A cancer drug trial with 100% success rate: What we know about dostarlimab

It is reported as one of the most surprising developments in cancer treatment and research. All the 12 rectal cancer patients who took part in a clinical trial were found completely cured of the disease after they took the drug dostarlimab for six months. They were fighting locally advanced form of rectal cancer at the Memorial Sloan Kettering Cancer Center in Manhattan, US. The drug, costing about $11,000 per dose, was given every three weeks for six months, according to a medical journal. At the end of the trial, they were all found cancer-free when screened through endoscopy, PET scans (positron emission tomography) and MRI scans.

"Astonishing." "Unexpected." "A miracle." 

These are some of the superlatives used to describe an exciting new drug — known as dostarlimab — used in a cancer study. Yes, it’s too early to call it a “cure”, and a further, bigger study is certainly needed.

Yet the results stumped even the researchers: a 100% remission in every one of the 12 rectal cancer patients who signed up for the clinical trial, a new study shows.

The experimental drug, a monoclonal antibody therapy, recruits the patient’s own immune cells to start fighting cancerous cells.

Dostarlimab is known by the medical research community as a “PD-1 blockade” drug and “checkpoint inhibitor”.

There were 12 patients in the trial with lab-confirmed subset of cancer known as "mismatch repair–deficient (dMMR)” locally advanced colorectal cancer.

Researchers in New York’s Memorial Sloan Kettering Cancer Centre in Manhattan have found that the drug works against dMMR colorectal cancer — in what amounts to a “programmed death” for the cancer cells.

The 100% success rate, however, was found in a small number of trial

participants — a total of 12 patients with lab-confirmed, locally-advanced solid tumour Stage II and III rectal cancer.

Cancer specialists who are not part of the research team hailed the initial findings as a potential “game-changer”.

Following are the key things to know:

It’s the first time a single-agent drug was found to work against a specific type of cancer in a clinical trial involving humans.

This is also the first time that this treatment was used for mismatch repair–deficient (dMMR) colorectal cancer, which resulted in 100% remission in every single patient.

The drug is called dostarlimab. It belongs to a class of drugs known as “immune checkpoint inhibitor”.

Essentially, it takes the breaks off of the person’s natural immune system. Dostarlimab is an anti–PD-1 monoclonal antibody (“PD” stands for “programmed death”).

It was a small clinical trial — 12 patients signed up. All were diagnosed with early-stage colorectal tumours — from Stages 1 to 3.

Here’s the reaction from some of the patients who participated in the trial.

Single-agent dostarlimab was administered every 3 weeks for 6 months in patients with mismatch repair–deficient stage II or III rectal adenocarcinoma. The trial was known as a “prospective phase 2 study”.

GlaxoSmithKline developed dostarlimab, under the brand name Jemperli.

Jemperli is the brand name of dostarlimab-gxly, which is used for the treatment of advanced solid tumours. Jemperli received approval from the US Food and Drug Administration (FDA) in 2021 for mismatch repair-deficient (dMMR) solid tumours after having been approved for the dMMR endometrial cancer indication.

Results of the study — titled “PD-1 Blockade in Mismatch Repair–Deficient, Locally Advanced Rectal Cancer” — were published June 5, 2022 in the New England Journal of Medicine.

Researchers built on previous work which found that dMMR is responsive to programmed death 1 (PD-1) blockade in the context of metastatic disease.

It was hypothesised that checkpoint blockade could be effective in patients with mismatch repair–deficient (dMMR) rectal cancer.

“This type of cancer that we treated is a subset called ‘mismatch repair-deficient’,” lead researcher Dr. Andrea Cercek, Medical Oncologist, Memorial Sloan Kettering Cancer Centre, New York, explained to CNN.

“Basically, they lack a gene that repairs DNA. So the tumours look very, very unusual. They have a lot of mutations, which effectively kind of act like flags for the immune system to recognise the cancer. So the patient’s immune system is already interested in fighting the cancer.

“When we give a checkpoint inhibitor such as dostarlimab, which is the drug that we used, it takes the breaks off of the immune system,” she added.

“It recruits a lot of immune cells and they start fighting the cancer. And in this case, they fought it so well that, in every single patient, the cancer is completely gone, just with the checkpoint inhibitor alone.”

This gene is present in 3% to 4% of other tumours that are in early stages, according to her.

Typically for rectal cancer treatment, doctors do chemotherapy, radiation and surgery. Both radiation and surgery can be debilitating: they change bowel habits, and affect sexual function, and fertility. And then in about 30% of the patients, because of the location of the tumour, when they have surgery, need a permanent colostomy. So that’s very disfiguring and really changes the patient’s life and survivorship.

The trial results are a “game-changer,” according to Alan Burguete-Torres, Gastrointestinal Medical Oncologist. Professor of Medicine and Attending Physician at University of Nuevo Leon Cancer Center, Mexico, who was not part of the study.

One report states the medication costs about $11,000 (about Dh40,700) per 500mg dose in the US.

In the UK, it is sold for £5,887.33 per 500mg vial. The UK’s National Health Service has a discounted price from manufacturer GSK as dostarlimab is already used in the treatment of advanced endometrial cancer.

While the results are promising, other experts say it’s too early to call it a “cure”.

Results will need to be repeated on a much bigger scale.

The study, however, has raised hopes the world may have found a tool against a subset of cancer.

Dr Cercek said: “What we hope to do is to be able to replicate these findings in other tumours that are mismatch repair–deficient — such as stomach cancer, pancreas cancer, bladder cancer.

“And if it works, then we could potentially spare patients surgery and radiation in those tumours as well.”