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
5638 - Incidence of Vascular Thromboembolism Events in Cancer Patients Receiving Immunotherapy: A Single Institution Experience.
Presenter: Laura Gutiérrez Sainz
Session: Poster Display session 1
Resources:
Abstract
5182 - High Incidence of Venous Thromboembolic Events (VTE) in Patients with Diffuse Large B-Cell Lymphoma.
Presenter: Alaa Abufara
Session: Poster Display session 1
Resources:
Abstract
1504 - Weight Loss over Time in Non-Small Cell Lung Cancer: Results from a Landmark Analysis of 800+ Prospectively-Treated Patients
Presenter: Jennifer Le-rademacher
Session: Poster Display session 1
Resources:
Abstract
3972 - The prognostic significance of preoperative nutritional status in resected pancreatic ductal adenocarcinoma (PDAC).
Presenter: Salvatore Paiella
Session: Poster Display session 1
Resources:
Abstract
2313 - Impact of Timing and Technique of Gastrostomy Placement on the Outcome of Patients (pts) with Head and Neck Cancer (HNC)
Presenter: M Julia Lostes Bardaji
Session: Poster Display session 1
Resources:
Abstract
5219 - Clinical & nutritional determinants of quality of life in patients with incurable cancer
Presenter: Louise Daly
Session: Poster Display session 1
Resources:
Abstract
4075 - Loss of skeletal muscle mass during palliative chemotherapy is a poor prognostic factor in patients with advanced gastric cancer
Presenter: In Gyu Hwang
Session: Poster Display session 1
Resources:
Abstract
4159 - Impact of nutritional derangement on treatment outcome in advanced non-small-cell lung cancer (A-NSCLC) patients (pts).
Presenter: Ilaria Trestini
Session: Poster Display session 1
Resources:
Abstract
1210 - Sarcopenia and pretreatment anemia as prognostic factors for patients with localized muscle invasive bladder cancer treated by neoadjuvant chemotherapy and radical cystectomy
Presenter: Emilien Billon
Session: Poster Display session 1
Resources:
Abstract
2490 - Gender effect on the pharmacokinetics (PK) and pharmacodynamics (PD) of anamorelin (ANAM) in healthy volunteers and cancer patients with cachexia
Presenter: Stein Kaasa
Session: Poster Display session 1
Resources:
Abstract