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
5103 - CANOPY phase 3 program: Three studies evaluating canakinumab in patients with non-small cell lung cancer (NSCLC)
Presenter: Luis Paz-Ares
Session: Poster Display session 1
Resources:
Abstract
3666 - The Elderly Patient Individualized Chemotherapy (EPIC) trial, a study for an aged population of non-small cell lung cancer.
Presenter: Francesco Passiglia
Session: Poster Display session 1
Resources:
Abstract
4799 - KEYNOTE-495/KeyImPaCT: A Randomized, Biomarker-Directed, Phase 2 Trial of Pembrolizumab-Based Therapy for Non–Small Cell Lung Cancer (NSCLC)
Presenter: Martin Gutierrez
Session: Poster Display session 1
Resources:
Abstract
6035 - Safety, tolerability and activity of autologous T cells with enhanced T-cell receptors specific to NY ESO 1/LAGE 1a (GSK3377794) alone, or in combination with pembrolizumab, in advanced non small cell lung cancer: A Phase 1b/2a randomised pilot study
Presenter: Karen Reckamp
Session: Poster Display session 1
Resources:
Abstract
2176 - IFCT-1701 DICIPLE: a randomized phase 3 trial comparing continuation Nivolumab-Ipilimumab doublet immunotherapy until progression versus observation in patients with PDL1-positive stage IV Non-Small Cell Lung Cancer (NSCLC) after Nivolumab-Ipilimumab induction treatment
Presenter: Gerard Zalcman
Session: Poster Display session 1
Resources:
Abstract
2352 - ATALANTE-1 randomized phase 3 trial, OSE-2101 versus standard treatment as second or third line in HLA-A2 positive advanced non-small cell lung cancer (NSCLC) patients
Presenter: Enriqueta Felip
Session: Poster Display session 1
Resources:
Abstract
2451 - Phase Ib dose-escalation/expansion study of BI 836880, a VEGF/Ang2-blocking nanobody®, in combination with BI 754091, an anti-PD-1 antibody, in patients with advanced solid tumours
Presenter: Nicolas Girard
Session: Poster Display session 1
Resources:
Abstract
4285 - Radiosurgery followed by Tumor Treating Fields (TTFields) for brain metastases (1-10) from NSCLC in the phase 3 METIS trial
Presenter: Minesh Mehta
Session: Poster Display session 1
Resources:
Abstract
4909 - Nivolumab plus ipilimumab (NI) versus chemotherapy plus nivolumab (CN) in squamous cell lung cancer (SqCLC): the SQUINT trial
Presenter: Lorenza Landi
Session: Poster Display session 1
Resources:
Abstract
4125 - DUBLIN-3, a Stage IIIb/IV NSCLC Phase (Ph)3 Trial Comparing the Plinabulin (P)/Docetaxel(D) Combination with D Alone
Presenter: Ramon Mohanlal
Session: Poster Display session 1
Resources:
Abstract