Phase Ib INEOV neoadjuvant trial of durvalumab +/- tremelimumab with platinum chemotherapy for patients (pts) with unresectable ovarian cancer (OC): Final complete resection and pathological response rates.

person Alexandra Leary Medical Gynecology, Gustave Roussy, Villejuif, France info_outline Alexandra Leary, Thibault De La Motte Rouge, Alain Lortholary, Bernard Asselain, Jerome Alexandre, Anne Floquet, Aude Marie Savoye, Nicolas Delanoy, Céline Gavoille, Benoit You, Veronique D'hondt, Julien Grenier, Catherine Genestie, Laure Chardin, Eric Pujade-Lauraine

Authors person Alexandra Leary Medical Gynecology, Gustave Roussy, Villejuif, France info_outline Alexandra Leary, Thibault De La Motte Rouge, Alain Lortholary, Bernard Asselain, Jerome Alexandre, Anne Floquet, Aude Marie Savoye, Nicolas Delanoy, Céline Gavoille, Benoit You, Veronique D'hondt, Julien Grenier, Catherine Genestie, Laure Chardin, Eric Pujade-Lauraine Organizations Medical Gynecology, Gustave Roussy, Villejuif, France, Centre Eugène-Marquis, Rennes, France, Hôpital Privé du Confluent, Nantes, France, ARCAGY-GINECO, Paris, France, Medical Oncology Department, Hôpital Cochin, AP-HP, Paris, France, Oncology, Institut Bergonié, Bordeaux, France, Institut Jean Godinot, Reims, France, Medical Oncology Department, Hôpital Européen Georges Pompidou, AP-HP, Paris, France, ICL- Alexis Vautrin Center, Vandoeuvre Les Nancy, France, Medical Oncology Department, HCL-Hôpital Lyon Sud, Pierre Benite, France, Institut Régional du Cancer de Montpellier, Montpellier, France, Institut du Cancer Avignon Provence, Avignon, France, INSERM U981, Gustave Roussy, Villejuif, France, Gustave Roussy, INSERM U981, Villejuif, France Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: We have shown that neoadjuvant carboplatin and paclitaxel (NACP) increased tumor infiltrating lymphocytes and PDL1 expression in OC pts. INEOV evaluated NACP with durvalumab (D) +/- tremelimumab (T) in pts with unresectable OC. We previously reported that NACP with D+/-T was feasible and safe but the addition of T did not improve interval debulking surgery (IDS) rates after 3 cycles (C3) (ESMO 2021). Here we provide an update with longer follow up including data on delayed IDS performed after 6 cycles of neoadjuvant treatment. Key secondary endpoints include complete resection (CC0) and complete pathological response rates. Methods: Pts with stage IIIC/IV OC were randomized to NACP + D (1125mg) alone (arm A) or with T (75mg once at C2) (arm B). Interval debulking surgery (IDS) was planned after C3, or delayed after C6. Pts in arm A not operable after C3 crossed over to arm B, pts in arm B crossed over to standard of care (SOC). Pts were assessed for delayed IDS after C6. Complete pathological response (pCR) was defined as no residual tumor cells found on any surgical specimens, or no residual tumor cells on any samples outside the ovary at IDS. Results: Sixty four (N = 64) of 66 pts (IIIC/IV: 70%/30%) randomized were evaluable. After C3, 66% (21/32) of pts in arm A and 59% (19/32) in arm B had IDS. The 11 pts in arm A not candidate for IDS after C3 crossed over to arm B until C6 and 5/11 benefited from delayed IDS. The 13 pts in arm B inoperable at C3 went on to receive SOC (NACP +/- bevacizumab), and 5/13 became eligible for delayed IDS after C6. Overall, IDS was performed in 50 of 64 evaluable pts, and most (45/50) achieved macroscopically complete resection (CC0), so that the overall CC0 rate was 70% (45/64), with no significant difference between arms (CC0 = 75% vs 65% in arm A vs B). Among the 50 pts who had IDS, complete pathological responses were observed in 18% of pts. Conclusions: Taking into account the whole treatment strategy including delayed IDS after 6 cycles of neoadjuvant treatment, we have shown that neoadjuvant CP with D+/- T results in encouraging CC0 (70%) and pCR (18%) rates. However there was no apparent benefit to the addition of T to D. Studies are ongoing to describe the immune features predictive of pCR as well as the impact of treatment on the immune microenvironment. Clinical trial information: NCT03249142.