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
1842 - Immunological impact of surgery in NSCLC patients
Presenter: Akitoshi Yanagihara
Session: Poster Display session 1
Resources:
Abstract
4124 - The prognostic value of selected immunological panel in predicting the prognosis of early-stage resectable non-small cell lung cancer
Presenter: Sha Zhao
Session: Poster Display session 1
Resources:
Abstract
4468 - Genomic Heterogeneity and Clonality Analysis of Multiple synchronous lung cancers (MSLCs)
Presenter: Fachen Zhou
Session: Poster Display session 1
Resources:
Abstract
5547 - Analysis of immunosuppressive factors produced by tumorspheres in NSCLC. Prognostic value of Galectin-3 in adenocarcinoma
Presenter: Susana Torres Martinez
Session: Poster Display session 1
Resources:
Abstract
1658 - Frequency of epidermal growth factor receptor (EGFR) mutations in stage IB–IIIA EGFR mutation positive non-small-cell lung cancer (NSCLC) after complete tumour resection
Presenter: Masahiro Tsuboi
Session: Poster Display session 1
Resources:
Abstract
1535 - EGFR mutation is not a prognostic factor in completely resected lymph node–negative pulmonary adenocarcinoma (LNNPA)
Presenter: Nussara Leeladejkul
Session: Poster Display session 1
Resources:
Abstract
3262 - Prognostic significance of elements of the adaptive immunity in the microenvironment of early-stage non small cell lung cancer
Presenter: Aliki Liakea
Session: Poster Display session 1
Resources:
Abstract
4643 - Combined immunoscore for prognostic stratification of early stage NSCLC patients
Presenter: Giulia Pasello
Session: Poster Display session 1
Resources:
Abstract
4819 - Radiation-induced lung injury and misdiagnosis rate after SBRT
Presenter: Xiaolong Fu
Session: Poster Display session 1
Resources:
Abstract
681 - Significance of the red blood cell distribution width in resected pathological stage I non-small cell lung cancer
Presenter: Gouji Toyokawa
Session: Poster Display session 1
Resources:
Abstract