Database for
Therapeutic Antibodies
Therapeutic Antibodies
| Entry ID | 10 |
| INN | Loncastuximab tesirine |
| Status | Approved |
| Drug code(s) | ADCT-402 |
| Brand name | Zynlonta |
| mAb sequence source | mAb humanized |
| General Molecular Category | ADC |
| Format, general category | Full length Ab conjugate |
| Format details | None |
| Isotype (Fc) | IgG1 |
| Light chain isotype | kappa |
| Linker | Valine-alanine, Cleavable linker |
| Ave. DAR | 2.3 |
| Conjugated/fused moiety | DNA binding, Pyrrolobenzodiazepine (PBD) dimer SG3199 |
| Discovery method/technology | None |
| Target(s) | CD19 |
| Indications of clinical studies | Non-Hodgkin lymphoma, B-ALL |
| Primary therapeutic area | Cancer |
| Most advanced stage of development (global) | Approved EU, US |
| Status | Active |
| Start of clinical phase (IND filing or first Phase 1) | February 01, 2016 |
| Start of Phase 2 | |
| Start of Phase 3 | August 01, 2018 |
| Date BLA/NDA submitted to FDA | September 21, 2020 |
| Year of first approval (global) | 2021 |
| Date of first US approval | April 23, 2021 |
| INN, US product name | Loncastuximab tesirine, loncastuximab tesirine-lpyl |
| US or EU approved indications | Treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low grade lymphoma, and high-grade B-cell lymphoma. |
| Company | ADC Therapeutics Sarl |
| Licensee/Partner | SOBI (Swedish Orpha Biovitrum) |
| Comments about company or candidate | Dec 20, 2022: Approved in EU FDA approved on April 23, 2021. This indication (B-cell lymphoma) is approved under accelerated approval based on overall response rate. The BLA submission was supported by data from the open-label, single-arm Phase 2 LOTIS 2 study (NCT03589469). This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.This application was granted priority review and orphan drug designation. Dec 2020: ADC Therapeutics SA and Overland Pharmaceuticals, a fully integrated biopharmaceutical company backed by Hillhouse Capital, today announced that they have jointly formed a new company, Overland ADCT BioPharma (CY) Limited, to develop and commercialize four of ADC Therapeutics’ antibody drug conjugate (ADC) product candidates for difficult-to-treat hematologic and solid tumors – loncastuximab tesirine (Lonca), ADCT-601, ADCT-602 and ADCT-901 – in greater China and Singapore. ADCT submitted the Initial BLA and a request for priority review designation on 21 Sep 2020. The Chemistry, Manufacturing, and Controls (CMC) information for the BLA was submitted as a presubmission on Aug 7, 2020. July 17, 2020: ADC Therapeutics SA announced that the first patient has been dosed in the pivotal Phase 2 portion of LOTIS 3, a Phase 1/2 clinical trial evaluating loncastuximab tesirine (Lonca, formerly ADCT-402) in combination with ibrutinib in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) or mantle cell lymphoma (MCL). “Based on the encouraging interim data Lonca and ibrutinib demonstrated in Phase 1, the trial was amended to a Phase 1/2 protocol intended to support the submission of a supplemental Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA),” said Jay Feingold, MD, PhD, Senior Vice President and Chief Medical Officer of ADC Therapeutics. “We are pleased to have dosed the first patient in the pivotal Phase 2 portion of this trial as we continue advancing Lonca as both a single agent and in combination with other therapies for patients with non-Hodgkin lymphoma. We are on track to file a BLA with the FDA for Lonca as monotherapy for the treatment of relapsed or refractory DLBCL in the second half of 2020.” June 2020: Company is on track to file a Biologics License Application (BLA) with the U.S. Food and Drug Administration for Lonca for the treatment of relapsed or refractory DLBCL in the second half of 2020 NCT04384484 Phase 3 in diffuse large B cell lymphoma not yet recruiting when posted on May 12, 2020. NCT03589469 Phase 2 LOTIS 2 study started in Aug 2018. NCT03685344 Phase 1 study in Diffuse Large B-Cell, Mantle Cell, or Follicular Lymphoma recruiting as of Dec 6, 2018. Aug 7, 2018: ADC Therapeutics, an oncology drug discovery and development company that specializes in the development of proprietary antibody drug conjugates (ADCs), today announced that the first patient has been dosed in its Phase II clinical trial intended to support the submission of Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA). The clinical trial is evaluating the efficacy and safety of ADCT-402 (loncastuximab tesirine) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). June 9, 2017: U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to ADCT-402 for the treatment of diffuse large B-cell lymphoma and mantle cell lymphoma. June 2017: In a presentation at the 14th International Conference on Malignant Lymphoma, interim results from the Phase I, open label, dose-escalating study of ADCT-402 evaluating tolerability, safety, pharmacokinetics and efficacy in patients with relapsed or refractory non-Hodgkin’s lymphoma (r/r NHL) were reported. Data were presented from 62 evaluable patients with a median age of 67 years and a median of 3 previous therapies (range 1-10). NCT02669017 and NCT02669264 Phase 1 studies recruiting as of March 2017 NCT02669264 Phase 1 in ALL started in March 2016 terminated (The study was early terminated prior to part 2 because of slow accrual.) |
| Full address of company | Biopôle, Route de la Corniche 3B, 1066 Epalinges, Switzerland Europe Switzerland https://www.adctherapeutics.com/contact/ |
ADCT-402 is an antibody drug conjugate (ADC) composed of a humanized antibody directed against human cluster of differentiation 19 (CD19), stochastically conjugated via a valine-alanine cleavable, maleimide linker to a pyrrolobenzodiazepine (PBD) dimer cytotoxin. Described as chimeric in WHO Proposed INN list 117.
| Anticipated events | None |
| Factor(s) contributing to discontinuation | None |