants with Advanced or Metastatic Urothelial Carcinoma (UroToday) - "Among 48 efficacy-evaluable patients, the overall response rate (ORR) was 42% (20/48), including confirmed complete responses in 4% and partial responses in 38%. The disease control rate (DCR) was 79% (38/48). Responses were observed regardless of prior enfortumab vedotin exposure. Among patients previously treated with EV (n=36), ORR was 33% (12/36), and DCR was 75% (27/36). In EV-naïve patients (n=12), ORR reached 67% (8/12) with a DCR of 92% (11/12)....Among EV-pretreated, topoisomerase-I ADC–naïve patients with CYP2D6 activity scores ≥0.5, the median duration of response was 7.4 months (95% CI: 2.7–not estimable) among nine confirmed responders."

P1 data • Urothelial Cancer

Lilly Presentation Highlights:…LY4052031 (investigational ADC targeting Nectin-4) (PRNewswire) - "In an oral presentation, initial results will be shared from the Phase 1 NEXUS-01 study evaluating LY4052031, an ADC targeting Nectin-4, in patients with advanced or metastatic urothelial carcinoma."

P1 data • Urothelial Cancer

A next generation treatment for Nectin-4 positive cancers - Preclinical characterization of LY4052031, an anti-Nectin-4 antibody, conjugated to a novel camptothecin payload (AACR 2024) - "The approval of enfortumab vedotin-ejfv, an anti-Nectin-4 based antibody-drug conjugate (ADC) with a microtubule inhibitor payload, either as a single agent or in combination with pembrolizumab has been a significant advancement in the treatment of metastatic urothelial cancer. Overall, LY4052031 exhibits specificity, selectivity, potency, and effectiveness as a next generation therapy to treat Nectin-4 positive tumors. An IND submission is planned for 2024."

Preclinical • Bladder Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Urothelial Cancer • TOP1

NEXUS-01: A Study of LY4052031 in Participants With Advanced or Metastatic Urothelial Cancer or Other Solid Tumors (clinicaltrials.gov) - P1 | N=420 | Recruiting | Sponsor: Eli Lilly and Company | Suspended ➔ Recruiting

Enrollment open • Bladder Cancer • Breast Cancer • Cervical Cancer • Esophageal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer

NEXUS-01: A Study of LY4052031 in Participants With Advanced or Metastatic Urothelial Cancer or Other Solid Tumors (clinicaltrials.gov) - P1 | N=420 | Suspended | Sponsor: Eli Lilly and Company | Recruiting ➔ Suspended

Trial suspension • Bladder Cancer • Breast Cancer • Cervical Cancer • Esophageal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer

NEXUS-01, a phase 1 study of LY4052031, an antibody-drug conjugate targeting Nectin-4 in participants with advanced or metastatic urothelial carcinoma or other solid tumors. (ASCO-GU 2025) - P1 | "Enfortumab vedotin (EV) is a first generation anti-nectin-4 antibody-drug conjugate (ADC) comprising a fully humanized antibody conjugated to an MMAE payload with heterogeneous DAR 4 and is approved in metastatic urothelial carcinoma (mUC) both as a single agent in treatment refractory disease and as first-line treatment in combination with pembrolizumab. Key secondary objectives are to evaluate the pharmacokinetic profile, immunogenicity, and antitumor activity of LY4052031 per RECIST v1.1. Nectin-4 expression and other biomarker data will be generated and correlated with clinical activity."

Metastases • P1 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Urothelial Cancer • TOP1

NEXUS-01: A Study of LY4052031 in Participants With Advanced or Metastatic Urothelial Cancer or Other Solid Tumors (clinicaltrials.gov) - P1 | N=420 | Recruiting | Sponsor: Eli Lilly and Company | N=220 ➔ 420

Enrollment change • Bladder Cancer • Breast Cancer • Cervical Cancer • Esophageal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer

NEXUS-01, a phase 1 study of LY4052031, an antibody-drug conjugate targeting Nectin-4 in participants with advanced or metastatic urothelial carcinoma or other solid tumors (Trial in Progress) (EORTC-NCI-AACR 2024) - P1 | "Enfortumab vedotin (EV) is a first generation anti-nectin-4 antibody-drug conjugate (ADC) comprising a fully humanized antibody conjugated to an MMAE payload with heterogeneous DAR 4 and is approved in metastatic urothelial carcinoma (mUC) both as a single agent in treatment refractory disease and as first-line treatment in combination with pembrolizumab. Key secondary objectives are to evaluate the pharmacokinetic profile, immunogenicity, and antitumor activity of LY4052031 per RECIST v1.1. Nectin-4 expression and other biomarker data will be generated and correlated with clinical activity."

Metastases • P1 data • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer • TOP1

NEXUS-01: A Study of LY4052031 in Participants With Advanced or Metastatic Urothelial Cancer or Other Solid Tumors (clinicaltrials.gov) - P1 | N=220 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Bladder Cancer • Breast Cancer • Cervical Cancer • Esophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer

NEXUS-01: A Study of LY4052031 in Participants With Advanced or Metastatic Urothelial Cancer or Other Solid Tumors (clinicaltrials.gov) - P1 | N=220 | Not yet recruiting | Sponsor: Eli Lilly and Company

Metastases • New P1 trial • Bladder Cancer • Breast Cancer • Cervical Cancer • Esophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer

Lilly Announces Details of Presentations at 2024 American Association for Cancer Research (AACR) Annual Meeting (PRNewswire) - "Eli Lilly and Company...announced that preclinical data for agents targeting Nectin-4, KRAS G12D, and BRM (SMARCA2) will be presented at the American Association for Cancer Research (AACR) Annual Meeting....The presentations will include new preclinical data for a fully human monoclonal anti-Nectin-4 antibody conjugated to a novel topoisomerase I inhibitor and a highly potent and orally administered inhibitor of KRAS G12D that is selective against wild-type KRAS. In addition, preclinical data on a potent and selective BRM (SMARCA2) inhibitor for the treatment of BRG1 (SMARCA4) mutated cancers will be presented in collaboration with Foghorn Therapeutics. Investigational New Drug (INDs) applications are planned for all three programs in 2024."

IND • Preclinical • Solid Tumor