Cobolimab + Dostarlimab for Cancer

Recruiting at 35 trial locations

Overseen By US GSK Clinical Trials Call Center

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: GlaxoSmithKline

Must not be taking: Immunosuppressants, Systemic steroids

Disqualifiers: Uncontrolled CNS involvement, Cardiovascular disease, Respiratory disease, others

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

Compensation: Varies

Number of Visits: Unknown

95 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this interventional study is to determine the strength of cobolimab and dostarlimab that is most tolerated in children and young adults who have advanced solid tumors. This study also aims: (a) to check if it is safe to use cobolimab and dostarlimab combination in children and young adults, (b) to see how to manage the side effects that may occur, and (c) the effect of this treatment in participants

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received any anti-cancer therapy within 30 days before joining, and you should not be on systemic steroid therapy within 3 days before the first dose of the study treatment.

What data supports the effectiveness of the drug combination Cobolimab and Dostarlimab for cancer?

Dostarlimab, also known as JEMPERLI, has shown effectiveness in treating certain types of endometrial cancer, as indicated by the ongoing GARNET study, which is assessing its safety and side effects. ^{1 2 3 4 5}

Is the combination of Cobolimab and Dostarlimab safe for humans?

Dostarlimab, also known as Jemperli, has been studied for safety in patients with endometrial cancer in the GARNET study, which is a phase 1 clinical trial. This study is ongoing and aims to understand the safety and side effects of dostarlimab. ^{4 6 7 8 9}

What makes the drug combination of Cobolimab and Dostarlimab unique for cancer treatment?

The combination of Cobolimab and Dostarlimab is unique because Dostarlimab is a PD-1 monoclonal antibody that targets specific genetic abnormalities in cancer cells, such as mismatch repair deficiency, which can lead to a high rate of tumor response. This approach is particularly novel for treating cancers like endometrial cancer and has shown promising results in clinical trials for other cancers, including rectal cancer. ^{10 11 12 13 14}

Research Team

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Eligibility Criteria

This trial is for young people with advanced solid tumors, including melanoma. It's looking to find the best dose of two drugs, Cobolimab and Dostarlimab, that children and young adults can tolerate.

Inclusion Criteria

I am 21 years old or younger and can sign the consent form.

My advanced cancer has worsened after treatment, and I have few treatment options left.

My blood tests show my organs are working well without recent medical help.

Exclusion Criteria

My cancer has spread to my brain and is not under control.

Participant has a heart rate-corrected QT interval according to QTcF prolongation at screening >470 msec or >480 msec for participants with bundle branch block

Has received treatment with an investigational agent within 21 days, or <5 times the half-life of the most recent therapy prior to study Day 1, whichever is shorter

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Determination

Participants receive varying doses of cobolimab and dostarlimab to determine the most tolerated dose

Approximately 21 days per cycle

Multiple visits per cycle

Dose Expansion

Participants receive the determined dose of cobolimab and dostarlimab to evaluate safety and efficacy

Up to approximately 46 months

Regular visits throughout the phase

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 70 months

Treatment Details

Interventions

• Cobolimab
• Dostarlimab

Trial Overview The study tests the combination of Cobolimab and Dostarlimab in pediatric and young adult patients. The aim is to determine a safe dosage level, manage side effects effectively, and assess how well these treatments work against cancer.

Participant Groups

Group I: Part 2- Dose expansion Experimental Treatment 2 Interventions

Group II: Part 1- Dose determination Experimental Treatment 2 Interventions

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

In a 24-week Phase 3 trial involving patients with psoriatic arthritis who had inadequate responses to previous treatments, risankizumab (RZB) significantly improved patient-reported outcomes, including pain, fatigue, and overall health-related quality of life compared to placebo.

Patients treated with RZB reported better scores in multiple health assessments, including the SF-36 and FACIT-Fatigue, indicating enhanced ability to perform daily activities and work, demonstrating its efficacy in managing symptoms of psoriatic arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved patient-reported outcomes in patients with psoriatic arthritis treated with risankizumab: analysis of the Phase 3 trial KEEPsAKE 2. Ostor, AJK., Soliman, AM., Papp, KA., et al.[2022]

In a study of 656 patients with rheumatoid arthritis, subcutaneous tocilizumab (TCZ-SC) administered every 2 weeks showed sustained efficacy over 2 years, with over 70% of patients maintaining an ACR 20 response throughout the study.

The safety profile of TCZ-SC was stable, with serious adverse events occurring at a rate of 11.20 per 100 patient-years, and no significant loss of efficacy was linked to the development of anti-TCZ antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-year Efficacy and Safety of Subcutaneous Tocilizumab in Combination with Disease-modifying Antirheumatic Drugs Including Escalation to Weekly Dosing in Rheumatoid Arthritis. Kivitz, A., Olech, E., Borofsky, MA., et al.[2019]

In a study involving 1681 patients with rheumatoid arthritis who had inadequate responses to previous treatments, tocilizumab showed rapid and sustained efficacy, with significant improvements in disease activity scores over 24 weeks.

The treatment was generally safe, with a low discontinuation rate of 5.1% due to adverse events, although patients who had recently used TNF inhibitors experienced a higher rate of adverse events compared to those who had never used them.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab in patients with active rheumatoid arthritis and inadequate responses to DMARDs and/or TNF inhibitors: a large, open-label study close to clinical practice. Bykerk, VP., Ostör, AJ., Alvaro-Gracia, J., et al.[2021]

Dostarlimab (JEMPERLI) has been shown to effectively reduce tumor size in patients with certain types of endometrial cancer, as demonstrated in the ongoing GARNET phase 1 clinical study.

The treatment was associated with manageable side effects and few severe adverse reactions, leading to its approval for patients with advanced or recurrent endometrial cancer, where treatment options are limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A plain language summary of results from the GARNET study of dostarlimab in patients with endometrial cancer. Oaknin, A., Gilbert, L., Tinker, AV., et al.[2023]

Tocilizumab 8 mg monotherapy was found to be the most effective treatment for achieving ACR20 response rates in rheumatoid arthritis patients who did not respond adequately to methotrexate, outperforming both sarilumab and adalimumab.

Sarilumab 200 mg was identified as potentially the safest option among the treatments studied, although there were no significant differences in serious adverse events across the different biologics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the efficacy and safety of tocilizumab, sarilumab, and sirukumab in comparison with adalimumab as monotherapy in patients with active rheumatoid arthritis: A Bayesian network meta-analysis of randomized controlled trials. Sung, YK., Lee, YH.[2021]

In a study of 40 patients with active Takayasu arteritis, adalimumab (ADA) showed a significantly higher efficacy rate at 6 months compared to tocilizumab (TCZ), with 85.71% of ADA patients responding positively versus 52.63% for TCZ (P=0.02).

Both treatments had similar relapse rates and adverse event incidences over 12 months, indicating that while ADA may be more effective, both therapies are comparably safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment efficacy and safety of adalimumab versus tocilizumab in patients with active and severe Takayasu arteritis: an open-label study. Wang, J., Kong, X., Ma, L., et al.[2023]

In a long-term safety analysis of ixekizumab involving 8228 patients over nearly 21,000 patient-years, the treatment showed a low incidence of serious adverse events, with rates for discontinuation due to adverse events at or below 5.1 per 100 patient-years.

The most common treatment-emergent adverse events were mild, such as nasopharyngitis and injection-site reactions, and the overall safety profile remained consistent with previous reports, indicating ixekizumab is well-tolerated over extended use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of ixekizumab in adult patients with plaque psoriasis, psoriatic arthritis and axial spondyloarthritis: data from 21 clinical trials. Genovese, MC., Mysler, E., Tomita, T., et al.[2021]

Guselkumab (GUS) demonstrated a favorable safety profile in patients with psoriatic arthritis (PsA), showing low adverse event (AE) rates for both TNFi-naïve (139.7/100 patient-years) and TNFi-experienced patients (174.0/100 patient-years) over a period of up to 2 years.

The safety outcomes, including rates of serious AEs and treatment discontinuation, were consistent between GUS-treated patients and those receiving placebo, indicating that GUS is a safe treatment option for PsA regardless of prior TNFi use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Guselkumab With and Without Prior Tumor Necrosis Factor Inhibitor Treatment: Pooled Results Across 4 Studies in Patients With Psoriatic Arthritis. Rahman, P., Boehncke, WH., Mease, PJ., et al.[2023]

The study aims to compare the safety and effectiveness of various classes of rheumatoid arthritis treatments, including older nonbiologic DMARDs, newer biologic DMARDs, and targeted synthetic therapies, in a real-world setting with a target enrollment of 2000 patients.

Conducted across 50 sites in Japan, the Corrona Japan RA Registry will gather comprehensive data on patient demographics, disease activity, and safety events, providing valuable insights into the performance of these therapies in everyday clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design characteristics of the Corrona Japan rheumatoid arthritis registry. Yamanaka, H., Kishimoto, M., Pappas, DA., et al.[2018]

Dostarlimab is approved for treating advanced endometrial cancer in patients with mismatch repair deficiency, highlighting its targeted approach to a specific genetic abnormality.

Aducanumab is indicated for Alzheimer's disease and received accelerated approval based on its ability to reduce amyloid beta plaques, although its clinical efficacy remains a topic of debate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Drug Update: Dostarlimab, Loncastuximab Tesirine, and Aducanumab. Gettman, L.[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 (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 showed promising antitumor activity in patients with recurrent/advanced non-small cell lung cancer (NSCLC) who had progressed after platinum-based chemotherapy, achieving an immune-related objective response rate (irORR) of 26.9% across various PD-L1 expression levels.

The treatment was generally well-tolerated, with fatigue being the most common severe adverse event (4.5%), and immune-related treatment-emergent adverse events occurring in 28.4% of patients, indicating an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Dostarlimab in Patients With Recurrent/Advanced Non-small Cell Lung Cancer: Results from Cohort E of the Phase I GARNET Trial. Moreno, V., Roda, D., Pikiel, J., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Improved patient-reported outcomes in patients with psoriatic arthritis treated with risankizumab: analysis of the Phase 3 trial KEEPsAKE 2. [2022]

2. Canada pubmed.ncbi.nlm.nih.gov

Two-year Efficacy and Safety of Subcutaneous Tocilizumab in Combination with Disease-modifying Antirheumatic Drugs Including Escalation to Weekly Dosing in Rheumatoid Arthritis. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Tocilizumab in patients with active rheumatoid arthritis and inadequate responses to DMARDs and/or TNF inhibitors: a large, open-label study close to clinical practice. [2021]

4. England pubmed.ncbi.nlm.nih.gov

A plain language summary of results from the GARNET study of dostarlimab in patients with endometrial cancer. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Comparison of the efficacy and safety of tocilizumab, sarilumab, and sirukumab in comparison with adalimumab as monotherapy in patients with active rheumatoid arthritis: A Bayesian network meta-analysis of randomized controlled trials. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Treatment efficacy and safety of adalimumab versus tocilizumab in patients with active and severe Takayasu arteritis: an open-label study. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Safety of ixekizumab in adult patients with plaque psoriasis, psoriatic arthritis and axial spondyloarthritis: data from 21 clinical trials. [2021]

8. Canada pubmed.ncbi.nlm.nih.gov

Safety of Guselkumab With and Without Prior Tumor Necrosis Factor Inhibitor Treatment: Pooled Results Across 4 Studies in Patients With Psoriatic Arthritis. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Design characteristics of the Corrona Japan rheumatoid arthritis registry. [2018]

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

New Drug Update: Dostarlimab, Loncastuximab Tesirine, and Aducanumab. [2022]

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

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

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

Dostarlimab: First Approval. [2021]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Dostarlimab: A Review. [2022]

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

Safety and Efficacy of Dostarlimab in Patients With Recurrent/Advanced Non-small Cell Lung Cancer: Results from Cohort E of the Phase I GARNET Trial. [2023]