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
5629 - Outcome of triple negative inflammatory breast cancers (TNIBC) treated with dose dense neoadjuvant epirubicin cyclophosphmide, prognostic impact of pre and post neoadjuvant chemotherapy (NAC) tumor infiltrating lymphocytes (TIL) and post NAC lymphovascular invasion
Presenter: Luca Campedel
Session: Poster Display session 2
Resources:
Abstract
5792 - A novel PET parameter for cancer stem cell metabolism: early prediction of chemosensitivity to neoadjuvant chemotherapy in locally advanced breast cancer
Presenter: Chanwoo Kim
Session: Poster Display session 2
Resources:
Abstract
3728 - Using nodal ratio to predict recurrence in patients with 4 or more positive lymph nodes early stage breast cancer
Presenter: Besma Graja
Session: Poster Display session 2
Resources:
Abstract
3395 - Re-sentinel node biopsy for local recurrence after breast-conserving surgery
Presenter: Yuka Matsubara
Session: Poster Display session 2
Resources:
Abstract
4302 - Assessment of prognostic and therapeutic factors in men with breast cancer
Presenter: Daniel Herrero Rivera
Session: Poster Display session 2
Resources:
Abstract
4263 - Genomic Profiling of Chinese Breast Cancer Patients
Presenter: Zhonghua Tao
Session: Poster Display session 2
Resources:
Abstract
2406 - Genome copy number alteration burden represents predictor of response in long-term, never relapse exceptional responders of trastuzumab-treated HER2+ metastatic breast cancer
Presenter: Naomi Walsh
Session: Poster Display session 2
Resources:
Abstract
2575 - Next-generation DNA Sequencing (NGS) Results for Tumors From Phase 2 ABRAZO Study of Talazoparib After Platinum or Cytotoxic Non-Platinum Regimens in Patients (pts) With Advanced Breast Cancer (ABC) and Germline BRCA1/2 (gBRCA) Mutations
Presenter: Nicholas C. Turner
Session: Poster Display session 2
Resources:
Abstract
4499 - FGFR1 and CCND1 gene amplifications are associated with breast cancer resistance to aromatase inhibitors
Presenter: Evgeny Imyanitov
Session: Poster Display session 2
Resources:
Abstract
4110 - Clinicopathologic features of BRCA mutated breast cancer patients: Hacettepe Experience
Presenter: Sercan Aksoy
Session: Poster Display session 2
Resources:
Abstract