Abstract 5136
Background
Maintenance PARPis are standard of care for pts with recurrent ovarian cancer. Optimal treatment following PARPi resistance is currently unknown. PARPi-resistant recurrent ovarian cancer with expected platinum sensitivity is associated with high mutational load and homologous recombination deficiency. Ataxia telangiectasia and rad3-related (ATR) inhibition combined with immune checkpoint inhibition and DNA-damaging agents, such as carboplatin, has potential for activity following PARPi resistance by increasing DNA damage, immunologic cell death and potential immunological targets.
Trial design
NCT03704467 is an open-label, multicentre, international, 2-part study including participants with PARPi-resistant, recurrent epithelial ovarian, primary peritoneal or fallopian tube cancer. Pts must have received ≥2 platinum-based tx (and responded to the last platinum-based tx); last platinum dose ≥ 6 months prior; ≥4 months PARPi maintenance tx before progression (PD) and known BRCA1/2 mutation status. Part A is a safety run-in, with dose de-escalation to find a recommended phase 2 dose (RP2D) of 3weekly carboplatin + M6620 (an ATR inhibitor) + avelumab (a programmed death ligand-blocking mAB; all iv). Planned starting doses are carboplatin AUC 5; M6620 90 mg/m2; avelumab 1600 mg. In Part B, pts will be randomized (stratified by BRCA gene status) to carboplatin + M6620 (at the RP2D from Part A) + avelumab or SC (platinum-based doublet ± bevacizumab; investigator’s choice). After completion of ≤ 6 triplet cycles in Part A/B, pts can receive avelumab maintenance tx (800 mg every 2 weeks) until PD, unacceptable toxicity, withdrawal of consent, death, or ≥ 12 months tx following confirmed complete response. The primary objective of Part B is progression-free survival. Secondary objectives for Part A/B include safety/tolerability; pharmacokinetics, immunogenicity, antitumor activity (BOR, duration of response, time to progression/subsequent tx). Planned enrolment: Part A 3–18 pts (modified 3 + 3 design); Part B ∼72 pts. Enrolment began in Nov 2018 and the first patient is enrolled.
Clinical trial identification
NCT03704467.
Editorial acknowledgement
Lisa Jolly, PhD, of Bioscript Science Macclesfield, UK, funded by Merck KGaA, Darmstadt, Germany.
Legal entity responsible for the study
Merck KGaA.
Funding
Merck KGaA.
Disclosure
S. Banerjee: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self): Tesaro; Honoraria (self): Clovis; Honoraria (self): Merck Serono; Honoraria (self): Nucana; Honoraria (self): Immunogen; Honoraria (self): Seattle Genetics; Honoraria (self): Roche; Honoraria (self): Gamamabs. I. Vergotte: Advisory / Consultancy: Advaxis, Inc.; Advisory / Consultancy: Eisai Inc.; Advisory / Consultancy: MSD Belgium; Advisory / Consultancy: Roche NV; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Genmab; Advisory / Consultancy: F. Hoffmann-La Roche Ltd; Advisory / Consultancy, Travel / Accommodation / Expenses: PharmaMar; Advisory / Consultancy: Millennium Pharmaceuticals; Advisory / Consultancy: Clovis Oncology Inc.; Advisory / Consultancy: AstraZeneca NV; Advisory / Consultancy, Travel / Accommodation / Expenses: Tesaro; Advisory / Consultancy, Research grant / Funding (institution): Oncoinvent AS; Advisory / Consultancy: Immunogen Inc; Advisory / Consultancy: Sotio; Research grant / Funding (institution): Amgen; Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution): Stichting tegen Kanker; Travel / Accommodation / Expenses: Takeda Oncology; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Clovis; Travel / Accommodation / Expenses: Immunogen. N. Colombo: Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: PharmaMar; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Tesaro; Advisory / Consultancy: Clovis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: MSD; Advisory / Consultancy: BIOCAD; Advisory / Consultancy: Takeda; Advisory / Consultancy: Lilly; Leadership role, Subject Editor: ESMO Clinical Guidelines; Non-remunerated activity/ies, Chair Scientific Committee: ACTO Onlus. R. Grisham: Advisory / Consultancy: Clovis; Advisory / Consultancy: Mateon. K.T. Mehr: Full / Part-time employment: Merck KGaA. M. Falk: Full / Part-time employment: Merck KGaA. F. Beier: Full / Part-time employment: Merck KGaA. M. Hennessy: Full / Part-time employment: EMD Serono. A. Schroeder: Full / Part-time employment: Merck KGaA. All other authors have declared no conflicts of interest.
Resources from the same session
4317 - Prognostic factors analysis of 343 patients with adenocarcinoma of esophagogastric junction
Presenter: Yixun Lu
Session: Poster Display session 2
Resources:
Abstract
4099 - Effects of preoperative preparation time on efficacy of neoadjuvant chemotherapy (SOX) in patients with advanced gastric cancer
Presenter: Xinxin Wang
Session: Poster Display session 2
Resources:
Abstract
3769 - The prognostic value of higher absolute lymphocyte counts for patients with surgically resected non-advanced gastric cancer
Presenter: Se Jun Park
Session: Poster Display session 2
Resources:
Abstract
1718 - Trastuzumab and pertuzumab added to neoadjuvant chemoradiotherapy in resectable HER2+ esophageal adenocarcinoma patients: an update on survival and predictive biomarkers in the TRAP study
Presenter: Charlotte Stroes
Session: Poster Display session 2
Resources:
Abstract
5403 - Interim analysis of a phase II trial of perioperative chemotherapy plus avelumab in esophagogastric and gastric adenocarcinoma
Presenter: Thierry Alcindor
Session: Poster Display session 2
Resources:
Abstract
591 - Evaluation of the introduction of primary G-CSF prophylaxis to the FLOT chemotherapy regimen.
Presenter: Kelly-Marie Crampton
Session: Poster Display session 2
Resources:
Abstract
1402 - Subgroup analyses of a randomized two-by-two factorial phase II trial comparing neoadjuvant chemotherapy with 2 and 4 courses of cisplatin/S-1 (CS) and docetaxel/cisplatin/S-1 (DCS) as neoadjuvant chemotherapy for locally advanced gastric cancer
Presenter: Tsutomu Hayashi
Session: Poster Display session 2
Resources:
Abstract
3743 - HER2 Copy Number as Predictor of Disease-Free Survival in HER2-Positive Resectable Gastric Cancer
Presenter: Zimin Liu
Session: Poster Display session 2
Resources:
Abstract
2032 - Effect of neoadjuvant chemotherapy on the Programmed Death-1 pathway in esophageal and gastric cancer
Presenter: Maria Svensson
Session: Poster Display session 2
Resources:
Abstract
4304 - A user-friendly nomogram to predict relapse-free survival (RFS) in western patients with resected gastric cancer (GC)
Presenter: Massimiliano Salati
Session: Poster Display session 2
Resources:
Abstract