GSK Reports 100% Complete Response with PD-1 Inhibitor Jemperli in dMMR Rectal Cancer and Plans FDA Resubmission for BCMA ADC Blenrep
GSK
Pharmaceutical R&D Manufacturer
On June 3, GSK announced its PD-1 inhibitor Jemperli（dostarlimab）Alternative Surgery for Mismatch Repair Deficiency（dMMR）Latest Long-term Data from Phase II Clinical Trial of First-line Therapy for Locally Advanced Rectal Cancer.
Data shows,42 Patients Completing Jemperli Treatment Achieved an Unprecedented 100% Clinical Complete Response Rate (cCR)In the initial assessment of 24 patients, sustained clinical complete remission was observed, with a median follow-up of 26.3 months. The safety and tolerability profile of Jemperli was generally consistent with the known safety profile of the drug, and no grade 3 or higher adverse events were reported in this trial. Detailed data will be presented at ASCO.
For dMMR/High Microsatellite Instability（MSI-H）Current Standard Treatment for Locally Advanced Rectal Cancer（SoC）The initial treatment is chemotherapy + radiotherapy, followed by surgical removal of the tumor along with part of the intestine and/or surrounding tissues. Although patients may initially achieve positive outcomes, nearly one-third will eventually die from distant cancer metastases. Additionally, surgeries and chemoradiotherapy associated with the standard of care (SoC) can have significant negative impacts, including intestinal, urinary, and sexual dysfunction, secondary cancers, infertility, and more.
GSK is advancing the application of Jemperli in patients with advanced/metastatic dMMR/MSI-H colorectal cancer through the AZUR series of clinical trials.
The followingAZUR-1 TrialIt is a global, multicenter, open-label Phase II registrational clinical trial aimed at investigating the efficacy and safety of Jemperli monotherapy as an alternative to chemotherapy, radiotherapy, and/or surgery for the treatment of previously untreated dMMR/MSI-H locally advanced rectal cancer patients.AZUR-2A Phase III, Open-label, Randomized Study of Perioperative Dostarlimab Monotherapy Versus Standard of Care in Previously Untreated Patients with T4N0 or Stage III dMMR/MSI-H Resectable Colon Cancer.
In addition to this surprising data, GSK also announced at the ASCO conference on Saturday thatADC Drug BlenrepPositive results demonstrated in multiple myeloma.
In the second Phase III trial, DREAMM-8, Blenrep was compared to the standard of care for second-line treatment of multiple myeloma. The results showed that, compared with Takeda's Velcade（V）BMS's Pomalyst（P）And Dexamethasone（d）Compared to the combination, Blenrep reduced the risk of cancer progression or death by 48%.
After a median follow-up of 21.8 months, the PFS in the Blenrep group has not been reached, while the PFS in the control group was 12.7 months.
Previously, data from the DREAMM-7 trial showed that, in their respective pairings with Vd, Blenrep's PFS outperformed Johnson & Johnson's Darzalex.（D）59% higher. The study also tested second-line or later treatment regimens.
GSK's R&D head Hesham Abdullah said that with the success of the two trials,GSK Plans to Submit Blenrep Application to FDA in Second Half of This Year, Hoping to Relaunch the ADC Product in the U.S.
In November 2022, the confirmatory Phase III trial DREAMM-3 for Blenrep failed, and GSK withdrew Blenrep from the U.S. market at the request of the FDA. The drug's market expansion in EU countries also faced challenges after the EMA refused to grant full approval in September 2023.
After the data from DREAMM-8 was released, Oreofe Odejide from the Dana-Farber Cancer Institute, as an expert invited by ASCO, stated that the data supports the return of Blenrep as a treatment option for relapsed myeloma.
If approved, Blenrep will compete with Johnson & Johnson and Legend Biotech's BCMA CAR-T therapy Carvykti in second-line treatment and contend with BMS's Abecma for subsequent treatments.
Through a comparative cross-trial analysis, the 48% PFS benefit observed with Blenrep in the latest DREAMM-8 trial appears smaller than the 59% result achieved by Carvykti in the CARTITUDE-4 trial, which used PVd or DPd as the control group.
In this regard, Abdullah is optimistic and stated that the early DREAMM-7 study could achieve statistical significance in overall survival. In the previous interim analysis, compared with PVd, Blenrep-Vd initially reduced the risk of death by 43%. At that time, the data was very close to reaching statistical significance.
In the ongoing DREAMM-8 trial, Blenrep showed a favorable trend of reducing the risk of death by 23% at the interim analysis. Abdullah said that GSK expects the scale of benefit to expand over time but did not express the same level of confidence regarding achieving statistical significance.
Abdullah also pointed out some important differences between the two trials. In DREAMM-7, about half of the trial participants had previously tried BMS's Revlimid, including 30% who were refractory to immunomodulatory agents. In the DREAMM-8 trial, all patients had previously tried Revlimid, including 80% who were refractory.
GSK executive said, "Acquisition, consistency of efficacy, efficacy across multiple patient subgroups, and overall survival" will be the key features of Blenrep.
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