Activity of Rivoceranib in Adenoid Cystic Carcinoma Showcased at ASCO 2022

Patients with recurrent or metastatic (R/M) adenoid cystic carcinoma (ACC) treated with the VEGFR2 oral tyrosine kinase inhibitor rivoceranib experienced promising responses and disease control, according to findings from the phase 2 RM-202 study (NCT04119453) presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.

Across 73 efficacy-evaluable patients with R/M ACC in the single-arm, open-label study, objective response rate (ORR) by investigator assessed RECIST 1.1 criteria was 15.1% (95% CI, 7.8%-25.4%) with a disease control rate (DCR) of 64.4% (95% CI, 52.3%-75.3%). By blinded independent review committee (BIRC), the ORR was 9.6% (95% CI, 3.9%-18.8%) and the DCR was 65.8% (95% CI, 53.7%-76.5%). The median duration of response (DOR) was 14.9 months by investigator assessment and 7.2 months by BIRC. After a median follow-up of 19.5 months, the median progression-free survival (PFS) was 9 months (95% CI, 7.5-12.8) per investigator assessment and 9.2 months (95% CI, 8.0-12.9) by BIRC.

“There is no approved standard of care for R/M ACC, so as we investigate rivoceranib’s potential as a treatment option we remain steadfastly focused on the many patients who now have or someday will be diagnosed with this disease,” lead author Hyunseok Kang, MD, medical oncologist at the University of California San Francisco, said in a statement. “The positive results demonstrated in this phase 2 trial of rivoceranib represent a vitally important step forward for them.”

The trial enrolled 80 patients with R/M ACC across 11 sites in the United States and Korea. Fifty-three patients were enrolled at a US site (66.3%). All patients had a documented disease progression within 6 months of entering the study. The target dose of oral rivoceranib was 700 mg daily, with preplanned dose reductions if required. The median age of patients was 54.5 years (range, 28-76) and approximately half had an ECOG performance status of 0 (56.3%) with the remainder having a score of 1. Most patients had a stage IVc tumor (92.5%). The primary tumor locations were the minor salivary gland (58.8%), the major salivary gland (33.8%), and other (7.5%). The sites of metastases were the lung (86.3%), liver (31.3%), bone (25.0%), lymph nodes (25.0%), and pleura (17.5%).

Most patients had received prior surgery (88.8%) and/or radiotherapy (96.3%) before entering the study and the median number of prior systemic therapy lines was 1 (range, 0-8), with 20% of patients having received 3 or more prior lines of therapy. Prior therapies included a VEGFR inhibitor for 17.5% of patients, which consisted of lenvatinib (Lenvima; 12.5%) or axitinib (Inlyta; 5.0%). Almost half of patients received prior chemotherapy (46.3%).

By investigator assessment in those evaluable for efficacy (n = 72), the change in the sum of target lesions was 20.5 mm (range, 5-180) in the 6 months prior to enrollment in the trial. After treatment with rivoceranib, most tumors shrank, with a change in target sum of lesions of –7 mm (range, –43 to 35) in the 6 months after initiating treatment.

“With every participant exhibiting a recent growing lesion upon entering this phase 2 trial of rivoceranib, these results demonstrate significant clinical effectiveness and rivoceranib’s promise as a potential new treatment for patients with R/M ACC,” Saeho Chong, chief executive officer of Elevar, the company developing the therapy, said in a statement. “Our entire Elevar team is greatly encouraged by these results, and we are fully focused on advancing rivoceranib through the regulatory process.”

In patients who received a prior VEGFR inhibitor (n = 13), the ORR by BIRC was 15.4% (95% CI, 1.9%-45.4%). There were no responses indicated by investigator assessment in this group (95% CI, 0%-24.7%). The DCR was 76.9% (95% CI, 46.2%-95.0%) by investigator assessment and 69.2% (95% CI, 38.6%-90.9%) by BICR, with a median DOR that was not estimable (NE) and 6.3 months, respectively. The median PFS was 10.6 months (95% CI, 7.1-17.7) by investigator assessment and 8.9 months (95% CI, 5.3-12.9) by BIRC. The 12-month PFS rates were 43.0% (95% CI, 13.8%-69.8%) by investigator assessment and 26.0% (95% CI, 4.3%-56.2%) by BICR.

In patients who did not receive a prior VEGFR inhibitor (n = 60), the ORR by investigator assessment was 18.3% (95% CI, 9.5%-30.4%) and it was 8.3% by BIRC (95% CI, 2.8%-18.4%). The DCR in this group by investigator assessment was 61.7% (95% CI, 48.2%-73.9%) and it was 65.0% by BIRC (95% CI, 51.6%-76.9%). The median duration of response was 14.9 months by investigator assessment and 7.9 months by BIRC. The median PFS was 9.0 months by investigator assessment (95% CI, 7.3-12.8) and 9.3 months by BIRC (95% CI, 8.0-13.7). The 12-month PFS rates were 38.7% (95% CI, 25.5%-51.8%) and 40.4% (95% CI, 25.6%-54.6%) by investigator and BIRC assessment, respectively.

By BIRC-assessed CHOI response criteria, the ORR with rivoceranib was 51.7% (95% CI, 38.4%-64.8%) in 60 efficacy evaluable patients. In those untreated with a VEGFR inhibitor (n = 48), the ORR by CHOI was 52.1% (95% CI, 37.2%-66.7%) and in those pretreated with a VEGFR inhibitor (n = 12) it was 50% (95% CI, 21.1%-78.9%).

Across the entire intention-to-treat population (N = 80), the median overall survival (OS) was not yet reached, with 74.5% (95% CI, 62.5%-83.1%) of patients alive at 12 months and 61.7% (95% CI, 48.3%-72.5%) of patients alive at 18 months. The median OS was not reached in the VEGFR inhibitor–naïve arm (n = 66) and was 17.5 months (95 CI, 10.0-NE) for those treated with a prior VEGFR inhibitor (n = 14).

At the time of the analysis, 11 patients continued to receive treatment with rivoceranib (13.8%). Treatment discontinuation was primarily related to disease progression (48.8%) or adverse events (AEs; 20%). The relative dose intensity was 60.1% and the median dose was 421 mg/day. An AE of any grade occurred in all patients treated with rivoceranib, with a grade 3 or greater event seen in 80% of patients. The most common AEs of grade 3 or higher in severity were hypertension, stomatitis, anemia, and fatigue. There were 4 fatal AEs (epistaxis [n = 2] and acute respiratory failure [n = 2]).

Further investigation of rivoceranib to optimize the dosing is warrented, according to the poster. In the United States, rivoceranib is also being explored across other indications, chiefly hepatocellular carcinoma, colorectal cancer, and gastric cancer.

Reference

Kang H, Ahn M-J, Muzaffar J, et al. A phase 2 study of the oral vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor, rivoceranib, for recurrent or metastatic (R/M) adenoid cystic carcinoma (ACC). J Clin Oncol. 2022;40(suppl 16):6020. doi:10.1200/JCO.2022.40.16_suppl.6020