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
2066 - Second-line (2L) real-world treatment (tx) patterns and outcomes in patients (pts) with advanced/metastatic non-small cell lung cancer (NSCLC) treated with first line (1L) immuno-oncology (IO) monotherapy (mono tx)
Presenter: Denis Talbot
Session: Poster Display session 1
Resources:
Abstract
5919 - Real-world effectiveness of nivolumab monotherapy after prior systemic therapy in advanced non-small cell lung cancer (NSCLC) in the United States
Presenter: David Stenehjem
Session: Poster Display session 1
Resources:
Abstract
3368 - Pembrolizumab as first-line treatment in NSCLC with PD-L1 ≥50%: Real life results from an all-comer population
Presenter: Nikolaj Frost
Session: Poster Display session 1
Resources:
Abstract
3775 - Patients with metastatic non-small cell lung cancer without molecular alterations or PD-L1 expression in Germany. Treatment and first outcome from the prospective German Registry Platform CRISP (AIO-TRK-0315)
Presenter: Frank Griesinger
Session: Poster Display session 1
Resources:
Abstract
3926 - Impact of second-line (2L) immune checkpoint inhibitors (ICIs) on the treatment (Tx) of advanced non-small cell lung cancer (NSCLC) in a UK centre: a REAL-Oncology analysis from the I-O Optimise initiative
Presenter: Michael Snee
Session: Poster Display session 1
Resources:
Abstract
5068 - First line pembrolizumab for NSCLC with PD-L1 TPS > 50% in a first French real life cohort
Presenter: Karim Amrane
Session: Poster Display session 1
Resources:
Abstract
1182 - Interstitial lung disease induced by immune-checkpoint inhibitors correlates with prognosis of advanced non-small-cell lung cancer patients
Presenter: Teppei Sugano
Session: Poster Display session 1
Resources:
Abstract
2297 - Phase II study to evaluate the peripheral blood mononuclear cell biomarker for nivolumab efficacy on previously treated non-small cell lung cancer subjects (NEJ029B: IMMUNITY-ONE)
Presenter: Yosuke Kawashima
Session: Poster Display session 1
Resources:
Abstract
2739 - Efficacy and safety of nintedanib + docetaxel in lung adenocarcinoma patients (pts) following treatment with immune checkpoint inhibitors (ICIs): Updated results of the ongoing non-interventional study (NIS) VARGADO (NCT02392455)
Presenter: Christian Grohe
Session: Poster Display session 1
Resources:
Abstract
1357 - Upfront atezolizumab chemoimmunotherapy-associated Immune-related adverse events in patients with advanced non-small cell lung cancer
Presenter: Francis Mogollon-Duffo
Session: Poster Display session 1
Resources:
Abstract