756P - Final analysis of KGOG3046/TRU-D: A phase II study of durvalumab and tremelimumab with front-line neoadjuvant chemotherapy in patients with advanced-stage ovarian cancer

Background

In the original cohort (O) of KGOG 3046 study (NCT03899610) on newly diagnosed advanced-stage epithelial ovarian cancer (aEOC), patients receiving neoadjuvant chemotherapy (NAC) with durvalumab [D] and multiple low dose of tremelimumab [T] exhibited promising long-term survival outcomes. After completing enrollment of the original cohort, an expansion cohort (E) was initiated with a regimen of NAC with D and the single high dose of T. Here, we reported final long-term survival results from the KGOG 3046 study.

Methods

This open-label, investigator-initiated study enrolled patients with FIGO stage IIIC-IV EOC. Enrolled patients received the following neoadjuvant therapy (paclitaxel + carboplatin [3 cycles] + D 1,500 mg q3w + T (75mg q3w for O; 300 mg [1 cycle] for E). After NAC, all patients underwent interval debulking surgery (IDS), and three cycles of D (1,120 mg) and adjuvant chemotherapy followed by D maintenance (1,120 mg [total 12 cycles]). The primary endpoint was the 12-month PFS rate, and secondary endpoints were the pathologic complete response (pCR), overall survival, and safety.

Results

Between June 2019 and July 2021, 45 patients were enrolled (O, n=23; E, n=22); the median follow-up was 30.9 (95% CI: 9.7–42.2) months. The majority of the patients presented high-grade serous carcinoma (91.1%) and stage IV (77.8%) disease. After NAC, 5 (11.1%) had a pCR (17.4 in O vs. 4.6% in E). The 12-month, 24-month, and 30-month PFS rates were 65.9% (63.6% in O and 68.2% in E), 40.5% (45.0% in O and 36.4% in E), and 38.1% (40.0% in O and 36.4% in E), respectively. The 30-month OS rate was 87.7% (89.1 vs. 85.9%). Adverse events were manageable, with grade ≥ 3 skin rash (17.8%). In exploratory analysis, patients with high TIL and PD-L1 expression showed better survival outcomes.

Conclusions

This study showed durable responses in approximately 40% of aEOC patients without maintenance therapy, supporting the potential benefit of NAC with D+T in aEOC.

Clinical trial identification

NCT03899610.

Editorial acknowledgement

Legal entity responsible for the study

Jung-Yun Lee.

Funding

AstraZeneca.

Disclosure

J. Kim: Financial Interests, Personal, Advisory Board: Takeda Korea, GSK Korea, Boryung, Vifor Pharma, MSD Korea, LG Pharma; Financial Interests, Personal, Invited Speaker: CMIC, AstraZeneca, Janssen. J. Lee: Financial Interests, Personal, Advisory Board, DP-02: AstraZeneca; Financial Interests, Personal, Advisory Board, FLORA-5: CanariaBio; Financial Interests, Personal, Advisory Board, GEN1046-05: Genmab; Financial Interests, Personal, Advisory Board, GI-101: GII; Financial Interests, Personal, Advisory Board, MIRASOL: ImmunoGen; Financial Interests, Personal, Advisory Board, MK4830-002: MSD; Financial Interests, Personal, Advisory Board, SGNTV-03: Seagen; Financial Interests, Institutional, Local PI: Advenchen, Ascendis Pharma, Alkermes, AstraZeneca, BeiGene, BergenBio, BMS, CanariaBio, Cellid, Clovis Oncology, Eisai, Genmab, Genemedicine, GII, GSK, ImmunoGen, Janssen, Merck, Mersana, MSD, Novartis, Onconic Therapeutics, ONO; Financial Interests, Personal, Invited Speaker: AstraZeneca, Eisai. All other authors have declared no conflicts of interest.