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Socazolimab produced encouraging response rates with an acceptable safety profile in patients with recurrent or metastatic cervical cancer, irrespective of PD-L1 status, according to findings from the dose-expansion portion of a phase 1 trial.
Socazolimab (ZKAB001) produced encouraging response rates with an acceptable safety profile in patients with recurrent or metastatic cervical cancer, irrespective of PD-L1 status, according to findings from the dose-expansion portion of a phase 1 trial (NCT03676959) presented during the 2022 ASCO Annual Meeting.1
The fully human monoclonal antibody, when given at 5 mg/kg, elicited an overall response rate (ORR) of 15.4% (95% CI, 8.7%-24.5%) in all patients enrolled to the dose-expansion study (n = 91). Patients with PD-L1–negative disease (n = 28) experienced an ORR of 17.9% (95% CI, 6.1%-36.9%), and patients with PD-L1–positive disease (n = 54) had an ORR of 16.7% (95% CI, 7.9%-29.3%). The median duration of response (DOR) was not yet evaluable (95% CI, 3.32-14.92).
The disease control rate (DCR) achieved with the agent in all patients was 49.5% (95% CI, 38.8%-60.1%). Moreover, the median progression-free survival (PFS) with socazolimab was 4.44 months (95% CI, 2.37-5.75), and the median overall survival (OS) was 14.72 months (95% CI, 9.59–not evaluable). The 6-month OS rate was 78.6% (95% CI, 68.5%-85.8%); the 12-month rate was 58.2% (95% CI, 45.4%-69.0%).
“Our study demonstrates that socazolimab has remarkable safety and efficacy for the treatment of recurrent or metastatic cervical cancer and effective for PD-L1–negative patients,” lead study author Jusheng An, of Cancer Hospital, Chinese Academy of Medical Sciences, and colleagues, wrote in a poster on the data. “Also, it exhibits a safety profile similar to other anti–PD-1/PD-L1 monoclonal antibodies.”
For patients with recurrent or metastatic cervical cancer, currently available second-line treatments have demonstrated poor efficacy and safety. With the phase 1 dose-escalation and -expansion trial, investigators sought to evaluate socazolimab as an alternative option for this population.
The multicenter, single-arm study enrolled female patients who were at least 18 years of age who had recurrent or metastatic cervical cancer confirmed by histopathology or cytology and measurable disease per RECIST v1.1 criteria.2 Patients were required to have failed or have been intolerant to first-line treatment with platinum-based chemotherapy. Other eligibility criteria included having an ECOG performance status of 0 or 1, as well as acceptable blood, organ, and renal function.
Key exclusion criteria included having known active or suspected autoimmune diseases; having received immunosuppressive agents or systemic/absorbable corticosteroid medications; having undergone any prior organ transplant; a diagnosis of other malignant tumors within 5 years, except for skin basal cell and squamous cell carcinoma; or the presence of symptomatic central nervous system metastases.
In the dose-escalation portion of the trial, a total of 12 patients received 5 mg/kg (n = 3), 10 mg/kg (n = 3), or 15 mg/kg (n = 6) of socazolimab every 2 weeks. In the dose-expansion portion of the research, an additional 91 patients were administered socazolimab at 5 mg/kg every 2 weeks.
The primary end point of the dose-escalation portion of the trial was safety and tolerability. The objectives of the dose-expansion portion of the study included ORR, PFS, DOR, OS, and safety.
At a follow-up date of March 31, 2021, a total of 104 patients were successfully enrolled to the study; these patients comprised the safety analysis set. Of the 91 patients who comprised the efficacy analysis set in the dose-expansion phase of the trial, 9 were still receiving treatment; 13 patients had completed treatment and 69 had discontinued. The most common reason for discontinuation was disease progression or deterioration (n = 34), followed by patient withdrawal (n = 13), investigator decision (n = 10), toxicity (n = 6), or another unspecified reason (n = 6).
Among all patients included in the full analysis set (n = 103), the median age was 51 years (range, 31-73). Most patients had an ECOG performance status of 1 (54.4%), a PD-L1 combined positive score (CPS) of at least 1 (58.3%), squamous cell carcinoma (93.2%), lymph node metastasis (54.4%), and received 1 prior line of treatment (52.4%). However, 29.1% of patients had received 2 prior lines of treatment and 18.4% received 3 or more prior lines.
Additional data from the dose-expansion phase of the trial showed that those with a PD-L1 combined CPS of at least 10 (n = 30) achieved an ORR of 20% (95% CI, 7.71%-38.57%) with socazolimab. In this subset, the median PFS was 7.56 months (95% CI, 2.56–not estimable [NE]), the median OS was NE (95% CI, 13.34-NE), and the 6-month and 12-month OS rates were 93.3% (95% CI, 75.9%-98.3%) and 77.0% (95% CI, 55.3%-89.1%), respectively.
In those with a CPS of at least 1 and less than 10 (n = 30), socazolimab produced an ORR of 12.5% (95% CI, 2.7%-32.4%). These patients experienced a median PFS of 3.58 months (95% CI, 2.00-7.66); the median OS was NE (95% CI, 8.54-NE). Moreover, the 6-month OS rate in these patients was 74.2% (95% CI, 51.3%-87.5%) and the 12-month OS rate was 53.0% (95% CI, 23.3%-75.8%).
In the subset of patients with a CPS of less than 1, the median PFS was 2.79 months (95% CI, 1.81-5.72), the median OS was 15.84 months (95% CI, 7.10-NE), and the 6-month and 12-month OS rates were 74.7% (95% CI, 54.1%-87.1%) and 59.3% (95% CI, 36.6%-76.3%), respectively.
The median DOR was NE across all subsets.
Among those who received the 5-mg/kg dose of socazolimab, 62.1% of patients experienced any-grade treatment-related adverse effects (TRAEs) and 8.4% experienced grade 3 or higher TRAEs. Immune-related AEs (irAEs) of any grade were reported in 35.8% of patients, and grade 3 or higher irAEs occurred in 4.8% of patients.
The most common TRAEs of any grade were hypothyroidism (16.8%), leukopenia (9.5%), elevated alanine aminotransferase (ALT; 9.5%), elevated aspartate aminotransferase (AST; 9.5%), anemia (7.4%), elevated rheumatoid factor (5.3%), nausea (5.3%), and hyperthyroidism (5.3%).
The most frequently experienced grade 3 or higher TRAEs included elevated ALT (1.1%), elevated AST (1.1%), nausea (1.1%), elevated y-glutamyltransferase (1.1%), abnormal liver function (1.1%), and vomiting (1.1%).
No dose-limiting toxicities were reported in any of the treatment groups, and the maximum tolerated dose of socazolimab was not yet reached in the highest treatment group, which was 15 mg/kg. Notably, no treatment-related deaths occurred.