Abstract 4584
Background
ABBV-621, a tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor agonist, induces cell death in tumor cells by activation of death receptor 4 and 5. Maximum tolerated dose was not reached in dose escalation (Ratain et al. ASCO 2019; NCT03082209). Herein is reported the analysis of safety and antitumor activity in additional pts enrolled in the dose-optimization cohorts with the goal of identifying the recommended phase 2 dose.
Methods
Eligible pts (≥18 years, relapsed/refractory [R/R] KRAS-mutant colorectal [CRC] or pancreatic cancer, ECOG 0–2, measurable disease, willingness to undergo mandatory biopsies) received ABBV-621 intravenously (1.25–7.5 mg/kg) on day (D) 1, D8, and D15 of a 21-D cycle. Analyzed tumor types were evenly distributed across dose levels (DL).
Results
As of 16 Apr 2019, 48 pts received ≥1 dose of ABBV-621 (CRC, n = 24/pancreatic, n = 24; 1.25 mg/kg, n = 8/8; 3.75 mg/kg, n = 8/8; 7.5 mg/kg, n = 8/8). Median age: 63 years (range, 43–76); 65% male, 73% ≥3 prior treatment (Tx) regimens. Median duration of ABBV-621 exposure was 36 days (range, 1–251) with a median 2 Tx cycles (range, 1–12). Tx-emergent and Tx-related AEs are summarized in the table. Ten pts (20.8%) experienced AEs leading to discontinuation; 4 (9.3%) pts had dose-limiting toxicities possibly associated with ABBV-621 administration: respiratory failure (7.5 mg/kg; Grade 5, the only Tx-related death), increased ALT and AST (1.25, 3.75 mg/kg), toxic hepatitis (1.25 mg/kg), non-cardiac chest pain (1.25 mg/kg), and pleuritic pain (1.25 mg/kg). ALT, alanine aminotransferase; AST, aspartate aminotransferase A partial response was observed in 1 pt with CRC (1.25 mg/kg) and 1 pt with pancreatic cancer (3.75 mg/kg). Stable disease at 12 weeks was the best response in 20 pts (41.7%; CRC, n = 9/pancreatic, n = 11).Table:
457P
AEs, n (%) | Related to ABBV-621, n (%) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
All grade (≥5 patients) | Grade 3/4 | Serious | ||||||||||
1.25 mg/kg (n = 16) | 3.75 mg/kg (n = 16) | 7.5 mg/kg (n = 16) | Total (N = 48) | 1.25 mg/kg (n = 16) | 3.75 mg/kg (n = 16) | 7.5 mg/kg (n = 16) | Total (N = 48) | 1.25 mg/kg (n = 16) | 3.75 mg/kg (n = 16) | 7.5 mg/kg (n = 16) | Total (N = 48) | |
Fatigue | 4 (25.0) | 3 (18.8) | 4 (25.5) | 11 (22.9) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Increased ALT | 1 (6.3) | 4 (25.0) | 5 (31.3) | 10 (20.8) | 1 (6.3) | 1 (6.3) | 1 (6.3) | 3 (6.3) | 0 | 1 (6.3) | 0 | 1 (2.1) |
Stomatitis | 1 (6.3) | 3 (18.8) | 5 (31.3) | 9 (18.8) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Increased AST | 1 (6.3) | 3 (18.8) | 4 (25.0) | 8 (16.7) | 1 (6.3) | 1 (6.3) | 2 (12.5) | 4 (8.3) | 0 | 1 (6.3) | 0 | 1 (2.1) |
Decreased appetite | 2 (12.5) | 1 (6.3) | 4 (25.0) | 7 (14.6) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Diarrhea | 1 (6.3) | 3 (18.8) | 3 (18.8) | 7 (14.6) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Nausea | 2 (12.5) | 1 (6.3) | 4 (25.0) | 7 (14.6) | 0 | 0 | 0 | 0 | 0 | 0 | 1 (6.3) | 1 (2.1) |
Vomiting | 3 (18.8) | 1 (6.3) | 3 (18.8) | 7 (14.6) | 0 | 0 | 0 | 0 | 0 | 0 | 1 (6.3) | 1 (2.1) |
Dysgeusia | 2 (12.5) | 2 (12.5) | 1 (6.3) | 5 (10.4) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Pyrexia | 0 | 1 (6.3) | 4 (25.0) | 5 (10.4) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Conclusions
Administration of ABBV-621 in pts with R/R CRC and pancreatic cancer shows an acceptable safety profile at all DL and evidence of antitumor activity.
Clinical trial identification
NCT03082209.
Editorial acknowledgement
Medical writing support was provided by Yanci M. Baker, PhD, from Aptitude Health, Atlanta, GA, and funded by AbbVie.
Legal entity responsible for the study
AbbVie Inc.
Funding
AbbVie Inc.
Disclosure
E. Calvo: Honoraria (self): HM Hospitales Group; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Nanobiotix; Advisory / Consultancy: Janssen-Cilag; Advisory / Consultancy: PsiOxus; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: EUSA Pharma, Inc.; Advisory / Consultancy: AbbVie; Advisory / Consultancy: Celgene; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Guidepoint Global; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche/Genentech; Advisory / Consultancy: Gerson Lehrman Group; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Servier; Advisory / Consultancy: amcure; Leadership role: Foundation INTHEOS; Research grant / Funding (institution): BeiGene; Research grant / Funding (institution), Shareholder / Stockholder / Stock options: START; Shareholder / Stockholder / Stock options: Oncoart Associated; Shareholder / Stockholder / Stock options: International Cancer Consultants. M.J.A. de Jonge: Advisory / Consultancy: Faron Pharmaceutical Ltd. D.W. Rasco: Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Lily; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Millennium; Research grant / Funding (institution): Rexahn; Research grant / Funding (institution): Five Prime Therapeutics; Research grant / Funding (institution): Pharmacyclics; Research grant / Funding (institution), Travel / Accommodation / Expenses: Asana BioSciences; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Aeglea; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Ascentage; Research grant / Funding (institution): MacroGenics; Research grant / Funding (institution): Apexian; Research grant / Funding (institution): Birdie; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Constellation; Research grant / Funding (institution): Syndax; Research grant / Funding (institution): Astex; Research grant / Funding (institution): Compugen; Research grant / Funding (institution): Coordination; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Incyte. V. Moreno: Advisory / Consultancy: Puma Biotechnology; Travel / Accommodation / Expenses: Sanofi; Travel / Accommodation / Expenses: Regeneron. Y. Chang: Shareholder / Stockholder / Stock options, Full / Part-time employment: AbbVie. M. Chiney: Full / Part-time employment, Former employee: AbbVie; Full / Part-time employment, Current employee: Bristol-Myers Squibb. M. Motwani: Shareholder / Stockholder / Stock options, Full / Part-time employment: AbbVie. S. Penugonda: Shareholder / Stockholder / Stock options, Full / Part-time employment: AbbVie. A.M. Petrich: Shareholder / Stockholder / Stock options, Full / Part-time employment: AbbVie. M.J. Ratain: Advisory / Consultancy: Acentage Pharma; Advisory / Consultancy: Cyclacel; Advisory / Consultancy: Aptevo Therapeutics; Advisory / Consultancy: Shionogi; Research grant / Funding (institution): Dicerna; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Genentech/Roche; Licensing / Royalties: UGT1A1 genotyping for irinotecan; Licensing / Royalties: Genomic prescribing system; Officer / Board of Directors: Value in Cancer Care Consortium. P. LoRusso: Advisory / Consultancy: Agios; Advisory / Consultancy: AbbVie; Advisory / Consultancy: Genmab; Advisory / Consultancy: Halozyme; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: CytomX; Advisory / Consultancy: Five Prime; Advisory / Consultancy: Takeda; Advisory / Consultancy: Sotio; Advisory / Consultancy: Cybrexa; Advisory / Consultancy: Agenus.
Resources from the same session
4242 - HIV, HBV and HCV screening practices in oncology: a cross-sectional interregional survey
Presenter: Isabelle Poizot-Martin
Session: Poster Display session 1
Resources:
Abstract
1267 - Genetic landscape of KEAP1 and NFE2L2 mutated cancers from the AACR GENIE database
Presenter: Mark Zaki
Session: Poster Display session 1
Resources:
Abstract
878 - β-arrestin1 is involved in the Ras-induced malignant transformation
Presenter: Takashi Shibano
Session: Poster Display session 1
Resources:
Abstract
4143 - Incidence of second cancer among PLWHIV: retrospective observational study of a series of 601 patients in the French CANCERVIH network
Presenter: Jean-Philippe Spano
Session: Poster Display session 1
Resources:
Abstract
5145 - A challenging task – Identifying carcinoma of unknown primary (CUP) patients according to ESMO guidelines: the CUPISCO trial experience
Presenter: Chantal Pauli
Session: Poster Display session 1
Resources:
Abstract
1737 - Incidence and Outcome of chronic lymphocytic leukemia with Deletion 17p: An Indian experience; challenges and opportunities
Presenter: Ajay Gogia
Session: Poster Display session 1
Resources:
Abstract
2596 - Driving solo? Investigation into collaborating mutations in SDH-deficient neoplasia
Presenter: Jonathan Killian
Session: Poster Display session 1
Resources:
Abstract
1499 - The potential of a novel antiangiogenic VEGFR1-D2 binding peptide in oncology therapeutics
Presenter: Afsaneh Sadre Momtaz
Session: Poster Display session 1
Resources:
Abstract
1775 - First-in-human phase I study of TAS-117, an allosteric AKT inhibitor, in patients with advanced solid tumors
Presenter: Mayu Yunokawa
Session: Poster Display session 1
Resources:
Abstract
3620 - Safety, efficacy, PK and PD biomarker results of the first-in-human study of mutant isocitrate dehydrogenase 1 (mIDH1) inhibitor BAY 1436032 in patients (pts) with mIDH1 advanced solid tumours
Presenter: Wolfgang Wick
Session: Poster Display session 1
Resources:
Abstract