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

The phase 2 CC-ANNIE trial was launched in China investigating anlotinib plus sintilimiab for recurrent platinum-resistant ovarian clear cell carcinoma.

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