GSK (LSE:GSK) has reported that its immunotherapy treatment Jemperli achieved a complete response in 76% of evaluable patients with a specific form of locally advanced rectal cancer in an exploratory analysis of the Phase II AZUR-1 clinical trial.
The study evaluated Jemperli, also known as dostarlimab, as a standalone treatment for adults with stage II or III rectal cancer characterised by mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H).
Of the 144 evaluable patients, 110 achieved a complete response, including patients whose tumours were no longer detectable through clinical assessment and those whose response was confirmed through examination of surgically removed tissue.
The findings suggest that some patients with this cancer subtype may be able to avoid chemotherapy, radiotherapy and surgery, although longer-term follow-up remains necessary.
GSK also released results from a separate Phase I study of its investigational antibody-drug conjugate mocertatug rezetecan in patients with platinum-resistant ovarian cancer.
Both datasets are scheduled for presentation at the European Society for Medical Oncology congress in Madrid.
Jemperli Achieves Complete Response in 110 of 144 Patients
The AZUR-1 study assessed Jemperli monotherapy in patients with locally advanced rectal cancer carrying the MSI-H/dMMR genetic characteristic.
This tumour subtype has deficiencies in the cellular mechanisms responsible for repairing certain forms of DNA damage.
In an exploratory analysis, 110 of 144 evaluable patients achieved a complete response, equivalent to approximately 76%.
The results included patients who experienced a complete clinical response without undergoing surgery, as well as patients whose complete response was established through pathological examination following surgery.
Investigators reported that 68% of evaluable patients achieved a complete clinical response that lasted at least 12 months without surgical intervention.
A further 12 patients had a complete pathological response confirmed following surgery, with no cancer detected in the tissue examined.
GSK said no cancer recurrences had been reported among patients who achieved a response after a median follow-up period exceeding two years.
The company noted that the findings were based on an exploratory analysis and that follow-up data continued to mature.
AZUR-1 Meets Primary Clinical Response Endpoint
The Phase II AZUR-1 trial met its primary objective of demonstrating a clinically meaningful proportion of patients achieving a complete response lasting at least 12 months.
According to an independent central review, 47% of evaluable patients had achieved this endpoint at the time of the analysis.
An additional 38 patients had experienced a complete response but had not yet reached the 12-month duration required for inclusion in the primary endpoint assessment.
The difference between the exploratory complete response rate of 76% and the independently assessed 12-month response figure reflects differences in assessment criteria and the duration of available follow-up.
GSK said the data remain immature for some patients, meaning additional responses may become eligible for the 12-month assessment as follow-up continues.
The trial evaluated Jemperli as a standalone treatment rather than in combination with conventional chemotherapy or radiotherapy.
The findings provide additional clinical evidence supporting the use of immunotherapy in patients with MSI-H/dMMR locally advanced rectal cancer.
Jemperli Safety Results Show 20% Serious Adverse Reaction Rate
GSK also reported safety findings from the AZUR-1 study.
Serious adverse reactions occurred in 20% of patients receiving Jemperli.
Approximately 3% of patients discontinued treatment because of adverse effects.
The company did not provide a detailed breakdown of individual serious adverse reactions in the reported results.
Hesham Abdullah, GSK’s Global Head of Oncology Research and Development, said the findings indicated that some patients could potentially avoid chemotherapy, radiotherapy and surgery.
The company said the results support the recent US regulatory approval of Jemperli for this treatment setting.
Continued monitoring will be required to assess the durability of responses and longer-term safety outcomes.
GSK Reports 62% Response Rate for Experimental Ovarian Cancer Treatment
Separately, GSK announced results from the Phase I BEHOLD-1 clinical trial evaluating mocertatug rezetecan, also known as Mo-Rez, in patients with platinum-resistant ovarian cancer.
Mo-Rez is an investigational antibody-drug conjugate designed to deliver a cancer treatment directly to targeted cells.
At the dose selected for Phase III development, the treatment achieved a confirmed objective response rate of 62%.
The median duration of response was 12.2 months, indicating that half of the responding patients experienced a response lasting at least that long.
Median progression-free survival was 11.1 months, representing the time during which patients remained alive without their disease progressing.
The findings relate to an early-stage clinical study, and further investigation will be needed to establish the treatment’s efficacy and safety in larger patient populations.
Mo-Rez Safety Findings Include Blood-Related Adverse Events
The BEHOLD-1 trial also reported treatment-related adverse events associated with Mo-Rez.
Grade 3 or higher treatment-related adverse events occurred in 71% of patients, with most involving blood-related complications.
Approximately 2% of patients discontinued treatment because of adverse effects.
Lung inflammation was reported in 2% of patients.
The reported safety findings will form part of the ongoing evaluation of the treatment as it progresses through later-stage clinical development.
GSK has not provided a timetable for regulatory submissions based on the BEHOLD-1 findings.
Five Phase III Trials Underway for Mo-Rez
GSK acquired rights to mocertatug rezetecan from Hansoh Pharma as part of its oncology development activities.
The company currently has five pivotal Phase III clinical trials underway involving the investigational treatment.
These studies are intended to provide additional evidence on efficacy and safety in larger patient populations.
The BEHOLD-1 findings provide early clinical data at the dose selected for further development, but the treatment remains investigational.
GSK intends to present the latest Mo-Rez results alongside the AZUR-1 Jemperli findings at the European Society for Medical Oncology congress in Madrid.
The two clinical programmes represent different stages of development within GSK’s oncology portfolio, with Jemperli already approved in the United States for the specified rectal cancer setting and Mo-Rez undergoing further clinical evaluation.
Leave a Reply