Updated findings from the phase 2 DUBHE-C-204 trial indicate that the combination of iparomlimab and tuvonralimab (QL1706) with chemotherapy, with or without bevacizumab, demonstrates promising antitumor activity in the first-line treatment of patients with recurrent or metastatic cervical cancer. The data, presented at the 2024 ESMO Asia Congress, highlight a significant objective response rate and disease control rate, suggesting a potential new treatment option for this patient population.
Efficacy Results
The trial's overall efficacy-evaluable population (n = 58) experienced a confirmed objective response rate (ORR) of 75.9% (95% CI, 62.8%-86.1%), including a complete response (CR) rate of 12.1% and a partial response (PR) rate of 63.8%. The stable disease (SD) rate was 22.4%, and the disease control rate (DCR) reached 98.3% (95% CI, 90.8%-100%). Median progression-free survival (PFS) was 15.1 months (95% CI, 9.2-20.2).
In cohort 1 (iparomlimab/tuvonralimab plus chemotherapy without bevacizumab, n = 28), the confirmed ORR was 75.0% (95% CI, 55.1%-89.3%), and the DCR was 100% (95% CI, 87.7%-100%). Cohort 2 (iparomlimab/tuvonralimab plus chemotherapy and bevacizumab, n = 30) achieved a confirmed ORR of 76.7% (95% CI, 57.7%-90.1%) and a DCR of 96.7% (95% CI, 82.8%-99.9%).
"[Iparomlimab/tuvonralimab] combined with cisplatin or carboplatin [and] paclitaxel with or without bevacizumab showed promising antitumor activity as first-line treatment in recurrent/metastatic cervical cancer, regardless of [PD-L1] combined positive score [CPS] status," said Dr. Danbo Wang, from the Cancer Hospital of Dalian University of Technology.
Study Design and Patient Characteristics
The open-label, nonrandomized, multicenter DUBHE-C-204 trial enrolled patients with recurrent or metastatic cervical cancer who had not received prior systemic chemotherapy. Patients were assigned to either cohort 1 (iparomlimab/tuvonralimab plus chemotherapy) or cohort 2 (iparomlimab/tuvonralimab plus chemotherapy and bevacizumab). Iparomlimab/tuvonralimab was administered at 5 mg/kg once every 3 weeks until disease progression or unacceptable toxicity. Chemotherapy regimens included paclitaxel plus cisplatin or carboplatin for 6 cycles.
The primary endpoint of the trial was safety, while secondary endpoints included ORR, duration of response, DCR, PFS, and overall survival (OS).
Survival Analysis and PD-L1 Status
Overall survival (OS) data were immature at the data cutoff. However, subgroup analysis indicated survival benefits irrespective of PD-L1 CPS status. The 12-month OS rates were 83.9% in the overall population, 88.9% in cohort 1, and 79.3% in cohort 2. The 24-month OS rates were 60.7%, 66.7%, and 55.2%, respectively.
Safety Profile
All patients experienced any-grade treatment-emergent adverse effects (TEAEs), with grade 3 or higher TEAEs reported in 80.0% of patients. The most common TRAEs included decreased white blood cell count, decreased neutrophil count, and anemia. TRAEs led to treatment discontinuation in 31.7% of patients. One patient (1.7%) died due to a TRAE, potentially related to bevacizumab.
Ongoing Phase 3 Trial
A phase 3 trial (NCT05446883) is currently underway to further evaluate iparomlimab/tuvonralimab in combination with chemotherapy with or without bevacizumab as a first-line treatment for patients with persistent, recurrent, or metastatic cervical cancer. This double-blind study in China is randomizing patients to receive either the iparomlimab/tuvonralimab combination or placebo, along with chemotherapy with or without bevacizumab.
