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
3139 - Efficacy and safety of FOLFIRI/Aflibercept (FA) in elderly population with mCRC after failure of oxaliplatin-based chemotherapy.
Presenter: Nieves Martinez Lago
Session: Poster Display session 2
Resources:
Abstract
3446 - Fluoropyrimidine-induced cardiotoxicity in colorectal cancer patients: preliminary data from the prospective observational CHECKPOINT trial (NCT02665312)
Presenter: Pasquale Lombardi
Session: Poster Display session 2
Resources:
Abstract
3969 - Comparable survival outcome between Thai patients with sporadic young adult and adult onset colorectal cancer
Presenter: Kanjana Sukhokanjanachusak
Session: Poster Display session 2
Resources:
Abstract
4455 - Impact of primary tumor side on 3-year survival outcomes of first-line (1L) FOLFOX-4 ± cetuximab in patients with RAS wild-type (wt) metastatic colorectal cancer (mCRC) in the phase 3 TAILOR trial
Presenter: Shukui Qin
Session: Poster Display session 2
Resources:
Abstract
4481 - Undetectable RAS mutant clones in plasma: possible implication for therapy and prognosis in the patient with RAS mutant metastatic colorectal cancer?
Presenter: Mohamed Bouchahda
Session: Poster Display session 2
Resources:
Abstract
5074 - Dihydropyrimidine dehydrogenase (DPD) determination prior the administration of medicines containing fluorouracil: a single Spanish hospital experience.
Presenter: Maria Dolores Mediano Rambla
Session: Poster Display session 2
Resources:
Abstract
5242 - Differences in survival between right and left-sided colorrectal cancer (CRC) in every stage, a CARESS-CCR Group Study.
Presenter: Julia Alcaide-Garcia
Session: Poster Display session 2
Resources:
Abstract
1123 - Quality of Life (QoL) in patients with aflibercept (AFL) and FOLFIRI for metastatic colorectal cancer (mCRC) – Interim analysis with focus on mutational status of the non-interventional study QoLiTrap (AIO-LQ-0113)
Presenter: Roger von Moos
Session: Poster Display session 2
Resources:
Abstract
1212 - The cost of adverse event management in patients with RAS wild-type metastatic colorectal cancer treated with first-line cetuximab and panitumumab: an Italian healthcare payer perspective
Presenter: Karl Patterson
Session: Poster Display session 2
Resources:
Abstract
1619 - Meta-analysis of KRAS Mutation as prognostic factor in patients (pts.) with resection of colorectal (CRC) liver metastases: Tumor burden and Sideness analysis.
Presenter: Maria Romina Luca
Session: Poster Display session 2
Resources:
Abstract