mipasetamab uzoptirine (ADCT-601) / Overland ADCT BioPharma - LARVOL DELTA

ADCT-601-102: A Study of Mipasetamab Uzoptirine (ADCT-601) in Participants With Solid Tumors (clinicaltrials.gov) - P1 | N=128 | Terminated | Sponsor: ADC Therapeutics S.A. | N=260 ➔ 128 | Trial completion date: Aug 2027 ➔ Apr 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Aug 2026 ➔ Apr 2025; Sponsor decided to halt further development of ADCT-601

Enrollment change • Monotherapy • Trial completion date • Trial primary completion date • Trial termination • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AXL

Lineage-dependence of the neuroblastoma surfaceome defines tumor cell state-dependent and independent immunotherapeutic targets. (PubMed, Neuro Oncol) - "Immunotherapeutic strategies for neuroblastoma must address the potential of epigenetic downregulation of antigen density as a mechanism for immune evasion. We identified several RTKs as candidate MES-specific immunotherapeutic target proteins for the elimination of therapy-resistant cells. We hypothesize that the phenomena of immune escape will be less likely when targeting pan-neuroblastoma cell surface proteins such as B7-H3 and L1CAM, and/or dual targeting strategies that consider both the ADRN- and MES-cell states."

IO biomarker • Journal • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor • AXL • CD276 • L1CAM

ADCT-601-102: A Study of Mipasetamab Uzoptirine (ADCT-601) in Participants with Solid Tumors (clinicaltrials.gov) - P1 | N=260 | Active, not recruiting | Sponsor: ADC Therapeutics S.A. | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Monotherapy • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AXL

QUANTITATIVE SYSTEMS PHARMACOLOGY MODELING OF MIPASETAMAB UZOPTERINE INTEGRATES KNOWLEDGE AND DEFINES DOSING STRATEGY FOR PATIENTS WITH SARCOMA (CTOS 2024) - P1 | "Objective: AXL overexpression is linked to high metastatic potential and chemotherapy resistance, which induces poor overall survival in some solid tumors, notably sarcoma and non-small cell lung cancer.1-3 ADCT-601 (mipasetamab uzoptirine; Mipa) is an antibody-drug conjugate (ADC) comprising a humanized anti-AXL antibody conjugated to a potent chemotherapeutic agent, SG3199 (pyrrolobenzodiazepine dimer cytotoxin), via a cleavable linker.4 Mipa demonstrated antitumor activity in preclinical mouse xenograft models of sarcoma, adenoid cystic carcinoma, and pancreatic cancer and clinical activity in patients with solid tumor in phase 1 trials.4-6 The goal was to develop a model predicting the biodistribution and antitumor effect of Mipa for virtual patients with sarcoma following various dosing regimens. A novel physiologically based pharmacokinetics (PK) quantitative systems pharmacology (QSP) model was developed to describe the effect of Mipa on sarcoma... A novel..."

Clinical • Adenoid Cystic Carcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • AXL

ADC Therapeutics Reports Third Quarter and Year-to-Date 2024 Financial Results and Provides Operational Update (PRNewswire) - "Based on the available clinical data and capital requirements for continued development, the Company will discontinue the Phase 1b ADCT-601 program targeting AXL as a single agent and/or in combination for patients with sarcoma, pancreatic cancer and non-small cell lung cancer...Progress continues in the Investigational New Drug (IND) enabling studies for the Company's exatecan-based programs for ADCs targeting Claudin-6, PSMA and NaPi2b, while our ASCT2 targeting ADC is in the drug candidate selection stage. The Company has selected one target to move toward IND which is expected to be disclosed in 2025."

Discontinued • Pipeline update • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Sarcoma • Solid Tumor

Lineage-dependence of the neuroblastoma surfaceome defines tumor cell state-dependent and independent immunotherapeutic targets. (PubMed, bioRxiv) - "We identified several receptor tyrosine kinases (RTKs) enriched in MES-dominant samples and showed that AXL targeting with ADCT-601 was potently cytotoxic in MES-dominant cell lines and showed specific anti-tumor activity in a MES cell line-derived xenograft...Several plasma membrane proteins are being developed as immunotherapeutic targets in this disease. Here we define which cell surface proteins are susceptible to epigenetically regulated downregulation during an adrenergic to mesenchymal cell state switch and propose immunotherapeutic strategies to anticipate and circumvent acquired immunotherapeutic resistance."

IO biomarker • Journal • Tumor cell • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor • AXL • CD276 • L1CAM

ADC Therapeutics Reports First Quarter 2024 Financial Results and Provides Business Updates (GlobeNewswire) - "ADCT-601 (targeting AXL): Additional data updates from the Phase 1 study in patients with sarcoma, pancreatic cancer and NSCLC in 2H 2024. ADCT-602 (targeting CD22): Additional data from the Phase 1 study in 2H 2024....Net product revenues were $17.8 million for the first quarter 2024, compared to $19.0 million for the first quarter 2023. Net product revenues are for U.S. sales of ZYNLONTA."

P1 data • Sales • B Acute Lymphoblastic Leukemia • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Sarcoma • Solid Tumor

Preclinical anti-tumorigenic evaluation of AXL targeting antibody-drug-conjugate in an adenoid cystic carcinoma cell line xenograft model (AACR 2024) - "Strikingly, by day 6 post-treatment, tumor volume began to shrink and eventually resulted in CR except in all but one case. These results demonstrate ADCT-601 is an effective drug with significant anti-tumor activity in our preclinical models and is worthy of additional investigation to determine its translational potential."

Late-breaking abstract • Preclinical • Adenoid Cystic Carcinoma • Oncology • Salivary Gland Cancer • AXL

Phase 1b trial Mipasetamab Uzoptirine (ADCT-601-102) dose escalation in patients with advanced bone and soft tissue sarcomas (AACR 2024) - P1 | "Background: AXL is a cell surface receptor tyrosine kinase widely expressed in solid tumors (ST), including sarcomas. The MTD was not established. Due to the incidence of TEAE judged related to Mipa and the preliminary activity observed, 15mg was selected as the highest dose to be tested in a fixed dose Q3W regimen. The study continues to enroll to further optimize Mipa dosing regimen and in dose escalation with gemcitabine."

Clinical • Metastases • P1 data • Adenoid Cystic Carcinoma • Gastrointestinal Cancer • Oncology • Osteosarcoma • Pancreatic Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • AXL

ADCT-601-102: A Study of Mipasetamab Uzoptirine (ADCT-601) in Participants With Solid Tumors (clinicaltrials.gov) - P1 | N=260 | Recruiting | Sponsor: ADC Therapeutics S.A. | N=196 ➔ 260

Combination therapy • Enrollment change • Metastases • Monotherapy • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AXL

ADC Therapeutics Announces Abstracts Accepted for Presentation at the American Association for Cancer Research (AACR) Annual Meeting (GlobeNewswire) - "ADC Therapeutics SA...today announced abstracts on its novel antibody drug conjugates (ADCs) have been accepted for presentation at the American Association for Cancer Research (AACR) Annual Meeting, which will be held in San Diego, CA from April 5-10, 2024....'We’re excited to share compelling preclinical data supporting the future clinical development of the next-generation ADCs in our solid tumor portfolio, including those targeting Claudin-6 and NaPi2b, at the AACR Annual Meeting'...'We’re also looking forward to research from independent studies that highlight the potential of another investigational ADC, ADCT-601 targeting AXL.'"

Clinical data • P1 data • Preclinical • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology • Soft Tissue Sarcoma • Solid Tumor

ADC Therapeutics Reports Fourth Quarter and Full Year 2023 Financial Results and Provides Business Updates (GlobeNewswire) - "ADCT-602 (targeting CD22): Dose escalation and expansion in the Phase 1 study with relapsed or refractory acute lymphoblastic leukemia in collaboration with MD Anderson Cancer Center is progressing and additional clinical trial sites are being added to accelerate enrollment....ADCT-601 (targeting AXL): Additional data updates from the Phase 1 study in patients with sarcoma, pancreatic cancer and NSCLC in 2024. ADCT-602 (targeting CD22): Additional data from the Phase 1 study in 2024."

P1 data • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Sarcoma • Solid Tumor

ADC Therapeutics Provides Business Updates (GlobeNewswire) - P1b | N=196| NCT05389462 | Sponsor: ADC Therapeutics S.A.| "ADC Therapeutics SA...today provided business updates...ADCT-601 (targeting AXL): In the Phase 1b trial, the maximum-tolerated dose has been reached, and the study is currently in dose optimization. There have been early signs of antitumor activity in both monotherapy and in combination. The dose-optimization/ expansion phase is comprised of a monotherapy arm including patients with sarcoma, pancreatic cancer and AXL-expressing non-small cell lung cancer (NSCLC) and a combination arm with gemcitabine in patients with sarcoma and pancreatic cancer....Additional data updates from the Phase 1 study in patients with sarcoma, pancreatic cancer and NSCLC in 2024."

P1 data • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Sarcoma • Solid Tumor

ADCT-601-102: A Study of Mipasetamab Uzoptirine (ADCT-601) in Participants With Solid Tumors (clinicaltrials.gov) - P1 | N=196 | Recruiting | Sponsor: ADC Therapeutics S.A. | Phase classification: P1b ➔ P1

Phase classification • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AXL

ADC Therapeutics Reports Third Quarter 2023 Financial Results and Provides Business Updates (GlobeNewswire) - "ADCT-601 (targeting AXL): Initial data from Phase 1 study in 1H 2024; ADCT-901 (targeting KAAG1): Initial data from Phase 1 study in 1H 2024; ADCT-602 (targeting CD22): Additional data from Phase 1 study in 1H 2024."

P1 data • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Oncology • Solid Tumor

PRE-CLINICAL ACTIVITY OF ADCT-601, AN ANTIBODY-DRUG CONJUGATE TARGETING AXL IN SOFT-TISSUE SARCOMA (CTOS 2023) - No abstract available

Preclinical • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • AXL

ADCT-601-102: A Study of Mipasetamab Uzoptirine (ADCT-601) in Participants With Solid Tumors (clinicaltrials.gov) - P1b | N=196 | Recruiting | Sponsor: ADC Therapeutics S.A. | N=66 ➔ 196

Combination therapy • Enrollment change • Metastases • Monotherapy • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AXL

TRIAL IN PROGRESS: A PHASE 1B DOSE-ESCALATION STUDY OF ADCT-601 AS MONOTHERAPY OR WITH GEMCITABINE IN PATIENTS WITH SELECT ADVANCED SOLID TUMORS (CTOS 2023) - No abstract available

Clinical • Metastases • Monotherapy • P1 data • Oncology • Solid Tumor

ADC Therapeutics Reports Second Quarter 2023 Financial Results and Provides Business Updates (GlobeNewswire) - "ADCT-901 (targeting KAAG1): Initial data from Phase 1 study in 1H 2024. ADCT-601 (targeting AXL): Initial data from Phase 1 study in 1H 2024. ADCT-602 (targeting CD22): Additional data from Phase 1 study in 1H 2024....R&D expenses were $31.9 million for the quarter ended June 30, 2023, compared to $48.5 million for the same quarter in 2022. R&D expenses decreased due to less investment in Cami (camidanlumab tesirine) due to the completion of the Phase 2 study in 2022 and the Company’s decision to seek a partner to progress the program, as well as less investment in other development programs."

Commercial • P1 data • Oncology • Solid Tumor

ADC Therapeutics Reports Fourth Quarter and Full Year 2022 Financial Results and Provides Business Updates (Businesswire) - "Upcoming Expected Milestones: ZYNLONTA...Complete enrollment of the LOTIS-5 study in 2024; Preliminary safety and efficacy data from the LOTIS-9 study in 2024; Preliminary safety and efficacy data from the LOTIS-7 study in 2024....ADCT-901 (targeting KAAG1): Preliminary data from Phase 1 dose escalation study in 1H 2024. ADCT-601 (targeting AXL): Preliminary data from Phase 1 dose escalation/expansion study in 1H 2024."

P1 data • P2 data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Generation of DAR1 Antibody-Drug Conjugates for Ultrapotent Payloads Using Tailored GlycoConnect Technology. (PubMed, Bioconjug Chem) - "GlycoConnect technology can be readily adapted to provide different drug-to-antibody ratios (DARs) and is currently also evaluated in various clinical programs, including ADCT-601 (DAR2), MRG004a (DAR4), and XMT-1660 (DAR6). In a follow-up experiment, HCC-1954 tumor spheroids were treated with either an AlexaFluor647-labeled DAR1 or DAR2 PBD-based ADC to study the effect on tumor penetration. Significant improvement of tumor spheroid penetration was observed for the DAR1 ADC compared to the DAR2 ADC at an equal payload dose, underlining the potential of a lower DAR for ADCs bearing ultrapotent payloads."

Journal • Oncology

Progressing an ADC Through Preclinical Development Into the Clinic: ADCT-601 Case Study (ADC London 2023) - "• Outlining the preclinical development of ADCT-601, a novel Pyrrolobenzodiazepine Dimer-based antibody–drug conjugate targeting AXL-expressing cancers • Exploring combinations with other approved agents • Bringing ADCT-601 to the clinic"

Preclinical • Oncology • AXL

Preclinical data demonstrates SonoTran increased efficacy of ADCT-601 in human renal cancer model (OxSonics Press Release) - "The data presented in the poster was a collaboration between OxSonics Therapeutics and ADCT to assess the ability of SonoTran^® to enhance the efficacy of ADCT-601 in a human xenograft model of renal cancer....The study evaluated two doses of ADCT-601, one known to be efficacious (1mg/kg) when administered alone and one that is ineffective alone (0.3mg/kg). During the study, the lower dose was administered with and without SonoTran^®. The results showed the mice treated with 0.3mg/kg ADCT-601 + SonoTran^® had significant tumor growth delay, which led to a significant improvement in survival compared to the control groups. The efficacy of the 0.3mg/kg ADCT-601 + SonoTran^® was equivalent to that seen with 1mg/kg ADCT-601, indicating that the SonoTran^® combination enhanced potency by 3.3 times."

Preclinical • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma

Ultrasound-induced cavitation enhances therapeutic efficacy of AXL-targeting ADC leading to improved survival in a human xenograft model of renal cancer. (AACR-NCI-EORTC 2022) - "The purpose of this study was to test a suboptimal single dose of mipasetamab uzoptirine (ADCT-601), an ADC targeting the AXL protein, in combination with ultrasound-induced cavitation in a preclinical mouse model of renal cancer...This was demonstrated for a suboptimal ADC dose, indicating that ultrasound-mediated drug delivery could be used to reduce the administered dose while preserving therapeutic efficacy. These preclinical data warrant further evaluation of this promising combination in the clinic."

Preclinical • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • AXL

ADC Therapeutics Doses First Patient in Phase 1b Clinical Trial of ADCT-601 Targeting AXL as a Single Agent and in Combination with Gemcitabine in Advanced Solid Tumors (GlobeNewswire) - "ADC Therapeutics SA...announced the first patient has been dosed in the Phase 1b clinical trial evaluating ADCT-601 (mipasetamab uzoptirine) targeting AXL as a single agent and in combination with gemcitabine in patients with selected advanced solid tumors....he first arm of the trial will enroll approximately 18 patients with sarcoma, a tumor resistant to current available cancer treatments in which AXL is overexpressed."

Trial status • Oncology • Solid Tumor