GME751 vs Keytruda for Melanoma

Recruiting at 41 trial locations

Overseen By Clinical Disclosure Representative

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Sandoz

Must be taking: Pembrolizumab

Must not be taking: Live vaccines, Anti-PD-1 agents

Disqualifiers: Ocular melanoma, Autoimmune disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

318 Participants Needed

Trial Summary

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 last 2 years, you may not be eligible to participate.

What data supports the effectiveness of the drug Keytruda for treating melanoma?

Keytruda (pembrolizumab) has been shown to be effective in treating advanced melanoma, with studies indicating it can improve survival rates and reduce tumor size in patients. In clinical trials, it demonstrated significant benefits in terms of progression-free survival and overall response rates compared to other treatments. ^{1 2 3 4 5}

What is the safety profile of Keytruda (pembrolizumab) for melanoma?

Keytruda (pembrolizumab) has been studied for safety in melanoma patients, with common side effects including fatigue, cough, nausea, itching, rash, decreased appetite, constipation, joint pain, and diarrhea. Some patients experienced immune-related side effects like lung inflammation, colon inflammation, liver inflammation, pituitary gland inflammation, and thyroid issues. ^{1 6 7 8 9}

How does the drug GME751 differ from Keytruda for treating melanoma?

GME751 is being compared to Keytruda, a well-established drug for advanced melanoma that works by blocking a protein called PD-1, which helps the immune system attack cancer cells. The unique aspect of GME751 in this trial is its potential to offer a different mechanism of action or improved outcomes compared to Keytruda, although specific details about GME751's mechanism or benefits are not provided in the available research. ^{1 3 6 10 11}

What is the purpose of this trial?

The purpose of this study is to investigate the pharmacokinetic (PK) similarity and efficacy, safety, and immunogenicity of GME751 compared with Keytruda® (pembrolizumab) in subjects with resected advanced melanoma requiring adjuvant treatment with pembrolizumab.

Eligibility Criteria

Adults diagnosed with advanced melanoma that's been surgically removed within the past 13 weeks can join. They should be in good health with a performance status of 0 or 1, indicating they're fully active or have some symptoms but don't need bed rest. People with eye-related melanoma, severe allergies to pembrolizumab, autoimmune diseases, recent live vaccines, or prior treatments targeting T cell receptors cannot participate.

Inclusion Criteria

I am fully active or have some restrictions but can still care for myself.

My organs are working well.

I have been diagnosed with advanced melanoma.

Exclusion Criteria

I have a history of eye melanoma.

Known history of hypersensitivity (grade ≥3) to pembrolizumab or its excipients

I have not received a live vaccine in the last 30 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive either GME751, Keytruda-US, or Keytruda-EU for 24 weeks in 4 treatment cycles, each of 6 weeks duration

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants benefiting from treatment without signs of recurrence or unacceptable toxicity may continue pembrolizumab treatment based on country regulations

Treatment Details

Interventions

• GME751
• Keytruda

Trial Overview The trial is testing GME751 against US-licensed and EU-authorized Keytruda (both forms of pembrolizumab) for their effects on drug levels in the body and overall safety and effectiveness in preventing melanoma from returning after surgery.

Participant Groups

Group I: GME751 Experimental Treatment 1 Intervention

Subjects will receive GME751 via intravenous (IV) infusion.

Group II: Keytruda - US Active Control 1 Intervention

Subjects will receive Keytruda-US via intravenous (IV) infusion.

Group III: Keytruda - EU Active Control 1 Intervention

Subjects will receive Keytruda-EU via intravenous (IV) infusion.

Who Is Running the Clinical Trial?

Sandoz

Lead Sponsor

Trials

145

Recruited

26,800+

Dr. David Chang

Sandoz

Chief Medical Officer

MD from Albert Einstein College of Medicine

Richard Saynor

Sandoz

Chief Executive Officer since 2019

Bachelor of Pharmacy from the University of Bradford

Findings from Research

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Nivolumab combined with ipilimumab demonstrated significantly better overall survival compared to BRAF + MEK inhibitors, with hazard ratios indicating a 36% to 44% reduction in the risk of death after 12 months.

While nivolumab + ipilimumab had improved survival outcomes, it also resulted in a higher rate of grade 3/4 adverse events (54.1%) compared to dabrafenib + trametinib (31.6%) and similar rates to vemurafenib + cobimetinib (59.5%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy of combination immunotherapy and targeted therapy in the treatment of BRAF-mutant advanced melanoma: a matching-adjusted indirect comparison. Atkins, MB., Tarhini, A., Rael, M., et al.[2020]

Pembrolizumab (Keytruda) is an effective treatment for advanced melanoma, showing significant improvements in progression-free survival and overall response rates compared to ipilimumab and chemotherapy in clinical trials involving patients with varying treatment histories.

The drug has a manageable safety profile, with immune-related side effects that are generally reversible, making it a valuable option for patients who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: A Review in Advanced Melanoma. Deeks, ED.[2022]

In a study of 168 patients with advanced melanoma treated with pembrolizumab in community oncology settings, the median overall survival was 19.4 months, indicating its effectiveness in real-world scenarios.

Treatment-related toxicity led to discontinuation in 25% of patients, highlighting the importance of monitoring side effects, although the safety profile of pembrolizumab aligns with clinical trial results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Utilization and Outcomes for Advanced Melanoma in US Community Oncology Practices. Cowey, CL., Liu, FX., Black-Shinn, J., et al.[2021]

In a study of 655 patients with advanced melanoma, pembrolizumab showed a 5-year overall survival rate of 34%, with even better outcomes (41%) for treatment-naive patients, indicating its long-term efficacy.

The treatment was generally well-tolerated, with 86% of patients experiencing treatment-related adverse events, but only 7.8% discontinued due to these effects, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Hamid, O., Robert, C., Daud, A., et al.[2023]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In the phase III CheckMate 238 trial, 67.7% of patients receiving nivolumab experienced treatment-related adverse events (TRAEs), with the most common being pruritus and diarrhea, primarily occurring within the first 3 months of treatment.

Despite the high incidence of TRAEs, there was no significant association found between these adverse events and recurrence-free survival (RFS), indicating that the safety profile of nivolumab remains consistent and does not negatively impact long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant nivolumab for stage III/IV melanoma: evaluation of safety outcomes and association with recurrence-free survival. Mandala, M., Larkin, J., Ascierto, PA., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

In a study of 576 patients with advanced melanoma receiving nivolumab, 71% experienced treatment-related adverse events (AEs), primarily low-grade, with fatigue, pruritus, diarrhea, and rash being the most common, and no drug-related deaths reported.

Patients who experienced any grade of treatment-related select AEs had a significantly higher objective response rate (ORR), indicating a potential link between these AEs and improved treatment efficacy, although the use of immune-modulating agents to manage AEs did not impact ORR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Profile of Nivolumab Monotherapy: A Pooled Analysis of Patients With Advanced Melanoma. Weber, JS., Hodi, FS., Wolchok, JD., et al.[2022]

Pembrolizumab (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

In a meta-analysis of 15 studies involving cancer patients treated with either nivolumab or pembrolizumab, nivolumab was associated with a higher overall incidence of cardiotoxicity (55.7%) compared to pembrolizumab (27.31%), although this difference was not statistically significant.

However, when looking specifically at myocarditis, pembrolizumab showed a significant increase in cardiotoxicity risk, suggesting that while nivolumab may be more commonly reported for general cardiotoxicity, pembrolizumab poses a greater risk for this specific heart condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative cardiotoxicity risk of pembrolizumab versus nivolumab in cancer patients undergoing immune checkpoint inhibitor therapy: A meta-analysis. Ndjana Lessomo, FY., Wang, Z., Mukuka, C.[2023]

References

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Comparative efficacy of combination immunotherapy and targeted therapy in the treatment of BRAF-mutant advanced melanoma: a matching-adjusted indirect comparison. [2020]

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

Pembrolizumab: A Review in Advanced Melanoma. [2022]

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

Pembrolizumab Utilization and Outcomes for Advanced Melanoma in US Community Oncology Practices. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. [2023]

6. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

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

Adjuvant nivolumab for stage III/IV melanoma: evaluation of safety outcomes and association with recurrence-free survival. [2022]

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

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

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

Safety Profile of Nivolumab Monotherapy: A Pooled Analysis of Patients With Advanced Melanoma. [2022]

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

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Comparative cardiotoxicity risk of pembrolizumab versus nivolumab in cancer patients undergoing immune checkpoint inhibitor therapy: A meta-analysis. [2023]