‘Amazing’ Results With Drug Combo in Metastatic Cervical Cancer

SAN JUAN, Puerto Rico — The investigational antibody-drug conjugate sacituzumab tirumotecan plus pembrolizumab (Keytruda) demonstrated encouraging antitumor activity in patients with recurrent or metastatic cervical cancer, according to phase II data.

With a median follow-up of 24.7 months among 68 patients, the objective response rate (ORR) with the combination was 51% (with a confirmed ORR of 40%), and the complete response rate was 6%, reported Xiaohua Wu, MD, PhD, of Fudan University Shanghai Cancer Center, at the Society of Gynecologic Oncology (SGO) annual meeting.

There were no new safety signals, and the safety profile was consistent with what has been observed for each drug.

The median duration of response was not reached among all patients who achieved a confirmed response, with eight patents having an ongoing response of more than 20 months. Median progression-free survival was 7.3 months, while median overall survival (OS) was 18.9 months.

SGO invited discussant Ritu Salani, MD, MBA, of the University of California Los Angeles, described the ORR and OS results as “amazing,” suggesting that they compare favorably to those seen with tisotumab vedotin (Tivdak), the current standard of care in this setting. In a phase III trial, patients who received tisotumab vedotin in the second or third line of therapy had a median OS of 11.5 months and an ORR of 17.8%, with six complete responses.

Sacituzumab tirumotecan is a TROP2-directed antibody-drug conjugate that targets advanced solid tumors such as non-small cell lung cancer, breast cancer, and gastric cancer, as well as gynecologic tumors. TROP2 is associated with poorer outcomes.

In a previous phase I/II study of patients with previously treated cervical cancer, sacituzumab tirumotecan monotherapy had promising activity.

For this study, the researchers hypothesized that the combination of sacituzumab tirumotecan and pembrolizumab “may enhance antitumor activity and clinical benefit due to their complementary mechanisms of action.”

These results were from cohort A of the study which included women with histologically or cytologically confirmed recurrent or metastatic cervical cancer, with disease progression during or after treatment with platinum-based doublet chemotherapy, who had received one or two prior systemic therapy regimens.

The 68 patients (median age 52 years) were assigned to receive sacituzumab tirumotecan at doses of 3 mg/kg (3 patients), 4 mg/kg (30 patients), or 5 mg/kg (35 patients) plus pembrolizumab. Overall, 88% of patients had recurrent and metastatic cervical cancer, and the remainder had recurrent disease.

The study population was evenly split between those who had received one or two prior lines of therapy, and 51% who had received prior immunotherapy.

The confirmed ORRs in the 3-mg, 4-mg, and 5-mg groups were 67%, 27%, and 49%. Among the patients who received prior immunotherapy, the ORR was 54% (including confirmed and unconfirmed responses).

Treatment-related adverse events (TRAEs) were observed in all patients, with grade 3 or 4 TRAEs reported in 57%. The most common grade 3 or 4 TRAEs were anemia, decreased neutrophil count, and decreased white blood cell count. One patient had grade 2 interstitial lung disease. There were no cases of febrile neutropenia.

Serious TRAEs were observed in 21% of patients, with 38% leading to dose reduction, 54% leading to dose interruption, and 3% leading to treatment discontinuation. No TRAEs resulted in deaths.

Salani noted that phase II studies in recurrent cervical cancer — “where we continue to struggle to have good objective response rates and progression-free survival” — are ongoing. “We saw such impressive data with [sacituzumab tirumotecan] and pembrolizumab, and we hope to capitalize on this, and see this in phase III studies,” she added.

She said that a phase III trial will evaluate sacituzumab tirumotecan versus physician’s choice of treatment (including tisotumab vedotin) as second-line therapy for recurrent or metastatic cervical cancer, while Wu noted that another phase III study will investigate sacituzumab tirumotecan plus pembrolizumab with or without bevacizumab (Avastin) as first-line maintenance therapy in participants with cervical cancer.