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).
Authors: Kang Hyunseok , Ahn Myung-Ju , Muzaffar Jameel , Keam Bhumsuk , Bowles Daniel W. , Wong Deborah J.L. , Ho Alan Loh , Kim Sung-Bae , Worden Francis P. , Yun Tak , Sari Suha , Conlan Maureen G , Hanna Glenn J. 
Published: October 2024

6020

Background:
ACC is a rare tumor that overexpresses VEGF, primarily affecting salivary glands. Often indolent, it can progress, with metastases common in lungs, liver, and bone. There are no FDA-approved systemic treatments (tx) for R/M ACC. Rivoceranib is an oral tyrosine kinase inhibitor (TKI) that potently and selectively inhibits VEGFR2.
Methods:
In this single-arm, open-label trial, patients (pts) with R/M ACC with evidence of ≥20% progression by RECIST v1.1 or new lesions within the preceding 6 mo were eligible; there was no limit on prior tx. Pts received rivoceranib 700 mg once daily until progression or withdrawal with pre-planned dose reductions for toxicity. Primary endpoint was objective response rate (ORR) per RECIST v1.1 by investigator (PI) and by Independent Review Committee (IRC). Secondary endpoints included duration of response (DoR), progression-free survival (PFS), time to progression (TTP), overall survival, and safety. Exploratory analysis included disease control rate (DCR), and ORR using CHOI criteria by IRC.
Results:
80 pts (72 evaluable) were enrolled at 11 sites in the US and Korea (53% male; median age: 55 yr). Primary tumor sites: major (34%) and minor (59%) salivary glands and other (8%). 5 (6%) pts had locoregional disease only and 74 (93%) had metastatic disease. Most had prior surgery (89%) and radiation (96%); 53% had prior systemic tx (44% chemotherapy; 18% VEGFR TKI). Median follow-up was 15 mo (2–19); 20 pts remain on tx. PI-assessed efficacy data are listed in the table. ORR in pts with or without prior systemic tx was 13.9% and 16.9%, respectively. ORR by CHOI was 50.8% overall (51% VEGFR TKI-naive and 50% VEGFR TKI treated). 18% of pts discontinued tx, 74% had at least 1 dose reduction, and 93% dose interruption for adverse events (AEs). All pts had ≥1 AE and 80% had Grade ≥3 AEs, including 3 Grade 5 AEs (2 epistaxis [1 related], 1 acute respiratory failure). Common ( > 30%) AEs were hypertension (65%), fatigue (61%), nausea and headache (50%), stomatitis (46%), diarrhea (40%), decreased appetite (38%), proteinuria (36%) and palmar-plantar erythrodysesthesia syndrome (34%). Grade ≥3 AEs in ≥5% of pts were hypertension (43%), stomatitis (8%), fatigue and anemia (6%), and back pain and pneumothorax (5%).
Conclusions:
In this population of R/M ACC with unmet medical need, rivoceranib showed promising antitumor activity, particularly among VEGFR TKI-naïve pts. The safety profile was consistent with other VEGFR TKIs.
Clinical trial information: NCT04119453.

Total(N = 72)
VEGFR TKI-Naïve(n = 59)
VEGFR TKI Prior Tx(n = 13)

ORR* (%)95% CI
10 (13.9)6.9-24.1
10 (16.9)8.4-29.0
0

Median (m) DOR (mo)
12.0
12.0
-

6, 9, 12 mo DOR (%)
100, 88.9, 59.3
100, 88.9, 59.3
-

DCR (%)95% CI
43 (59.7)47.5-71.1
33 (55.9)42.4-68.8
10 (76.9)46.2-95.0

mTTP (mo)
10.9
9.0
16.4

mPFS (mo)
9.0
9.0
9.1

6, 9, 12 mo PFS rate (%)
76.7, 53.2, 43.0
74.9, 51.1, 41.3
84.6, 61.7, 49.4

*All partial responses.