Suvemcitug Plus Chemo Boost PFS in Platinum-Resistant Ovarian Cancer

Treatment with suvemcitug plus chemotherapy led to a clinically meaningful and statistically significant improvement in progression-free survival (PFS) compared with placebo plus chemotherapy in patients with platinum-resistant ovarian cancer, regardless of prior treatment with antiangiogenic agents or PARP inhibitors, meeting the primary end point of the phase 3 SCORES trial (NCT04908787).

Data presented at the 2024 ASCO Annual Meeting showed that at a median follow-up was 14.36 months for the suvemcitug group (n = 281) and 14.26 months for the placebo group (n = 140), the median PFS was 5.49 months (95% CI, 4.93-5.95) and 2.73 (95% CI, 1.94-3.75) in the suvemcitug vs placebo groups, respectively (stratified HR, 0.46; 95% CI, 0.35-0.60; P < .0001; unstratified HR, 0.53; 95% CI, 0.42-0.67).

“Suvemcitug plus chemotherapy showed a statistically significant and clinically meaningful PFS improvement across all predefined subgroups compared [with] chemotherapy alone,” lead study author Guangwen Yuan, MD, said during a presentation of the data. “Suvemcitug plus chemotherapy also improved overall response rate [ORR], disease control rate [DCR], and duration of response [DOR].”

Yuan works in the Gynecologic Oncology Department of the National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, and the Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, China.

The recombinant humanized anti-VEGF rabbit monoclonal antibody suvemcitug previously demonstrated efficacy and a favorable safety profile in combination with chemotherapy in patients with platinum-resistant ovarian cancer during a phase 1b study (CTR20171512).

The randomized, double-blind, multicenter SCORES trial enrolled patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer whose disease progressed on or after platinum-based chemotherapy; who received 1 or fewer lines of systemic therapy for ovarian cancer after platinum resistance; and who had an ECOG performance status of 0 or 1.

Eligible patients were randomly assigned 2:1 to either the experimental or control arm. Patients on the experimental arm were treated with suvemcitug at 1.5mg/kg once every 2 weeks with chemotherapy; patients on the control arm received placebo plus chemotherapy. Chemotherapy options in both arms consisted of paclitaxel, pegylated liposomal doxorubicin, or topotecan.

Patients were stratified by number of prior systemic therapies (1 vs 2), chemotherapy regimen (paclitaxel vs pegylated liposomal doxorubicin vs topotecan), prior anti-angiogenic therapy (yes vs no), and platinum-refractory status (yes vs no).

The primary end point was PFS as assessed by blinded independent central review (BICR) per RECIST 1.1 criteria, key secondary end points included overall survival (OS), and other secondary end points included PFS assessed by investigators, ORR, DCR, DOR, adverse effects (AEs) and serious AEs, quality of life, and pharmacokinetics.

Patients enrolled on the study had a median age of 56.0 years (range, 36-76) and 55.0 years (range, 34-79) in the experimental and control arms, respectively. Furthermore, patients had an ECOG performance score of 0 (experimental arm, 37.7%; control arm, 28.6%) or 1 (62.3%; 71.4%); tumor histologic types of high-grade serous adenocarcinoma (98.9%; 97.1%) or endometrioid carcinoma (1.1%; 2.9%); and were treated with 1 (31.3%; 28.6%), 2 (37.4%; 37.1%), 3 (21.4%; 25.0%), or 4 or more (10%; 9.3%) previous lines of antitumor therapy.

Prior anticancer therapy consisted of chemotherapy (experimental arm, 100%; control arm, 100%), PARP Inhibitors (48.4%; 50%), and antiangiogenic agents (50.2%; 50%), including bevacizumab (Avastin; 43.8%; 43.6%). A minority of patients (9.6%; 10.7%) presented with platinum-refractory ovarian cancer.

"An exploratory analysis for subgroups by age, ECOG performance [status], ascites, number of lines of previous regimens, platinum-free intervals, chemotherapy of investigator's choice, and previous anti-angiogenic therapy [showed that] suvemcitug [demonstrated] consistent PFS benefits across all predefined subgroups," Yuan explained.

Additional data showed that the ORR was 26.0% in the experimental arm vs 12.1% in the control arm per BICR assessment. Tumor reduction was observed in 64.4% and 35.7% of patients, respectively. No patients in the experimental arm achieved a complete response (CR) compared with 1 patient (0.7%) in the control arm. The stable disease (SD) rate was 50.5% for the suvemcitug arm vs 37.1% for the placebo arm, and the respective DCRs were 76.5% and 49.3%. The respective median DORs were 8.80 months (95% CI, 6.11-10.94) and 6.05 months (95% CI, 4.21–not evaluable).

Per investigator assessment, suvemcitug plus chemotherapy led to improvement in CR rate (experimental arm, 1.4%; control arm, 0.7%), partial response rate (21.7%; 7.9%), SD rate (52.0%; 38.6%), ORR (23.1%; 8.6%), DCR (75.1%; 47.1%), and DOR (7.23 months; 5.52 months). Regarding investigator-assessed PFS in these groups, the median PFS was 5.39 months (95% CI, 4.80-5.59) vs 2.46 (95% CI, 1.94-3.65), respectively (stratified HR, 0.47; 95% CI, 0.37-0.61); P < .0001).

The median OS was 16.07 months (95% CI, 13.67-18.53) for the suvemcitug arm vs 14.88 months (95% CI, 11.43-18.73) for the placebo arm (stratified HR, 0.79; 95% CI, 0.58-1.07; P = .1244). The respective 12-month OS rates were 65.0% (95% CI, 58.4%-70.8%) and 54.2% (95% CI, 44.5%-62.9%). The 24-month OS rates were 35.7% (95% CI, 26.5%-44.9%) vs 22.5% (95% CI, 11.4%-35.9%), respectively.

“[Although] the OS data are immature, a trend of OS benefit is observed in the suvemcitug plus chemotherapy arm,” Yuan said.

Reference

Yuan G, Wu L, Li Q, et al. A phase III randomized, double-blinded, placebo-controlled study of suvemcitug combined with chemotherapy for platinum-resistant ovarian cancer (SCORES). J Clin Oncol. 2024;42(suppl 16):LBA5516. doi:10.1200/JCO.2024.42.17_suppl.LBA5516