Cobolimab + Dostarlimab for Cancer

Not currently recruiting at 40 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two experimental cancer treatments, cobolimab and dostarlimab, to determine the optimal dose and effectiveness in children and young adults with advanced solid tumors. Researchers aim to assess the safety of these treatments and manage any side effects. The trial seeks participants with specific cancers, such as melanoma and Hodgkin lymphoma, who have limited treatment options or specific circumstances, like previous treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive these new treatments.

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.

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

Studies have shown that using cobolimab and dostarlimab together is generally safe for patients. Research indicates that people with non-small cell lung cancer tolerated this combination well. Although patients experienced some side effects, they were manageable. Initial results also show that this treatment combination has an acceptable safety profile and can help fight tumors. In another study, the combination improved response rates in melanoma, a type of skin cancer, and was found to be tolerable. Overall, these findings suggest the treatment is safe enough for further testing, especially in children and young adults with advanced solid tumors. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Cobolimab and Dostarlimab for cancer because these treatments target the immune system in novel ways. Unlike traditional chemotherapy, which attacks cancer cells directly, these drugs work by boosting the body's own immune response to recognize and destroy cancer cells. Cobolimab blocks a protein called TIM-3, potentially enhancing the immune attack on cancer cells. Dostarlimab, on the other hand, is a type of immunotherapy known as a PD-1 inhibitor, which helps the immune system stay active longer against cancer. This dual approach could offer a more targeted and effective option with possibly fewer side effects compared to standard treatments.

What evidence suggests that cobolimab and dostarlimab could be effective for advanced solid tumors?

This trial will evaluate the combination of cobolimab and dostarlimab for cancer treatment. Studies have shown that using cobolimab with dostarlimab can help treat certain cancers. Research indicates that this combination improves the body's response to treatment and reduces the chance of cancer returning in patients with high-risk melanoma. Early results suggest that this treatment is generally safe and active against tumors in advanced cases. Additionally, patients with non-small cell lung cancer (NSCLC) showed early signs of effectiveness and safety with this treatment. Overall, the combination of cobolimab and dostarlimab shows promise in improving outcomes for various cancers. ^{2 3 6 7 8}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Are You a Good Fit for This Trial?

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 Hodgkin lymphoma has not improved after two treatments.

Exclusion Criteria

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

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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]

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 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 (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 (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]

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]

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]

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]

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]

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]

Citations

1. onclive.com onclive.com/view/dostarlimab-plus-cobolimab-improves-mpr-rate-vs-dostarlimab-in-high-risk-resectable-melanoma

Dostarlimab Plus Cobolimab Improves MPR Rate vs ... Dostarlimab plus cobolimab bested dostarlimab monotherapy in terms of MPR and RFS in patients with high-risk resectable melanoma.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.4099

Cobolimab and dostarlimab in the first-line treatment of ... Cobolimab plus dostarlimab yielded promising response rates and survival outcomes with acceptable safety as first-line treatment in patients with CP A, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12351273/

Combined Targeting of PD-1 and TIM-3 in Patients with ... Initial results demonstrated that cobolimab in combination with dostarlimab had an acceptable safety profile and was associated with antitumor activity in ...

4. jitc.bmj.com jitc.bmj.com/content/11/Suppl_1/A678

596 AMBER, Part 2B: a phase 1 study of cobolimab plus ... Conclusions Cobolimab plus dostarlimab showed early evidence of efficacy and acceptable safety in patients with advanced/metastatic NSCLC.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04655976

NCT04655976 | Efficacy Comparison of Cobolimab ... This is a multi-center, parallel group treatment, Phase 2/3 open label study evaluating cobolimab in combination with dostarlimab and docetaxel in ...

6. onclive.com onclive.com/view/cobolimab-dostarlimab-combination-shows-initial-efficacy-and-safety-signals-in-advanced-nsclc

Cobolimab/Dostarlimab Combination Shows Initial Efficacy ... Cobolimab plus dostarlimab-gxly showed activity and acceptable safety across all dose levels assessed in patients with non–small cell lung cancer.

7. targetedonc.com targetedonc.com/view/cobolimab-dostarlimab-combo-improves-responses-in-high-risk-melanoma

Cobolimab/Dostarlimab Combo Improves Responses in ... Adding cobolimab to dostarlimab as neoadjuvant treatment for high-risk resectable melanoma improved major pathological response rates and was tolerable.

8. asco.org asco.org/abstracts-presentations/ABSTRACT371142

AMBER parts 1c and 1e: A phase 1 study of cobolimab ... An integrated safety analysis for all pts (Parts 1 and 2) receiving cobolimab with dostarlimab, regardless of tumor type or cobolimab dose, is reported here.