Abstract 727P
Background
We have shown that neoadjuvant carboplatin and paclitaxel (NACP) increased tumor-infiltrating lymphocytes and PDL1 expression in OC pts. Combined PDL1/CTLA4 blockade is active in relapsed OC. INEOV is the 1st trial of neoadjuvant D +/- T with NACP in pts with unresectable OC. Main endpoints are feasibility and safety. 2° endpoints include macroscopically complete resection (CCO) and major pathological response rates after 3 cycles (C3).
Methods
Pts with stage IIIC/IV OC were randomized to C1 of NACP alone (immune microenvironment priming) followed by NACP + D (1125mg) at C2&C3 without (arm A) or with T (75mg) at C2 (arm B). Interval debulking surgery (IDS) was planned after C3, or delayed after C6. Major pathological response after C3 was either a chemotherapy response score (CRS) of 3 (Bohm et al) or no viable tumor cells (pCR) at IDS. Data on delayed IDS are not yet available.
Results
Sixty six (N=66) pts (IIIC/IV: 70%/30%) were randomized. Treatment was feasible: 96% (32/36) and 88% (29/33) pts completed C1 to C3 in <9wks in arm A and B, respectively. Median interval between C3 and IDS was similar in both arms (34 days). Treatment was well tolerated: 41% of pts experienced at least one G3/4 adverse event (AE), mostly hematological attributable to NACP. There were only 6% G3/4 immune related AEs (3% vs 9% in arm A vs B), one case each: increased lipase, increased amylase, diabetes and diarrhea. IDS was performed in 39/64 evaluable pts and CCO achieved in 37 (95%) of them, for an overall CCO rate of 58% (37/64). CRS3 including 4 pCR and 2 extra-ovarian pCR was observed in 38% (15/39). There was no significant difference in AEs, CCO or major pathological response rates in arm A vs B.
Conclusions
We showed for the 1st time that the combination of D+/- T with NACP is feasible, safe and does not compromise chemotherapy delivery and efficacy. Major pathological responses were observed but the addition of T did not increase CCO or CRS3 rates. Studies are ongoing to describe longer-term outcomes including delayed IDS and PFS as well as the impact of treatment on the immune microenvironment in arm A vs B.
Clinical trial identification
EudraCT 2016-005229-35, NCT03249142.
Editorial acknowledgement
Legal entity responsible for the study
ARCAGY-GINECO.
Funding
AstraZeneca.
Disclosure
A. Leary: Financial Interests, Personal, Advisory Board: Zentalis; Financial Interests, Personal, Invited Speaker, Educational: GSK; Financial Interests, Personal, Invited Speaker, Educational: Medscape; Financial Interests, Personal, Invited Speaker, Educational: Onko+; Financial Interests, Institutional, Other, Steering committee: MSD; Financial Interests, Institutional, Advisory Board: GSK; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: Clovis; Financial Interests, Institutional, Invited Speaker, Educational: Kephren publishing; Financial Interests, Institutional, Advisory Board: Ability Pharma; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Other, Consultancy: Orion; Financial Interests, Institutional, Advisory Board: Tesaro; Financial Interests, Institutional, Invited Speaker: Tesaro; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Personal, Other, Consultancy: GLG; Financial Interests, Institutional, Advisory Board: Merck Serono; Financial Interests, Institutional, Invited Speaker: Clovis; Financial Interests, Institutional, Advisory Board: Apmonia; Financial Interests, Institutional, Research Grant, PI translational research: ARCAGY-GINECO; Financial Interests, Institutional, Research Grant, PI translational research: Sanofi; Financial Interests, Institutional, Research Grant, PI translational research: AstraZeneca; Financial Interests, Institutional, Funding, CI clinical trial: AstraZeneca; Financial Interests, Institutional, Research Grant, Int CI clinical trial: OSE immuno; Financial Interests, Institutional, Funding, PI clinical trial: Agenus; Financial Interests, Institutional, Funding, PI 5 clinical trials: Roche; Financial Interests, Institutional, Funding, PI clinical trial: BMS; Financial Interests, Institutional, Funding, PI 2 clinical trials: AstraZeneca; Financial Interests, Institutional, Funding, PI clinical trial: Iovance; Financial Interests, Institutional, Funding, PI 3 clinical trials and steering committee: MSD; Financial Interests, Institutional, Funding, PI clinical trial: GSK; Non-Financial Interests, Institutional, Other, Academic research project: Owkin; Non-Financial Interests, Institutional, Other, Academic research project: LXRepair; Non-Financial Interests, Personal, Proprietary Information, IDMC member: Clovis; Non-Financial Interests, Personal, Proprietary Information, IDMC chair: Pfizer. T. De La Motte Rouge: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Clovis Oncology; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Mylan; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Tesaro; Financial Interests, Institutional, Principal Investigator: AstraZeneca; Financial Interests, Institutional, Principal Investigator: GSK; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Principal Investigator: MSD; Financial Interests, Institutional, Principal Investigator: Netris Pharma; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Principal Investigator: Pfizer; Financial Interests, Institutional, Principal Investigator: Roche; Non-Financial Interests, Personal, Principal Investigator: ARCAGY-GINECO; Non-Financial Interests, Personal, Advisory Board: French National Cancer Institute ; Non-Financial Interests, Personal, Advisory Board: Unicancer. A. Lortholary: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: Clovid Oncology; Financial Interests, Personal, Other, Congress participation: Novartis; Financial Interests, Personal, Other, Congress participation: Pfizer; Financial Interests, Personal, Other, Congress participation: Roche. B. Asselain: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Daiichi; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Personal, Advisory Board: Pierre Fabre. J. Alexandre: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Institutional, Funding: Janssen; Financial Interests, Institutional, Funding: MSD; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: Agenus; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: GSK. A. Floquet: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Clovis Oncology; Non-Financial Interests, Personal, Member: IMAGYN patient association; Financial Interests, Personal, Other, Congress participation: AstraZeneca; Financial Interests, Personal, Other, Congress participation: MSD; Financial Interests, Personal, Other, Congress participation: GSK; Financial Interests, Personal, Other, Congress participation: Pharma Mar; Financial Interests, Personal, Other, Congress participation: Roche. L. Chardin: Financial Interests, Institutional, Funding: AstraZeneca. N. Delanoy: Financial Interests, Personal, Advisory Board: GSK-Tesaro; Financial Interests, Personal, Invited Speaker: GSK-Tesaro; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: Clovis Oncology. C. Gavoille: Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Institutional, Principal Investigator: Fujirebio. B. You: Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: GSK; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Roche-Genentech; Financial Interests, Personal, Advisory Role: ECS Progastrin; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Clovis Oncology; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: LEK. E. Pujade-Lauraine: Non-Financial Interests, Personal and Institutional, Member of the Board of Directors, Medical Director and CEO: ARCAGY-GINECO; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Roche; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Clovis Oncology; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Genmab. All other authors have declared no conflicts of interest.