Abstract 4085
Background
AXL, a member of the TAM family of receptor tyrosine kinases, is overexpressed in various cancers and overexpression is linked to metastasis, poor survival, and drug resistance. ADCT-601, an AXL-targeted antibody-drug conjugate, has shown potent and durable antitumor activity in preclinical human cancer models via AXL-mediated delivery of a pyrrolobenzodiazepine dimer warhead. Here we report interim data from a phase 1 clinical trial of ADCT-601 (NCT03700294; ADC Therapeutics) in patients (pt) with selected advanced solid tumors.
Methods
This phase 1 dose-escalation and dose-expansion study is currently enrolling pts aged ≥18 years with relapsed or refractory tumors. The primary objective is to characterize the safety and tolerability of ADCT-601 and to identify the recommended dose for future studies. Pts receive intravenous infusions of ADCT-601 once every 3 weeks starting at 50 µg/kg, with subsequent cohorts enrolled at escalating doses according to a standard 3 + 3 design.
Results
As of data cutoff (April 12, 2019), 8 pts were treated at doses of 50–100 µg/kg. The median (range) age was 70 (46–77) years. Pathological subtypes enrolled are colorectal cancer (4 pts) and chondrosarcoma, head and neck carcinoma, ovarian carcinoma, and esophageal carcinoma (1 pt each). Six pts had received ≥4 previous lines of therapy. One pt treated at 100 µg/kg had a dose-limiting toxicity of grade 3 hematuria, which resulted in hospitalization and was possibly related to ADCT-601. The most common treatment-emergent adverse events, regardless of relationship to ADCT-601, were abdominal pain, erythema, fatigue, peripheral edema, and maculopapular rash (each occurring in 2 pts). The following 4 pts had undergone disease assessment at data cutoff: 1 pt (chondrosarcoma) had a partial response, 1 pt (head and neck carcinoma) had stable disease, and 2 pts (ovarian carcinoma and esophageal carcinoma) had progressive disease.
Conclusions
This study is continuing to enroll pts and will identify the recommended dose of ADCT-601. Updated results, including pharmacokinetic data, will be presented at the meeting.
Clinical trial identification
NIH (https://clinicaltrials.gov/ct2/show/NCT03700294) October 9, 2018.
Editorial acknowledgement
Editorial support was provided by Sindhu Doppalapudi and Becky Salisbury at Fishawack Communications Ltd, funded by ADC Therapeutics Ltd.
Legal entity responsible for the study
ADC Therapeutics.
Funding
ADC Therapeutics.
Disclosure
A.W. Tolcher: Advisory / Consultancy, Research grant / Funding (institution): AbbVie; Advisory / Consultancy, Research grant / Funding (institution): ADC Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): Adagene; Advisory / Consultancy: Agenus; Advisory / Consultancy: AroBioTX; Advisory / Consultancy, Research grant / Funding (institution): Ascentage; Advisory / Consultancy: Aximmune; Advisory / Consultancy: Bayer; Advisory / Consultancy: BioInvent; Advisory / Consultancy, Research grant / Funding (institution): Birdie; Advisory / Consultancy: Boston Bio; Advisory / Consultancy: EMD Serono; Advisory / Consultancy: Forbius; Advisory / Consultancy: HBM Partners; Advisory / Consultancy: Ignyta; Advisory / Consultancy: Immunome; Advisory / Consultancy: Immunomet; Advisory / Consultancy: Jazz; Advisory / Consultancy: Mekanistic; Advisory / Consultancy: Nanobiotix; Advisory / Consultancy: NBE Therapeutics; Advisory / Consultancy: Nuvalent; Advisory / Consultancy: Pelican; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Ridgeway; Advisory / Consultancy: Scitemex; Advisory / Consultancy: Sesen; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: Sunshine Guojian; Advisory / Consultancy, Research grant / Funding (institution): Symphogen; Advisory / Consultancy: Syneos; Research grant / Funding (institution): Aminex; Research grant / Funding (institution): Asana; Research grant / Funding (institution): Arrys; Research grant / Funding (institution): CStone; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Inhibrx; Research grant / Funding (institution): Innate; Research grant / Funding (institution): Kiromie; Research grant / Funding (institution): Mersana; Research grant / Funding (institution): NatureWise; Research grant / Funding (institution): NextCure; Research grant / Funding (institution): NittoBiopharma; Research grant / Funding (institution): Pieris; Research grant / Funding (institution): Syndax; Research grant / Funding (institution): Tizone; Research grant / Funding (institution): Zymeworks. G. Falchook: Licensing / Royalties: Wolters Kluwer; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Fujifilm; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: EMD Serono; Travel / Accommodation / Expenses: Bristol-Myers Squibb; Research grant / Funding (institution), Travel / Accommodation / Expenses: Millennium; Speaker Bureau / Expert testimony: Total Health Conferencing; Research grant / Funding (institution): 3-V Biosciences; Research grant / Funding (institution): Abbvie; Research grant / Funding (institution): ADC Therapeutics; Research grant / Funding (institution): Aileron; Research grant / Funding (institution): American Society of Clinical Oncology; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): ARMO; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): BeiGene; Research grant / Funding (institution): Bioatla; Research grant / Funding (institution): Biothera; Research grant / Funding (institution): Celldex; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Ciclomed; Research grant / Funding (institution): Curegenix; Research grant / Funding (institution): Curis; Research grant / Funding (institution): DelMar; Research grant / Funding (institution): eFFECTOR; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Exelixis; Research grant / Funding (institution): Genmab; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Hutchinson MediPharma; Research grant / Funding (institution): Ignyta; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Jacobio; Research grant / Funding (institution): Jounce; Research grant / Funding (institution): Kolltan; Research grant / Funding (institution): Loxo; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Merck; Research grant / Funding (institution): miRNA Therapeutics; Research grant / Funding (institution): National Institutes of Health; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): OncoMed; Research grant / Funding (institution): Oncothyreon; Research grant / Funding (institution): Precision Oncology; Research grant / Funding (institution): Regeneron; Research grant / Funding (institution): Rgenix; Research grant / Funding (institution): Strategia; Research grant / Funding (institution): Syndax; Research grant / Funding (institution): Taiho; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Tarveda; Research grant / Funding (institution): Tesaro; Research grant / Funding (institution): Tocagen; Research grant / Funding (institution): U.T. MD Anderson Cancer Center; Research grant / Funding (institution): Vegenics. J.C. Bendell: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Gilead; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Research grant / Funding (institution): Five Prime; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: MedImmune; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Research grant / Funding (institution): EMD Serono; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Taiho; Advisory / Consultancy, Research grant / Funding (institution): Macrogenics; Advisory / Consultancy, Research grant / Funding (institution): GSK; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: OncoMed; Advisory / Consultancy, Research grant / Funding (institution): LEAP; Advisory / Consultancy, Research grant / Funding (institution): TG Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BI; Advisory / Consultancy, Research grant / Funding (institution): Daiichi Sankyo; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): Incyte; Advisory / Consultancy, Research grant / Funding (institution): Apexigen; Research grant / Funding (institution): Koltan; Research grant / Funding (institution): SynDevRex; Research grant / Funding (institution): Forty Seven; Research grant / Funding (institution): AbbVie; Advisory / Consultancy, Research grant / Funding (institution): Array; Research grant / Funding (institution): Onyx; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Celldex; Research grant / Funding (institution): Agios; Research grant / Funding (institution): Cytomax; Research grant / Funding (institution): Nektar; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: ARMO; Research grant / Funding (institution): Boston Biomedical; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy, Research grant / Funding (institution): Merrimack; Research grant / Funding (institution): Tarveda; Research grant / Funding (institution): Tyrogenex; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Oncogenex; Research grant / Funding (institution): Marshall Edwards; Research grant / Funding (institution): Pieris; Research grant / Funding (institution): Mersana; Research grant / Funding (institution): Calithera; Research grant / Funding (institution): Blueprint; Research grant / Funding (institution): Evelo; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: FORMA; Research grant / Funding (institution): Merus; Research grant / Funding (institution): Jacobio; Research grant / Funding (institution): Effector; Research grant / Funding (institution): Novocare; Research grant / Funding (institution): Arrys; Research grant / Funding (institution): Tracon; Research grant / Funding (institution): Sierra; Advisory / Consultancy, Research grant / Funding (institution): Innate; Advisory / Consultancy, Research grant / Funding (institution): Arch Oncology; Research grant / Funding (institution): Prelude Oncology; Research grant / Funding (institution): Unum Therapeutics; Research grant / Funding (institution): Vyriad; Research grant / Funding (institution): Harpoon; Research grant / Funding (institution): ADC; Advisory / Consultancy, Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Millennium; Research grant / Funding (institution): Imclone; Research grant / Funding (institution): Acerta Pharma; Research grant / Funding (institution): Rgenix; Research grant / Funding (institution): Bellicum; Advisory / Consultancy: Prelude Therapeutics; Advisory / Consultancy: Phoenix Bio; Advisory / Consultancy: Cyteir; Advisory / Consultancy: Molecular Partners; Advisory / Consultancy: Torque; Advisory / Consultancy: Tizona; Advisory / Consultancy: Janssen; Advisory / Consultancy: Tolero; Advisory / Consultancy: TD2 (Translational Drug Development); Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: Moderna Therapeutics; Advisory / Consultancy: Tanabe Research Laboratories; Advisory / Consultancy: Beigene; Advisory / Consultancy: Continuum Clinical; Advisory / Consultancy: Agois; Advisory / Consultancy: Kyn. D. Ungar: Full / Part-time employment: ADC Therapeutics. J. Boni: Full / Part-time employment: ADC Therapeutics America. G. Chao: Shareholder / Stockholder / Stock options, Full / Part-time employment: ADCT. M.R. Patel: Advisory / Consultancy, Speaker Bureau / Expert testimony: Exelixis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Genentech; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pharmacyclics; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Janssen; Advisory / Consultancy, Speaker Bureau / Expert testimony: Celgene.
Resources from the same session
3305 - A phase I dose-escalation and expansion trial of intratumorally administered CV8102, alone and in combination with anti-PD-1 in patients with advanced solid tumors
Presenter: Jürgen Krauss
Session: Poster Display session 1
Resources:
Abstract
5353 - Phase 1/2 Study of 9-ING-41, a small molecule selective Glycogen Synthase Kinase-3 Beta (GSK-3β) Inhibitor, as a Single Agent and Combined with Chemotherapy, in Patients with Refractory Hematological Malignancies or Solid Tumors
Presenter: Benedito Carneiro
Session: Poster Display session 1
Resources:
Abstract
3946 - Trial in progress: a Phase I, open-label study of GSK1795091 administered in combination with immunotherapies in participants with advanced solid tumors (NCT03447314).
Presenter: Aaron Hansen
Session: Poster Display session 1
Resources:
Abstract
3449 - Radiographic Phenotyping to Identify Intracranial Disseminated Recurrence in Brain metastases Treated With Radiosurgery Using Contrast-enhanced MR Imaging
Presenter: CheYu Hsu
Session: Poster Display session 1
Resources:
Abstract
4553 - Association between TP53 mutations and efficacy of Osimertinib for brain metastasis from EGFR-mutant lung cancer
Presenter: Lijuan Chen
Session: Poster Display session 1
Resources:
Abstract
4942 - Response assessment of melanoma brain metastases treated by stereotactic radiotherapy or immunotherapy or both: a comparison of RECIST 1.1, RANO and iRANO criteria
Presenter: Emilie Le Rhun
Session: Poster Display session 1
Resources:
Abstract
3529 - Management of multiple brain metastases by Staged SRS focusing on utmost risk lesions
Presenter: shaoqun Li
Session: Poster Display session 1
Resources:
Abstract
5315 - Whole brain radiotherapy plus simultaneous in-field boost versus whole brain radiotherapy plus fractionated stereotactic radiotherapy for multiple brain metastases of non-small cell lung cancer
Presenter: Lu Li
Session: Poster Display session 1
Resources:
Abstract
1116 - 3D based texture analysis serving as potential diagnostic factor in discriminating primary central nervous system lymphoma from metastatic brain tumors: A preliminary study
Presenter: Wen Guo
Session: Poster Display session 1
Resources:
Abstract
5344 - Global trends in population-based survival for 303,169 adults diagnosed with glioblastoma in 44 countries during 2000-2014 (CONCORD-3)
Presenter: Fabio Girardi
Session: Poster Display session 1
Resources:
Abstract