Iparomlimab/Tuvonralimab Plus Chemo ± Bevacizumab Yields Responses in Recurrent/Metastatic Cervical Cancer

Cervical Cancer| lertsakwiman – stock.adobe.com

Treatment with the novel bifunctional antibody iparomlimab and tuvonralimab (QL1706) in combination with chemotherapy with or without bevacizumab (Avastin) led to antitumor activity in the first-line treatment of patients with recurrent or metastatic cervical cancer, according to updated data from the phase 2 DUBHE-C-204 trial (NCT05179317).¹

Findings presented at the 2024 ESMO Asia Congress showed that at a median follow-up of 27.0 months (range, 1.4-35.3), 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%), which included 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%, no patients had progressive disease, and 1.7% of patients were not evaluable (NE) for response. The disease control rate (DCR) was 98.3% (95% CI, 90.8%-100%).

In cohort 1 (n = 28), patients treated with iparomlimab/tuvonralimab plus chemotherapy without bevacizumab experienced a confirmed ORR of 75.0% (95% CI, 55.1%-89.3%) and a DCR of 100% (95% CI, 87.7%-100%). The CR, PR, and SD rates were 14.3%, 60.7%, and 25.0%, respectively.

Patients in cohort 2 (n = 30) treated with iparomlimab/tuvonralimab plus chemotherapy and bevacizumab 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%). The respective CR, PR, and SD rates were 10.0%, 66.7%, and 20.0%. One patient (3.3%) was not evaluable for response.

“[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,” presenting study author Danbo Wang, MD, PhD, of the Department of Gynecology at the Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital and Institute, in Shenyang, China, said in a presentation of the data.

Background for Iparomlimab/Tuvonralimab and DUBHE-C-204 Design

Iparomlimab/tuvonralimab is a bifunctional MabPair^® product consisting of an anti–PD-1 IgG4 antibody and an anti–CTLA-4 IgG1 antibody.

The open-label, nonrandomized, multicenter DUBHE-C-204 trial enrolled patients with recurrent or metastatic cervical cancer that was not amenable to curative treatment. No prior systemic chemotherapy was allowed; however, prior radiotherapy and chemotherapy were permitted. Patients needed to have an ECOG performance status of 0 or 1.

Enrolled patients were assigned to cohort 1 or cohort 2. Those in cohort 1 received iparomlimab/tuvonralimab at 5 mg/kg once every 3 weeks in combination with chemotherapy. Patients in cohort 2 received iparomlimab/tuvonralimab at 5 mg/kg once every 3 weeks in combination with chemotherapy and bevacizumab.

In both arms, iparomlimab/tuvonralimab was given until disease progression, unacceptable toxicity, or withdrawal of consent. The chemotherapy regimens in both groups lasted for 6 total cycles, and treatment comprised paclitaxel at 175 mg/m² or 135 mg/m² once every 3 weeks plus cisplatin at 50 mg/m² or carboplatin at area under the curve 5 once every 3 weeks.

Safety served as the trial’s primary end point. Secondary end points included ORR, duration of response, DCR, progression-free survival (PFS) per RECIST 1.1 criteria, and overall survival (OS).

Among all enrolled patients in both cohorts (n = 60), the median age was 52.0 years (range, 31-75), and most had an ECOG performance status of 1 (58.3%). Disease stage at initial diagnosis included stage I (11.7%), stage II (21.7%), stage IIIB (15.0%), stage IIIC (23.3%), stage IVA (1.7%), and stage IVB (13.3%). Histological subtypes comprised adenocarcinoma (16.7%), adenosquamous carcinoma (5.0%), and squamous cell carcinoma (78.3%). Most patients (86.7%) had recurrent disease at the time of enrollment. Patients had a PD-L1 CPS of less than 1 (28.3%); at least 1 and less than 10 (26.7%); or at least 10 (38.3%).

Notably. 11.7% of patients received surgery as their only prior treatment; 40% underwent prior chemoradiation or radiation alone; 46.7% received surgery along with prior chemoradiation or radiation; and 3.3% received no prior treatment.

Additional Efficacy and Safety Data

Findings also showed that evaluable patients in the overall population (n = 58) experienced a median PFS of 15.1 months (95% CI, 9.2-20.2). The median PFS was 14.3 months (95% CI, 7.1-24.1) in cohort 1 (n = 28) and 16.4 months (95% CI, 7.4-NE) in cohort 2 (n = 30).

OS data were immature at the June 25, 2024, data cutoff. The median OS was not reached (NR; 95% CI, 21.9-NE) in the overall population, NR (95% CI, 21.1-NE) in cohort 1, and NR (95% CI, 14.7-NE) in cohort 2. The 12-month OS rates were 83.9% (95% CI, 71.4%-91.3%), 88.9% (95% CI, 69.4%-96.3%), and 79.3% (95% CI, 59.6%-90.1%) in the overall population, cohort 1, and cohort 2, respectively. The respective 24-month OS rates were 60.7% (95% CI, 46.7%-72.1%), 66.7% (95% CI, 45.7%-81.1%), and 55.2% (95% CI, 35.6%-71.0%).

A subgroup analysis showed that survival benefits were observed irrespective of PD-L1 CPS status, Wang explained. In patients with a PD-L1 CPS of less than 1 (n = 17), a CPS of at least 1 (n = 37), and a CPS of at least 10 (n = 21), the median PFS was NE (95% CI, 9.5-NE), 12.5 months (95% CI, 6.7-17.9), and 17.3 months (95% CI, 6.0-NE), respectively.

The median OS was NR in all 3 PD-L1 CPS subgroups. For those with a PD-L1 CPS of less than 1, the 12- and 24-month OS rates were 82.4% (95% CI, 54.7%-93.9%) and 70.6% (95% CI, 43.1%-86.6%), respectively. The OS rates were 85.7% (95% CI, 69.0%-93.8%) at 12 months and 54.3% (95% CI, 36.6%-69.0%) at 24 months in the subgroup of patients with a PD-L1 CPS of at least 1. The respective 12- and 24-month OS rates were 94.7% (95% CI, 68.1%-99.2%) and 68.4% (95% CI, 42.8%-84.4%) in the subgroup of patients with a PD-L1 CPS of at least 10.

Regarding safety in the overall population (n = 60), all patients experienced any-grade treatment-emergent adverse effects (TEAEs) and any-grade treatment-related AEs (TRAEs). Grade 3 or higher TEAEs and grade 3 or higher TRAEs were reported in 80.0% and 75.0% of patients, respectively. The rate of any-grade and grade 3 or higher serious TRAEs were 36.7% and 33.3%, respectively. TRAEs led to treatment discontinuation in 31.7% of patients. One patient (1.7%) died due to a TRAE; however, the cause of this death was unknown and possibly related to bevacizumab.

The most common TRAEs reported in at least 20% of the overall population included decreased white blood cell count (grade 1/2, 40%; grade ≥3, 33.3%), decreased neutrophil count (21.7%; 38.3%), anemia (36.7%; 11.7%), decreased platelet count (26.7%; 11.7%), hypothyroidism (33.3%; 0%), alopecia (33.3%; 0%), decreased lymphocyte count (10%; 18.3%), nausea (23.3%; 3.3%), decreased weight (25%; 0%), myelosuppression (11.7%; 10%), rash (20%; 1.7%), hyperthyroidism (21.7%; 0%), and vomiting (18.3%; 1.7%).

Immune-related AEs that were reported in at least 2 patients in the overall population included hypothyroidism (grade 1/2, 28.3%; grade ≥3, 0%), hyperthyroidism (13.3%; 0%), rash (11.7%; 0%), myocardial injury (6.7%; 1.7%), increased amylase levels (5%; 0%), anemia (1.7%; 1.7%), renal injury (1.7%; 1.7%), immune-mediated hyperthyroidism (3.3%; 0%), immune-mediated dermatitis (3.3%; 0%), allergic dermatitis (3.3%; 0%), increased alpha hydroxybutyrate dehydrogenase level (3.3%; 0%), increased cortisol level (3.3%; 0%), increased blood corticotrophin level (3.3%; 0%), diarrhea (3.3%; 0%), and myelosuppression (3.3%; 0%).

An ongoing phase 3 trial (NCT05446883) is further evaluating iparomlimab/tuvonralimab in combination with chemotherapy with or without bevacizumab in the first-line treatment of patients with persistent, recurrent, or metastatic cervical cancer. In the double-blind study being conducted in China, investigators are randomly assigning patients to receive iparomlimab/tuvonralimab plus chemotherapy with or without bevacizumab; or placebo plus chemotherapy with or without bevacizumab.²

Disclosures: Dr Wang did not declare any financial interests.

References

1. Liu N, Yang Z, Tang D, et al. First-line iparomlimab and tuvonralimab (QL1706) + chemotherapy (chemo) ± bevacizumab (BEV) for recurrent or metastatic cervical cancer (r/mCC): updated results of the phase II DUBHE-C-204 study. Ann Oncol. 2024;35(suppl 4):S1544. doi:10.1016/j.annonc.2024.10.394
2. QL1706 plus chemotherapy±bevacizumab for the first-line treatment of persistent, recurrent or metastatic cervical cancer. ClinicalTrials.gov. Updated November 30, 2022. Accessed January 2, 2025. https://clinicaltrials.gov/study/NCT05446883