Dostarlimab for Rectal Cancer

(AZUR-1 Trial)

Recruiting at 62 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

154 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a drug called dostarlimab on patients with a specific type of rectal cancer who haven't been treated before. The goal is to see if this drug alone can treat the cancer effectively, so patients might avoid more aggressive treatments like chemotherapy, radiation, and surgery. Dostarlimab (Jemperli™) has been approved in the EU and USA for treating certain types of cancer.

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.

What data supports the effectiveness of the drug dostarlimab for rectal cancer?

In a clinical trial, dostarlimab showed a 100% remission rate in patients with mismatch repair-deficient rectal cancer, meaning all patients experienced a complete response without needing surgery, chemotherapy, or radiotherapy. ^{1 2 3 4 5}

Is dostarlimab safe for humans?

Dostarlimab has been approved by the FDA for certain types of cancer, and in a trial for rectal cancer, it showed promising results with no patients experiencing cancer progression or recurrence. However, as with any medication, there may be side effects, and its safety continues to be evaluated in ongoing trials. ^{1 2 3 5 6}

What makes the drug dostarlimab unique for treating rectal cancer?

Dostarlimab is unique because it is an immunotherapy drug that targets the PD-1 receptor, and in a clinical trial, it achieved a 100% remission rate in patients with mismatch repair-deficient rectal cancer, allowing them to avoid traditional treatments like chemotherapy, radiotherapy, or surgery. ^{1 2 3 4 5}

Research Team

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Eligibility Criteria

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).

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

Participant has radiologically and endoscopically evaluable disease

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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-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]

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]

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, 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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Dostarlimab: A Review. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Dostarlimab: First Approval. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

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

4. United States pubmed.ncbi.nlm.nih.gov

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

5. England 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. [2022]

6. United States 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. [2023]