Dostarlimab for Rectal Cancer

(AZUR-1 Trial)

Not currently recruiting at 68 trial locations

Overseen By EU GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: GlaxoSmithKline

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Metastatic disease, Autoimmune, Allergies, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 33 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests an experimental drug called dostarlimab (also known as Jemperli) to determine its effectiveness in treating rectal cancer without chemotherapy, radiation, or surgery. The focus is on individuals with a specific type of rectal cancer known as dMMR or MSI-H, where cancer cells struggle to repair DNA. Those diagnosed with locally advanced rectal cancer, who have not received previous treatments, and whose cancer is visible on scans might be suitable candidates. The goal is to see if dostarlimab alone can help patients avoid more aggressive treatments while monitoring for any recurrence of the disease. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have an active autoimmune disease that required treatment in the past 2 years, you may not be eligible to participate.

Is there any evidence suggesting that dostarlimab is likely to be safe for humans?

Research shows that dostarlimab is generally safe for treating certain cancers. In earlier studies, patients with advanced rectal cancer who took dostarlimab showed no signs of the disease, indicating the drug's effectiveness without causing serious harm. Another study found that dostarlimab was well-tolerated and helped improve survival rates for cancer patients.

Although this study focuses on rectal cancer, dostarlimab has been safely used for other cancers as well. Results suggest it is a promising option, with patients responding well and experiencing manageable side effects. However, individual reactions can differ. It is important to discuss potential risks and benefits with a healthcare provider before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Dostarlimab is unique because it is a type of immunotherapy known as a PD-1 inhibitor, which works by unleashing the body's immune system to attack cancer cells. This mechanism is different from traditional chemotherapy and radiation treatments for rectal cancer, which directly target and kill cancer cells but can also harm healthy cells. Researchers are excited about dostarlimab because it has the potential to offer a more targeted approach with fewer side effects, as it aims to harness the body's natural defenses. Additionally, early results have shown promising effectiveness, making it a potential game-changer in rectal cancer treatment.

What evidence suggests that dostarlimab might be an effective treatment for rectal cancer?

Research has shown that dostarlimab holds promise for treating mismatch repair deficient (dMMR) rectal cancer. In one study, 82% of patients experienced a complete response, with their cancer no longer detectable after treatment. Furthermore, 92% of patients remained cancer-free for at least two years. In this trial, participants will receive dostarlimab monotherapy. These findings suggest that dostarlimab could serve as an effective treatment option, potentially allowing patients to avoid traditional treatments like chemotherapy and surgery. ^{1 2 4 6 7}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Are You a Good Fit for This Trial?

This trial is for adults with Stage II to III locally advanced rectal cancer that hasn't spread and hasn't been treated yet. Their tumors must be dMMR or MSI-H. People can't join if they've had prior treatments for their cancer, certain severe reactions to immunotherapy, other recent cancers (except some skin/bladder/in situ cancers), known allergies to dostarlimab or its parts, recent organ transplants, distant metastases, active autoimmune diseases needing treatment in the last 2 years, or lung disease/pneumonitis.

Inclusion Criteria

My rectal cancer is advanced but hasn't spread far (Stage II to III).

Participant has radiologically and endoscopically evaluable disease

My tumor is identified as mismatch repair deficient or has high microsatellite instability.

Exclusion Criteria

I have another cancer besides the one being studied, but it hasn't needed treatment in the last 2 years, except for certain skin, bladder cancers, or cancers that haven't spread.

I have an autoimmune disease treated with medication in the last 2 years.

I have had or plan to have a transplant with donor stem cells.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dostarlimab monotherapy to achieve complete clinical response

Up to 33 weeks

Non-operative Management (NOM)

Participants undergo close surveillance for recurrent disease after achieving complete clinical response

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 74 months

What Are the Treatments Tested in This Trial?

Interventions

• Dostarlimab

Trial Overview The study tests Dostarlimab as a solo therapy on patients with specific types of advanced rectal cancer. The aim is to see if this drug alone can effectively treat the cancer without needing chemotherapy, radiation, or surgery. Patients who respond completely will be monitored closely instead of undergoing traditional treatments.

How Is the Trial Designed?

Group I: Dostarlimab monotherapy Experimental Treatment 1 Intervention

Dostarlimab is already approved in European Union, United States for the following indications:

Approved in European Union as Jemperli for:

• Mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer
• dMMR/MSI-H recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum-containing regimen

Approved in United States as Jemperli for:

• Adults with dMMR recurrent or advanced solid tumors who have progressed on or following prior treatment and lack satisfactory alternative treatment options
• Primary advanced or recurrent dMMR endometrial cancer in combination with carboplatin and paclitaxel

Who Is Running the Clinical Trial?

GlaxoSmithKline

Lead Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Published Research Related to This Trial

Dostarlimab (JEMPERLI) is a PD-1 monoclonal antibody that has received rapid FDA approval for treating adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer, showing promising tumor response rates.

A clinical trial (NCT04165772) reported a remarkable 100% remission rate for rectal cancer patients treated with Dostarlimab, highlighting the potential of matching tumor genetics with targeted therapies, and the trial is ongoing for other cancer types like gastric, prostate, and pancreatic cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab: A Review. Costa, B., Vale, N.[2022]

In a phase II trial involving 12 patients with mismatch repair-deficient, locally advanced rectal cancer, dostarlimab resulted in a remarkable 100% clinical complete response, with no disease progression or recurrence observed so far.

All patients treated with dostarlimab did not require traditional treatments like chemotherapy, radiotherapy, or surgery, suggesting a potentially groundbreaking approach to cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel trial methodology to test interventions with very large effect sizes: the case of dostarlimab in mismatch repair-deficient, locally advanced rectal cancer. Powell, K., Olivier, T., Prasad, V.[2022]

Dostarlimab-gxly (Jemperli) has received accelerated approval from the FDA for treating adults with mismatch repair deficient recurrent or advanced endometrial cancer and solid tumors, indicating its potential effectiveness in these specific cancer types.

This approval highlights the importance of targeted therapies in oncology, particularly for patients with specific genetic markers that may influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Drug for Mismatch Repair Deficient Endometrial Cancer and Solid Tumors. Aschenbrenner, DS.[2023]

Dostarlimab is a monoclonal antibody that targets the PD-1 receptor and has been approved for treating adult patients with mismatch repair deficient recurrent or advanced endometrial cancer based on promising results from the GARNET trial.

The approval of dostarlimab in the EU and USA marks a significant milestone in cancer treatment, highlighting its potential efficacy in targeting specific cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab: First Approval. Markham, A.[2021]

Dostarlimab, an anti-PD-1 monoclonal antibody, has been shown to be equipotent to pembrolizumab in suppressing PD-1 activity, with an estimated effective concentration of 1.95 μg/ml based on data from the GARNET trial.

The recommended dosing regimen for dostarlimab is 500 mg every 3 weeks for 4 cycles, followed by 1000 mg every 6 weeks, which supports its use as a potent treatment option for patients with recurrent or advanced mismatch repair-deficient solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative analysis of PD-1 target engagement of dostarlimab and pembrolizumab in advanced solid tumors using ex vivo IL-2 stimulation data. Austin, D., Melhem, M., Gandhi, Y., et al.[2023]

Neoadjuvant treatment with the immunotherapy dostarlimab has shown remarkable clinical responses in patients with mismatch repair (MMR)-deficient rectal cancers, potentially allowing some patients to avoid surgery altogether.

This study highlights the efficacy of dostarlimab as a promising treatment option for this specific type of rectal cancer, suggesting a significant advancement in cancer care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Defying all odds in MMR-deficient rectal cancers. Chalabi, M.[2022]

Citations

1. gsk.com gsk.com/en-gb/media/press-releases/jemperli-dostarlimab-trial-continues-to-show-unprecedented-results/

Jemperli (dostarlimab) trial continues to show ... GSK is advancing studies evaluating dostarlimab in patients with advanced/metastatic stages of dMMR/MSI-H colorectal cancer through its AZUR ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9289402/

Jemperli (Dostarlimab-gxly): An unprecedented cancer trial Recently, it was known to have had a positive effect on treatment of colorectal cancer according to data from a phase 2 clinical trial; 12 patients with stage ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1533002825000246

Clinical Colorectal Cancer A recent study demonstrated that dostarlimab, an immune-checkpoint inhibitor, was highly effective in treating mismatch repair deficient (dMMR) locally advanced ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2201445

PD-1 Blockade in Mismatch Repair–Deficient, Locally ... In our study, single-agent dostarlimab was remarkably effective in mismatch repair–deficient, locally advanced rectal cancer, providing a ...

5. onclive.com onclive.com/view/dostarlimab-yields-high-ccr-rates-and-organ-preservation-in-early-stage-dmmr-tumors

Dostarlimab Yields High cCR Rates and Organ ... Neoadjuvant dostarlimab led to an 82% clinical complete response and a 92% 2-year RFS rate, supporting nonoperative management in early-stage dMMR tumors.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05723562

NCT05723562 | A Study of Dostarlimab in Untreated ... The purpose of this study is to investigate dostarlimab monotherapy in participants with locally advanced Mismatch-repair deficient (dMMR)/Microsatellite ...

7. cancernetwork.com cancernetwork.com/view/dostarlimab-gxly-granted-breakthrough-therapy-designation-for-rectal-cancer

Dostarlimab-gxly Granted Breakthrough Therapy ... Dostarlimab achieved a 100% clinical complete response rate in patients with dMMR/MSI-H advanced rectal cancer, a phase 2 study found.