A Phase 1, Open-Label, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of ADCT-502 in Patients With Advanced Solid Tumors With HER2 Expression

This study evaluated ADCT-502 in participants with Advanced Solid Tumors with HER2 Expression. Participants participated in a dose-escalation phase (Part 1) and were due to participate in the dose expansion phase (Part 2). In Part 2, patients were due to receive the dose level identified in Part 1, but the study was terminated prior to the beginning of Part 2.

Start Date18 May 2017

Sponsor / Collaborator

ADC Therapeutics SA

100 Clinical Results associated with ADCT-502

100 Translational Medicine associated with ADCT-502

100 Patents (Medical) associated with ADCT-502

Literatures (Medical) associated with ADCT-502

01 Mar 2022·Cancer Treatment ReviewsQ1 · MEDICINE

The evolving panorama of HER2-targeted treatments in metastatic urothelial cancer: A systematic review and future perspectives

Q1 · MEDICINE

Review

Author: Patelli, Giorgio ; Siena, Salvatore ; Tosi, Federica ; Spina, Francesco ; Ghezzi, Silvia ; Righetti, Elena ; Sartore-Bianchi, Andrea ; Stabile, Stefano ; Amatu, Alessio ; Zeppellini, Annalisa

PURPOSEHER2 alterations are potential candidates for targeted treatments in metastatic urothelial/bladder cancer (mUC). ERBB2 gene amplification and mutations are found in around 6% and 4% of mUC, respectively.METHODSThis is a systematic review of clinical trials evaluating HER2-targeting (amplification and mutations) in mUC. We assigned each study to one of the following strategies: HER2-targeting with single agents, anti-HER2 agents in combination with cytotoxic chemotherapy, dual HER2 blockade, HER2-targeted antibody-drug conjugates (ADCs), and other novel therapeutic approaches.RESULTS36 clinical trials (17 with results and 19 ongoing) were included. As for ERBB2 amplification, anti-HER2 single agents (5 studies) and combinations with chemotherapy (4 studies) failed to provide any benefit, whereas dual HER2 blockade through monoclonal antibodies proved active in one trial in pretreated patients. Two studies assessed single-agent targeting for ERBB2 mutations with negative results. Most promising data come from 2 studies with ADCs in ERBB2 amplified tumors (disitamab-vedotin and trastuzumab-duocarmazine), while 2 other studies with TDM-1 and ADCT-502 was discontinued due to toxicity. In this category, trastuzumab-deruxtecan and other ADCs are still under investigation for either ERBB2-amplified or mutated mUC. Novel approaches include ADCs with immunotherapy (1 study with results), CAR-T cells, and HER2-sensitising vaccines.CONCLUSIONSERBB2 amplification could become a novel target in mUC, although the magnitude of clinical benefit remains to be clarified. To this regard, novel ADCs are the most promising strategy. ERBB2 mutations are still at very early stage of clinical study.

01 Sep 2020·Molecular Cancer TherapeuticsQ2 · MEDICINE

The Role of Specific ATP-Binding Cassette Transporters in the Acquired Resistance to Pyrrolobenzodiazepine Dimer–Containing Antibody–Drug Conjugates

Q2 · MEDICINE

Article

Author: Corbett, Simon ; Huang, Shiran ; van Berkel, Patrick H. ; Zammarchi, Francesca ; Howard, Philip W. ; Hartley, John A.

AbstractAntibody–drug conjugates (ADC) containing pyrrolobenzodiazepine (PBD) dimers are being evaluated clinically in both hematologic and solid tumors. These include ADCT-301 (camidanlumab tesirine) and ADCT-402 (loncastuximab tesirine) in pivotal phase II trials that contain the payload tesirine, which releases the PBD dimer warhead SG3199. An important consideration in future clinical development is acquired resistance. The aim was to generate and characterize PBD acquired resistant cell lines in both hematologic and solid tumor settings. Human Karpas-299 (ALCL) and NCI-N87 (gastric cancer) cells were incubated with increasing IC50 doses of ADC (targeting CD25 and HER2, respectively) or SG3199 in a pulsed manner until stable acquired resistance was established. The level of resistance achieved was approximately 3,000-fold for ADCT-301 and 3-fold for SG3199 in Karpas-299, and 8-fold for ADCT-502 and 4-fold for SG3199 in NCI-N87. Cross-resistance between ADC and SG3199, and with an alternative PBD-containing ADC or PBD dimer was observed. The acquired resistant lines produced fewer DNA interstrand cross-links, indicating an upstream mechanism of resistance. Loss of antibody binding or internalization was not observed. A human drug transporter PCR Array revealed several genes upregulated in all the resistant cell lines, including ABCG2 and ABCC2, but not ABCB1(MDR1). These findings were confirmed by RT-PCR and Western blot, and inhibitors and siRNA knockdown of ABCG2 and ABCC2 recovered drug sensitivity. These data show that acquired resistance to PBD-ADCs and SG3199 can involve specific ATP-binding cassette drug transporters. This has clinical implications as potential biomarkers of resistance and for the rational design of drug combinations.

01 May 2019·Current Treatment Options in OncologyQ2 · MEDICINE

Antibody-Drug Conjugates in Breast Cancer: a Comprehensive Review

Q2 · MEDICINE

Review

Author: Aftimos, Philippe ; Pondé, Noam ; Piccart, Martine

OPINION STATEMENTAntibody-drug conjugates are an elegant approach to cancer treatment that couples the specificity of monoclonal antibodies to the cytotoxicity of classic chemotherapy agents, permitting, at least in theory, increased activity and reduced toxicity. In breast cancer, the early success of trastuzumab-emtansine (T-DM1) in the HER2-positive metastatic setting led to great hopes, later dashed by results in the early setting (KRISTINE trial) and in combination with pertuzumab (MARIANNE trial). Parallel to this, development of ADCs in breast cancer has suffered other setbacks, including the recent failure of other agents (MM-302) as well as the suspension of a few programs (XMT-1522, ADCT-502) with the overall effect of dampening the impetus of this concept and halting/delaying the progress of drugs associated with it, particularly when immunotherapy is at the center of so many efforts. Numerous antibody-drug conjugates remain, however, in development, and could prove successful. Critically, ADCs could permit the introduction of novel concepts such as the expansion of potent anti-HER2 therapy to HER2-low breast cancer, treatment beyond resistance to T-DM1, and synergy in combination with immune checkpoint blockade. In the early setting, the ATEMPT trial may show that T-DM1 reduces toxicity while maintaining good outcomes for lower risk HER2+ patients. ADCs based on bispecific antibodies are also in development. Finally, breakthroughs are occurring in the orphan triple-negative breast cancer subtype with agents targeting surface proteins. The recent results of Sacituzumab govitecan suggest substantial activity in heavily pre-treated patients and underscore the enduring relevance of antibody drug conjugates as a path towards better outcomes.

100 Deals associated with ADCT-502

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Bladder Cancer	Phase 2	US	ADC Therapeutics SA	18 May 2017
Bladder Cancer	Phase 2	BE	ADC Therapeutics SA	18 May 2017
Breast Cancer	Phase 2	BE	ADC Therapeutics SA	18 May 2017
Advanced Malignant Solid Neoplasm	Phase 1	US	ADC Therapeutics SA	18 May 2017
Advanced Malignant Solid Neoplasm	Phase 1	BE	ADC Therapeutics SA	18 May 2017
Breast Cancer	Phase 1	US	ADC Therapeutics SA	18 May 2017
Malignant neoplasm of gastro-oesophageal junction	Phase 1	BE	ADC Therapeutics SA	18 May 2017
Malignant neoplasm of gastro-oesophageal junction	Phase 1	US	ADC Therapeutics SA	18 May 2017
Non-Small Cell Lung Cancer	Phase 1	US	ADC Therapeutics SA	18 May 2017
Non-Small Cell Lung Cancer	Phase 1	BE	ADC Therapeutics SA	18 May 2017

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03125200 (CTgov)	Phase 1	Advanced Malignant Solid Neoplasm \| Breast Cancer \| Bladder Cancer \| Non-Small Cell Lung Cancer \| Malignant neoplasm of gastro-oesophageal junction	21	ADCT-502 (Part 1: Dose 30μg/kg)	qgaoanddmv(fzxepvoaad) = dzbxryntur meucjknnys (fhmqtezhyd, jgwzxshlnz - cnjwipcfoi) View more	-	28 Aug 2019
				ADCT-502 (Part 1: Dose 60μg/kg)	qgaoanddmv(fzxepvoaad) = xibgbshdlx meucjknnys (fhmqtezhyd, hjtdqgyjtf - nvvwjymnwi) View more

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

ADCT-502

Overview

Basic Info

Structure/Sequence

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation