Dostarlimab for Colon Cancer

(AZUR-2 Trial)

Recruiting at 275 trial locations

Overseen By US GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: GlaxoSmithKline

Must not be taking: Anticancer, Experimental therapies

Disqualifiers: Metastatic disease, Lung disease, Cirrhosis, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: Pre and post surgery

811 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of the experimental drug dostarlimab compared to standard treatments for a specific type of colon cancer. The focus is on untreated colon cancer that can be surgically removed. Participants will receive either dostarlimab or standard treatments such as FOLFOX (a chemotherapy regimen) or CAPEOX (a combination of capecitabine and oxaliplatin, both chemotherapy drugs). This trial suits those with newly diagnosed colon cancer that meets specific criteria, such as having a tumor with particular genetic markers (dMMR/MSI-H). As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on any other anticancer or experimental therapy while participating.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that dostarlimab is safe in studies involving various cancer types. This treatment effectively fights cancer cells. While dostarlimab aids the immune system in attacking cancer, it may cause side effects such as tiredness, nausea, or changes in liver function. These side effects are usually manageable.

The standard treatments, CAPEOX and FOLFOX, are well-known chemotherapy regimens. They have been widely used and are generally well-tolerated, though they can cause side effects like hair loss, nausea, and tiredness.

Overall, both dostarlimab and the standard treatments have been studied for safety, with dostarlimab showing promising results in earlier trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Dostarlimab for colon cancer because it works differently than the standard chemotherapy treatments like FOLFOX and CAPEOX. Dostarlimab is a type of immunotherapy that targets and blocks the PD-1 protein, which cancer cells use to hide from the immune system. This approach can potentially help the immune system recognize and attack cancer cells more effectively. Unlike traditional chemotherapy, which directly kills rapidly dividing cells, Dostarlimab engages the body's own defenses to fight the cancer, offering a potentially more targeted and less toxic treatment option.

What evidence suggests that this trial's treatments could be effective for colon cancer?

Research has shown that dostarlimab, which participants in this trial may receive, effectively treats certain types of cancer. In one study, it completely eliminated cancer in all patients with mismatch repair-deficient (dMMR) cancers. Another study found that 82% of patients showed no signs of cancer after treatment, and 92% remained cancer-free for two years when treated early. These findings suggest that dostarlimab could effectively treat colon cancer with similar genetic traits, offering hope for patients with dMMR/MSI-H colon cancer. Meanwhile, participants in the standard of care arm will receive FOLFOX or CAPEOX, or undergo expectant observation post-surgery. ^{6 7 8 9 10}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Are You a Good Fit for This Trial?

This trial is for individuals with untreated T4N0 or Stage III colon cancer that can be surgically removed and shows either dMMR status or MSI-H. Participants should not have had any prior treatments for colon cancer, no distant metastatic disease, and must not require urgent surgery due to bowel obstruction.

Inclusion Criteria

Has radiologically evaluable disease

I have an untreated colon cancer diagnosis.

My tumor is identified as dMMR or MSI-H.

Exclusion Criteria

I have not had major surgery or serious injuries in the last 28 days.

Is pregnant, breastfeeding, or expecting to conceive children within the projected duration of the study

My cancer has spread to distant parts of my body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Dostarlimab pre and post surgery or Standard of Care (FOLFOX/CAPEOX) or undergo expectant observation post surgery

Pre and post surgery

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 5 years

What Are the Treatments Tested in This Trial?

Interventions

• CAPEOX
• Dostarlimab
• FOLFOX

Trial Overview The study tests the effectiveness of dostarlimab given around the time of surgery compared to standard chemotherapy regimens (CAPEOX or FOLFOX) in patients with specific types of resectable colon cancer. The goal is to see if dostarlimab improves outcomes.

How Is the Trial Designed?

Group I: Dostarlimab Experimental Treatment 1 Intervention

Participants will receive Dostarlimab pre and post surgery

Group II: Standard of Care (SOC) Active Control 2 Interventions

Participants will receive SOC (FOLFOX/CAPEOX) or undergo expectant observation post surgery.

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

Approved in United States as CAPOX/XELOX for:

• Advanced colorectal cancer

Approved in European Union as CAPOX/XELOX for:

• Colorectal cancer
• Stomach cancer
• Cancer of the food pipe (oesophagus)

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

In a study of 394 patients with stage III colon cancer, CAPOX was found to improve disease-free survival compared to FOLFOX, with a 3-year disease-free survival rate of 83.8% versus 73.4%.

FOLFOX was associated with higher rates of mucositis and neutropenia, while CAPOX led to more dose-limiting toxicities and diarrhea, indicating that while CAPOX may offer better long-term outcomes, it also comes with increased side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival Impact of CAPOX Versus FOLFOX in the Adjuvant Treatment of Stage III Colon Cancer. Loree, JM., Sha, A., Soleimani, M., et al.[2019]

The XELOXGEM regimen, combining capecitabine, oxaliplatin, and gemcitabine, was found to be an effective second-line treatment for advanced colorectal carcinoma (CRC) patients who had previously been treated with irinotecan, showing a median overall survival of 17.7 months.

The recommended dose for gemcitabine was established at 600 mg/m² due to dose-limiting toxicities observed at higher doses, with common side effects including neutropenia and thrombocytopenia, indicating that while the treatment is active, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining capecitabine, oxaliplatin, and gemcitabine (XELOXGEM) for colorectal carcinoma patients pretreated with irinotecan: a multicenter phase I/II trial. Kim, SH., Shin, SJ., Kim, SY., et al.[2022]

The modified CAPOX regimen, which combines capecitabine and oxaliplatin, was found to be a safe and effective salvage treatment for advanced colorectal cancer, with an overall response rate of 24% among 67 patients studied.

Patients experienced manageable side effects, with only 6% experiencing severe neutropenia and 3% severe thrombocytopenia, while the median overall survival was 11.3 months, indicating a beneficial outcome after prior irinotecan treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified CAPOX (capecitabine plus oxaliplatin) regimen every two weeks as second-line treatment in patients with advanced colorectal cancer previously treated with irinotecan-based frontline therapy: a multicenter phase II study. Kakolyris, S., Souglakos, J., Polyzos, A., et al.[2018]

A meta-analysis of 10 randomized controlled trials involving 3208 patients found that capecitabine plus oxaliplatin (CAPOX) is as effective as fluorouracil plus oxaliplatin (FUOX) in treating metastatic colorectal cancer, showing no significant differences in tumor response rate, progression-free survival, or overall survival.

However, the CAPOX regimen was associated with a higher incidence of side effects such as thrombocytopenia and hand-foot syndrome, while FUOX led to more cases of neutropenia and leucopenia, indicating that while both treatments are effective, their safety profiles differ.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine/oxaliplatin as first-line treatment for metastatic colorectal cancer: a meta-analysis. Zhao, G., Gao, P., Yang, KH., et al.[2018]

In a clinical trial involving 40 patients with KRAS wild type metastatic colorectal cancer, the combination of cetuximab and XELOX achieved a confirmed overall response rate of 50%, indicating significant efficacy in treating this condition.

The safety profile of the treatment was acceptable, with common Grade 3/4 adverse events including acneiform eruption (12.5%) and peripheral neuropathy (7.5%), but no deaths were reported within 30 days of treatment, suggesting a manageable safety risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Study of XELOX and Cetuximab as First-Line Therapy in Patients With KRAS Wild Type Metastatic Colorectal Cancer (FLEET2 Study). Hazama, S., Maeda, H., Iwamoto, S., et al.[2022]

In a study of 94 patients aged 70 and older with advanced colorectal cancer, both CAPOX and CAPIRI treatments showed similar overall response rates (38% for CAPOX and 36% for CAPIRI), indicating comparable efficacy as first-line treatments.

CAPOX was better tolerated than CAPIRI, with fewer severe side effects such as diarrhea and neutropenia, suggesting it may be a safer option for elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine in combination with oxaliplatin or irinotecan in elderly patients with advanced colorectal cancer: results of a randomized phase II study. Rosati, G., Cordio, S., Bordonaro, R., et al.[2020]

In a phase III trial involving 1,886 patients with stage III colon cancer, the combination of capecitabine and oxaliplatin (XELOX) demonstrated a manageable safety profile, with treatment-related adverse events occurring at similar rates to the standard treatment of fluorouracil/leucovorin (FU/LV).

Patients receiving XELOX experienced less diarrhea and alopecia but had higher rates of neurosensory toxicity and hand-foot syndrome compared to those on FU/LV, indicating that while XELOX is generally well-tolerated, it may have specific side effects that need monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III trial of capecitabine plus oxaliplatin as adjuvant therapy for stage III colon cancer: a planned safety analysis in 1,864 patients. Schmoll, HJ., Cartwright, T., Tabernero, J., et al.[2022]

Adjuvant XELOX treatment (oxaliplatin plus capecitabine) is tolerable for Japanese patients with curatively resected stage III colon cancer, with a treatment completion rate of 73.7% based on a study involving 196 patients over 34 months.

The most common side effect was peripheral sensory neuropathy (PSN) occurring in 88.4% of patients, but there were no treatment-related deaths, indicating a manageable safety profile for this chemotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interim analysis of a phase II trial evaluating the safety and efficacy of capecitabine plus oxaliplatin (XELOX) as adjuvant therapy in Japanese patients with operated stage III colon cancer. Danno, K., Hata, T., Tamai, K., et al.[2022]

In a study involving 2,034 patients, capecitabine plus oxaliplatin (XELOX) was found to be noninferior to fluorouracil, folinic acid, and oxaliplatin (FOLFOX-4) in terms of progression-free survival, with median times of 8.0 months for XELOX and 8.5 months for FOLFOX-4.

XELOX demonstrated a similar overall survival rate (19.8 months) compared to FOLFOX-4 (19.6 months) but had a more favorable safety profile, causing fewer instances of severe neutropenia while leading to more cases of diarrhea and hand-foot syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. Cassidy, J., Clarke, S., Díaz-Rubio, E., et al.[2022]

In a phase II trial involving 46 patients with metastatic colorectal cancer, two different dosing regimens of capecitabine and oxaliplatin showed no significant differences in treatment efficacy, with a median time-to-treatment failure of 3.4 months for both regimens.

Safety profiles were similar, with common severe side effects including fatigue and neuropathy, but no significant differences in adverse events between the two treatment groups, indicating that neither regimen was more effective or safer than the other.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter randomized phase II clinical trial of oxaliplatin reintroduction as a third- or later-line therapy for metastatic colorectal cancer-biweekly versus standard triweekly XELOX (The ORION Study). Matsuda, C., Honda, M., Tanaka, C., et al.[2020]

In a study of 50 patients with nonmetastatic colorectal cancer, adverse reactions were more frequent with the XELOX regimen (capecitabine combined with oxaliplatin), particularly neurotoxicity, thrombocytopenia, and neutropenia, compared to capecitabine monotherapy.

The type of capecitabine formulation (innovative vs. generic) did not significantly affect the safety profile; instead, the chemotherapy scheme used was the main factor influencing the occurrence of adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine safety profile, innovative and generic adjuvant formulation of nonmetastatic colorectal cancer. Sánchez-Gundín, J., Torres-Suárez, AI., Fernández-Carballido, AM., et al.[2020]

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 ... The trial showed an unprecedented 100% clinical complete response rate (cCR) in 42 patients who completed treatment with dostarlimab.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9433597/

Dostarlimab: The miracle drug for the treatment of ... These groundbreaking results are unforeseen in cancer research according to some experts [8]. These patients went through treatments like chemotherapy, ...

3. 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 ...

4. 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.

5. 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 ...

6. gsk.com gsk.com/media/tbpjzzcy/jemperli-fda-btd-press-release-161224.pdf

jemperli-fda-btd-press-release-161224.pdf Jemperli (dostarlimab) receives US FDA Breakthrough. Therapy Designation for locally advanced dMMR/MSI-H rectal cancer.

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

Jemperli (Dostarlimab-gxly): An unprecedented cancer trial This drug has been used for multiple cancers and has been considered safe with substantial survival rates of patients. Significant clinical activity has been ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02715284

NCT02715284 | Study of TSR-042, an Anti-programmed ... Part 2B of the study will examine the safety and clinical activity of dostarlimab in cohorts of participants with specific types of advanced solid tumors.

9. mayoclinic.org mayoclinic.org/drugs-supplements/dostarlimab-gxly-intravenous-route/description/drg-20514856

Dostarlimab-gxly (intravenous route) - Side effects & uses Dostarlimab-gxly is a monoclonal antibody that changes the immune system to help control the growth of cancer cells.

10. aetna.com aetna.com/cpb/medical/data/900_999/0993.html

Dostarlimab-gxly (Jemperli) - Medical Clinical Policy Bulletins Aetna considers dostarlimab-gxly (Jemperli) medically necessary as a single agent for treatment of colorectal cancer, including appendiceal adenocarcinoma and ...