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Cancer immunotherapy basket trial leads to NICE recommendation for MSD’s KEYTRUDA (pembrolizumab) as a treatment option for adults with previously treated endometrial, biliary, colorectal, gastric and small intestine cancer with microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR)

August 22, 2023 – Clinical Trials – Keytruda, MSD, basket trial

The results from the basket trial show that pembrolizumab monotherapy demonstrates clinically meaningful data to patients with MSI-H or dMMR solid metastatic tumours, across the five tumour sites evaluated, with respect to objective response rate (ORR).
Compared to a traditional trial, a basket trial tests a drug on multiple types of cancer with the same specific molecular alteration. This can reduce the number of trials needed to help bring treatments to patients.

17 August 2023 — London, UK — MSD announced today that the National Institute for Health and Care Excellence (NICE) has recommended the use of KEYTRUDA (pembrolizumab) as an option for treating tumours with microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR) in adults with: advanced or recurrent endometrial cancer that has progressed during or after platinum-based therapy, who cannot have curative surgery or radiotherapy; unresectable or metastatic gastric, small intestine or biliary cancer that has progressed during or after one therapy; colorectal cancer after fluoropyrimidine combination therapy, only if they cannot have nivolumab with ipilimumab.

The positive decision from NICE is the first granted based on data from an immunotherapy basket trial. Compared to a traditional trial, a basket trial tests a drug on multiple types of cancer, with the same specific molecular alteration. This can reduce the number of trials needed to help bring treatments to patients.

In 2022, UK licence was granted for the indication of pembrolizumab in adults as a monotherapy across five MSI-H/dMMR tumour sites meeting specific requirements in the basket trial. This included its indication for the treatment of metastatic or unresectable MSI-H/dMMR colorectal cancer after previous fluoropyrimidine-based combination therapy. In advanced or recurrent MSI-H/dMMR endometrial carcinoma, it was licensed for the treatment of MSI-H/dMMR tumours when there is disease progression on or following prior treatment with a platinum-containing therapy in any setting, and patients are not candidates for curative surgery or radiation. In MSI-H/dMMR unresectable or metastatic gastric, small intestine, or biliary cancer, pembrolizumab was licensed for candidates with disease progression on or following at least one prior therapy.

MSI-H and dMMR are DNA features (known as tumour biomarkers) which may predispose people to different types of cancer. Tumours that contain these biomarkers are missing some normal DNA features or have faulty DNA repair. There is a high unmet need for treatments targeting MSI-H/dMMR tumours that increase survival rates in the metastatic setting. While the survival for patients diagnosed at Stage IV varies by tumour site, there is some evidence that MSI-H/dMMR status is associated with a poorer prognosis in advanced cancers compared with non-MSI-H/dMMR status.

Helen Morement, CEO of AMMF, said: “The decision by NICE is warmly welcomed by AMMF and the patients and clinical communities we support. More effective treatments are desperately needed to treat cholangiocarcinoma. This treatment option offers a small but important step forward in the treatment of some people with cholangiocarcinoma for whom, to this point, there has been so very little.”

Julie Harrington, CEO of Guts UK said: “We are delighted that some people with metastatic gastric, small intestine, biliary and colorectal cancer have gained access to an additional treatment option. As the first immunotherapy multi tumour basket trial recommended by NICE for people with these types of tumours, this decision will help address this unmet need. For eligible patients, this news will be warmly welcomed as it may help give them more time with their loved ones.”

David Long, head of Oncology at MSD UK, said: “We at MSD are delighted that NICE have approved the basket study for adults with previously treated MSI-H/dMMR tumours. MSI-H/dMMR tumours are associated with a poorer prognosis in advanced cancers, compared with non-MSI-H/dMMR status, which means there is a high unmet for patients with these gene features. The results of the basket trial for colorectal, endometrial, gastric, small intestine and biliary cancer will help to address a high unmet clinical need going forward.”

Clinical trial data

The recommendation was based on two phase 2, non-randomised, single-arm, multi-site, and open-label trials, KEYNOTE-164 (NCT02460198) and KEYNOTE-158 (NCT02628067), that investigated the use of pembrolizumab in adult patients with previously treated unresectable and/or metastatic MSI-H/dMMR solid tumours.

Clinical evidence was based on data from 124 participants with MSI-H/dMMR colorectal cancer, enrolled in two cohorts in KEYNOTE-164; an updated analysis from ESMO 2021 showed:

Treatment with pembrolizumab resulted in a median objective response rate (ORR) of 33% (95% CI, 21%, 46%) for cohort A and 35% (95% CI, 23%, 48%) for cohort B, with median duration of response not reached in either cohort.
Additionally, pembrolizumab showed a median progression-free survival (PFS) of 2.3 months (95% CI, 2.1, 8.1) and 4.1 months (95% CI, 2.1, 18.9), respectively, and a median overall survival (OS) of 31.4 months (95% CI, 21.4, 58) and 47 months (95% CI, 19.2, NR), respectively.
Treatment related adverse events (TRAEs) occurred in 64% of patients in cohort A and 71% in cohort B; grades 3/4 TRAEs in 16% and 13%, respectively. No grade 5 TRAEs occurred. Immune-mediated AEs and infusion reactions occurred in 21% of patients in cohort A and 38% in cohort B.

Clinical evidence was based on the KEYNOTE-158 data, which enrolled 233 patients and represented 27 tumour types including endometrial, gastric, small intestine and cholangiocarcinoma.

Treatment with pembrolizumab resulted in a median ORR of 34.3% (95% CI, 28.3%, 40.8%).
Additionally, pembrolizumab showed a median PFS of 4.1 months (95% CI: 2.4, 4.9) and a median OS of 23.5 months (95% CI: 13.5, NR).
151 patients (64.8%) of patients experienced a TRAE, of which 34 patients (14.6%) had grade 3 to 5 TRAEs, including one case of grade 5 pneumonia.
The most common TRAE of any grade were fatigue (n = 34; 14.6%), pruritus (n = 30; 12.9%), diarrhoea (n = 28; 12.0%), and asthenia (n = 25; 10.7%).

About AMMF

Founded in 2002, AMMF was the world’s first charity dedicated solely to cholangiocarcinoma (CCA, bile duct cancer). Today, AMMF remains the UK’s only CCA charity, now working nationally and across Europe, as well as actively collaborating globally. Over the past 21 years, AMMF has campaigned on behalf of cholangiocarcinoma patients and their loved ones, for more research and awareness of this neglected cancer.

About MSD

At MSD, known as Merck & Co., Inc., Rahway, NJ, USA in the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.msd-uk.com