olaviztabart cilotecan (LY4101174) / Eli Lilly - LARVOL DELTA

A phase 1 study of LY4101174 (ETx-22), an antibody-drug conjugate targeting nectin-4, in patients with advanced or metastatic urothelial cancer and other solid tumors (trial in progress) (AACR 2024) - "Background: Nectin-4 is a cell adhesion molecule expressed in multiple tumor types.1 Enfortumab vedotin (EV), an antibody-drug conjugate (ADC) comprising a fully humanized nectin-4 antibody conjugated to the microtubule inhibitor, monomethyl auristatin E (MMAE), is approved for the treatment of advanced urothelial cancer (UC). 2016 Cancer Res 76(10):3003-13.2Azim H et al. 2023 Mol Cancer Ther 22(12_Suppl):B128."

ADC • Clinical • First-in-human • Metastases • P1 data • Breast Cancer • Esophageal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer

Initial results from EXCEED, a phase 1 study of LY4101174, 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: NCT06238479 Background: Enfortumab vedotin plus pembrolizumab (EVP) is the current first-line standard of care for locally advanced / metastatic urothelial carcinoma (mUC). LY4101174 has demonstrated clinical activity at Q3W dose levels, including in EV pre-treated mUC, suggesting Nectin-4 remains an important therapeutic target. Dose and duration on treatment were mainly limited by grade ≥3 hematologic toxicity requiring the use of prophylactic G-CSF."

ADC • Metastases • P1 data • Febrile Neutropenia • Hematological Disorders • Leukopenia • Neutropenia • Oncology • Solid Tumor • Thrombocytopenia • Urothelial Cancer • NECTIN4

ASCO 2026: Initial Results from EXCEED, a Phase 1 Study of LY4101174, an Antibody-Drug Conjugate Targeting Nectin-4, in Participants with Advanced or Metastatic Urothelial Carcinoma (UroToday) - "Overall, 92% of metastatic urothelial carcinoma participants had received prior enfortumab vedotin, with 19% discontinuing enfortumab vedotin due to treatment-related toxicity...LY4101174 exhibited a mostly linear, dose-proportional pharmacokinetics up to 4.0 mg/kg, and up to 3.2 mg for exatecan...Enfortumab vedotin-associated adverse events (ie, skin toxicities, peripheral neuropathy, ocular toxicity, and hyperglycemia) were minimal...In the 76 efficacy evaluable metastatic urothelial carcinoma participants treated with 2.4-4.0 mg/kg every 3 weeks (93% enfortumab vedotin-pretreated), the objective response rate was 20%, and the disease control rate was 72%, with 14 partial responses (18%) and 40 stable disease (53%). While the 4 mg/kg dose demonstrated promising antitumor activity (objective response rate 36%)."

P1 data • Urothelial Cancer

LOXO-ENC-23001: A Study of LY4101174 in Participants With Recurrent, Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=490 | Active, not recruiting | Sponsor: Eli Lilly and Company | Recruiting ➔ Active, not recruiting

Enrollment closed • Breast Cancer • Esophageal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

LY4101174: Primary completion and completion of P1 EXCEED trial (NCT06238479) for metastatic solid tumors in Mar 2027 (Eli Lilly) - Q3 2025 Results

Trial completion date • Trial primary completion date • Oncology • Solid Tumor

A Study of LY4101174 in Participants With Recurrent, Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=490 | Recruiting | Sponsor: Eli Lilly and Company | Trial primary completion date: Aug 2026 ➔ Mar 2027

Trial primary completion date • 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

A Study of LY4101174 in Participants With Recurrent, Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=490 | Recruiting | Sponsor: Eli Lilly and Company | N=280 ➔ 490

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

LY4101174: Primary completion of P1 trial (NCT06238479) in participants with recurrent, advanced or metastatic solid tumors in Aug 2026 (Eli Lilly) - Q3 2024 Results: Completion of P1 trial in participants with recurrent, advanced or metastatic solid tumors in Mar 2027

Trial completion date • Trial primary completion date • Oncology • Solid Tumor

LY4101174: Primary completion of P1 NECTIN-4 ADC 1 trial (NCT06238479) for advanced or metastatic solid tumors in Aug 2026 (Eli Lilly, Eli Lilly) - Q3 2024 Results: Completion of P1 NECTIN-4 ADC 1 trial for advanced or metastatic solid tumors in Mar 2027

Trial completion date • Trial completion date • Trial primary completion date • Trial primary completion date • Oncology • Solid Tumor

LY4101174: Primary completion of P1 NECTIN-4 ADC 1 trial (NCT06238479) for advanced or metastatic solid tumors in Aug 2026 (Eli Lilly, Eli Lilly) - Q3 2024 Results: Completion of P1 NECTIN-4 ADC 1 trial for advanced or metastatic solid tumors in Mar 2027

Trial completion date • Trial completion date • Trial primary completion date • Trial primary completion date • Oncology • Solid Tumor

ETx-22: a novel nectin-4-directed antibody drug conjugate, demonstrates safety and potent antitumor activity in low nectin-4 expressing tumors. (PubMed, Cancer Res Commun) - "ETx-22 has a highest non severely toxic dose of over 20 mg/kg in non-human primates without signs of important skin toxicity. ETx-22 represents a valuable therapy, for the treatment of patients with nectin-4 expressing tumors including those that have become resistant to enfortumab vedotin treatment."

Journal • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • NECTIN4

A Study of LY4101174 in Participants With Recurrent, Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=280 | 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

A Study of LY4101174 in Participants With Recurrent, Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=280 | Not yet recruiting | Sponsor: Eli Lilly and Company

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

Loxo@Lilly Unveils Three New Oncology Programs at 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (PRNewswire) - "[email protected] that preclinical data for agents targeting KRAS G12D, multiple oncogenic KRAS mutations and Nectin-4, will be presented at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics...These programs are among the next slate of new oncology agents planned to enter clinical trials for Loxo@Lilly in 2024. The poster presentations will include preclinical characterization data for a highly potent inhibitor of KRAS G12D that is selective against wild-type KRAS, a highly potent and isoform-selective pan-KRAS inhibitor with activity against a broad spectrum of the most common activating KRAS mutations and high selectivity over wild-type HRAS and NRAS, and a fully human monoclonal anti-Nectin-4 antibody conjugated to a topoisomerase I (TOPO 1) inhibitor."

New trial • Preclinical • Oncology

Eli Lilly completes acquisition of Nectin-4 ADC developer for nearly US$500 million (Sohu.com) - "...foreign media reported that Eli Lilly completed the acquisition of Nectin-4 ADC developer Emergence on August 24. Emergence’s official website also shows it as a wholly-owned subsidiary of Eli Lilly...According to foreign media reports, Eli Lilly paid approximately US$470 million to acquire Emergence, including US$335 million in potential milestones....Emergence Therapeutics is a company focused on the development of ADC drugs. Its core pipeline is a Nectin-4 ADC drug (ETx-22)."

M&A • Bladder Cancer • Breast Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer

Preclinical characterization of ETx-22, a next-generation antibody drug conjugate (ADC) targeting nectin-4. (AACR-NCI-EORTC 2023) - No abstract available

Preclinical • Oncology

"ETx-22https://www.adcreview.com/drugmap/etx-22-is-an-next-gen-anti-nectin-4-adc/" (,@OncoZine)

Review • NECTIN4

Emergence Therapeutics raises €87 million Series A financing to advance Nectin-4 ADC (GlobeNewswire) - "Emergence Therapeutics AG...announces that it has closed an €87 million series A financing round...Proceeds from this funding round will be used to advance the company’s next-generation antibody drug conjugate (ADC) targeting Nectin-4 to clinical proof-of-concept as well as the development of additional ADC programs...ETx-22 will initially be developed for bladder and triple negative breast cancer as well as malignancies with medium and low nectin-4 expression levels, including ovarian, head and neck and lung cancer."

Financing • Biliary Tract Cancer • Bladder Cancer • Breast Cancer • Cholangiocarcinoma • Gynecologic Cancers • Head and Neck Cancer • Lung Cancer • Oncology • Ovarian Cancer • Triple Negative Breast Cancer