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
3993 - Prophylaxis with Lipegfilgrastim in patients with primary breast cancer receiving dose dense chemotherapy: results from the German NIS NADENS
Presenter: Marion Kiechle
Session: Poster Display session 1
Resources:
Abstract
3471 - Randomized phase 2 trial evaluating the safety of peripherally inserted central catheters vs implanted port catheters during adjuvant chemotherapy in early breast cancer patients.
Presenter: Florian Clatot
Session: Poster Display session 1
Resources:
Abstract
1327 - Simultaneous intravenous fluid infusion to prevent oxaliplatin infusion-related venous pain
Presenter: Stefan Van Ravensteijn
Session: Poster Display session 1
Resources:
Abstract
5004 - Clinical practice evaluation of opioids induced constipation management in cancer patients: The EIO-Praxis project.
Presenter: Enrique Aranda Aguilar
Session: Poster Display session 1
Resources:
Abstract
2222 - Analysis of the efficacy of naloxegol in a real-world 12 weeks of follow-up study, in patients with cancer and opioid-induced constipation with laxative-inadequate response.
Presenter: Manuel Cobo Dols
Session: Poster Display session 1
Resources:
Abstract
5556 - Consensus on strategies in the management of opioid-induced constipation in cancer patients
Presenter: Regina Girones Sarrio
Session: Poster Display session 1
Resources:
Abstract
3913 - Effect of Chinese Herbal Compound LC09 on Patients With Capecitabine-Associated Hand-Foot Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial
Presenter: Yanni Lou
Session: Poster Display session 1
Resources:
Abstract
2208 - A prospective study about the complementary medicine among patients with cancers
Presenter: Wala Ben Kridis
Session: Poster Display session 1
Resources:
Abstract
1082 - Prevalence and management of Potentially Inappropriate Medication use and Potential Omissions in Medication in older cancer patients - the PIM POM study
Presenter: Fianne van Loveren
Session: Poster Display session 1
Resources:
Abstract
1701 - Immunogenicity and optimal timing of 13-valent pneumococcal conjugate vaccination during adjuvant chemotherapy in gastric and colorectal cancer : A randomized controlled trial
Presenter: Wonyoung Choi
Session: Poster Display session 1
Resources:
Abstract