Phase 2 Trial Launched of Anlotinib Plus Sintilimab in China for OCCC

A recentlay launched phase 2 CC-ANNIE trial (NCT05130515) in China will utilize anlotinib (AL3818) plus sintilimab (Tyvyt) for women with recurrent platinum-resistant ovarian clear cell carcinoma (OCCC), according to a presentation by Bingzhong Zhang, MD, at The Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.¹

Adult women up to age 70 with histologically confirmed platinum-resistant recurrent OCCC are eligible. Patients are required to have received at least 1 prior platinum-containing treatment regimen within the previous 6 months and to have an ECOG score of 0 or 1. All patients must have at least 1 measurable lesion according to RECIST 1.1 criteria.

Enrollees will receive 200 mg niraparib once daily plus 10 mg anlotinib on days 1 to 14 of each 21-day cycle until disease progression or intolerable toxicity. Investigators hope to enroll 20 patients into the trial at Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University in Canton, China.

The primary end point is objective response rate (ORR). Secondary end points include progression-free survival (PFS) and overall survival, duration of response (DOR), and safety. Investigators expect to complete the study by the end of 2023.

Platinum-resistant ovarian cancer is characterized by its poor prognosis and limited treatment options. OCCC is a rare, aggressive form of the disease, accounting for approximately 10% of epithelial ovarian cancers.²OCCC displays greater resistance to cisplatin-based chemotherapy, leading to poor prognosis.³ There is a clear unmet need for this patient population, but few treatment options.

Incidence of OCCC is more common in Korea (10.3%), Taiwan (18.6%), and Japan (15%–25%) compared with 1% to 12% in North America and Europe. The reasons for these differences in incidence are not clear, although investigators have observed molecular differences between tumors arising in different populations.²

This ongoing single arm, single-center study is a follow-up to the phase 2 ANNIE study (NCT04376073). In the previous trial, patients (N = 40) with platinum-resistant, recurrent ovarian epithelial, fallopian tube, or primary peritoneal cancer received 200 mg or 300 mg daily oral niraparib plus 12 mg anlotinib on days 1 to 14 of each 21-day cycle until disease progression or intolerable toxicity. The primary objective was ORR according to RECIST v1.1.

Twenty-five patients underwent imaging evaluation. The ORR was 48.0% (95% CI, 27.0%̃-69.0%) with 12 partial responses and 12 patients with stable disease. The median DOR and median PFS were not reached. Investigators observed drug-related grade 3 or worse treatment-emergent adverse events in 39.4% patients.⁴

In February, investigators at China’s Fujian Medical University Cancer Hospital published findings from a prospective phase 2 trial showing that anlotinib plus sintilimab appeared to be efficacious and safe when used as a second- or later-line treatment in patients with PD-L1–positive, recurrent or metastatic cervical cancer.⁵

Among 42 patients in the intent-to-treat population, the confirmed ORR was 54.8% (95% CI, 38.7%-70.2%). Two patients (4.8%) experienced a complete response (CR), 50% had a partial response, and 33.3% had stable disease. The median time to response was 1.7 months (95% CI, 1.4-2.8).

Thirty-nine patients evaluable for efficacy had a confirmed ORR of 59.0% (95% CI, 42.1%-74.4%) with the combination, which included a CR rate of 5.1%.

Anlotinib is indicated in China for third-line treatment of patients with refractory, advanced non-small cell lung cancer (NSCLC). In February 2022, the FDA’s Oncologic Drug Advisory Committee rejected a biologics license application for use of sintilimab (Tyvyt) injection in combination with pemetrexed and platinum chemotherapy for the first-line treatment of patients with nonsquamous NSCLC.⁶

References

1. Zhang B, Lin, Peng Y, Li J. Anlotinib combined with niraparib dual therapy in platinum-resistant recurrent ovarian clear cell carcinoma ( CC-ANNIE): a single-center, single-arm, phase II trial. Presented at: 2022 SGO Annual Meeting on Women’s Cancer. Phoenix, Arizona; March 28-21, 2022. Poster 586.

2. Iida Y, Okamoto A, Hollis RL, Gourley C, Herrington CS. Clear cell carcinoma of the ovary: a clinical and molecular perspective. Int J Gynecol Cancer. 2021;31(4):605-616. doi: 10.1136/ijgc-2020-001656

3. Wong OGW, Li J, Cheung ANY. Targeting DNA damage response pathway in ovarian clear cell carcinoma. Front Oncol. 2021;11:666815. doi: 10.3389/fonc.2021.666815

4. Liu G, Liu J, Xian B, et al. Preliminary results of anlotinib and niraparib dual therapy evaluation in platinum-resistant recurrent ovarian cancer. J Clin Oncol. 2021;39(suppl 15):e17532. doi: 10.1200/JCO.2021.39.15_suppl.e17532

5. Xu Q, Wang J, Sun Y, et al. Efficacy and safety of sintilimab plus anlotinib for PD-L1–positive recurrent or metastatic cervical cancer: a multicenter, single-arm, prospective phase II trial. J Clin Oncol. Published online February 22, 2022. doi:10.1200/JCO.21.02091

6. Oncologic Drugs Advisory Committee (ODAC) Meeting. FDA website. Accessed March 18, 2022. https://bit.ly/3Bdwluu