110 Participants Needed

PT2385 for Kidney Cancer

Recruiting at 24 trial locations
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

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 participate if you are on warfarin or have certain medical conditions. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug PT2385/MK-3795 for kidney cancer?

The combination of cabozantinib (Cabometyx) and nivolumab (Opdivo) has been shown to be effective for advanced kidney cancer, with studies indicating longer survival and better quality of life compared to other treatments. This combination is recommended as a first-line treatment for advanced renal cell carcinoma.12345

What safety information is available for PT2385/MK-3795 (Cabozantinib and Nivolumab) in kidney cancer treatment?

The combination of cabozantinib and nivolumab has been studied for safety in treating advanced kidney cancer. While the safety profile is generally manageable, some side effects like diarrhea, liver issues, skin reactions, fatigue, and kidney problems can occur. These side effects can often be managed with supportive care and dose adjustments.12678

How is the drug PT2385/MK-3795 for kidney cancer different from other treatments?

The drug PT2385/MK-3795 is unique because it combines cabozantinib, which targets multiple pathways involved in kidney cancer growth, with nivolumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells. This combination aims to enhance treatment effectiveness by targeting cancer from different angles, which is different from using a single type of drug.1291011

What is the purpose of this trial?

PART 1: The primary objective of this study is to identify the maximum tolerated dose (MTD) of MK-3795, formerly called PT2385 and/or the recommended Phase 2 dose (RP2D) of MK-3795 in patients with advanced clear cell renal cell carcinoma (ccRCC).PART 2: The primary objective of this study is to identify the MTD of MK-3795 up to the RP2D, in combination with nivolumab, in patients with advanced ccRCC.As of Amendment 09 (29 Mar 2024), participants with advanced ccRCC will transition from MK-3795 to belzutifan (MK-6482) in combination with nivolumab or belzutifan alone.PART 3: The primary objective of this study is to identify the MTD of MK-3795 up to the RP2D, in combination with cabozantinib tablets, in patients with advanced ccRCC.

Research Team

MD

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults over 18 with advanced clear cell renal cell carcinoma who've had at least one prior treatment but no more than three, including a specific type of drug targeting blood vessel growth. They must expect to live at least 3 months, be able to take pills, and use approved birth control if necessary. Exclusions include recent major surgery, other clinical trials participation, untreated brain metastases, uncontrolled hypertension, certain heart conditions within the past 6 months.

Inclusion Criteria

My kidney cancer has spread and worsened despite treatment.
I've had 3 or fewer treatments for my advanced cancer.
I have had 1 or 2 treatments targeting blood vessel growth in my cancer.
See 5 more

Exclusion Criteria

I have untreated brain metastasis or a history of leptomeningeal disease or spinal cord compression.
I still have side effects from previous cancer treatments.
I am currently being treated for an infection.
See 11 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants receive MK-3795 at escalating doses to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D).

Up to 1 year
Frequent visits for safety monitoring and dose escalation

Treatment Part 2

Participants receive MK-3795 in combination with nivolumab, transitioning to belzutifan with or without nivolumab as per protocol amendment.

Up to 1 year
Every 2 weeks for nivolumab infusion

Treatment Part 3

Participants receive MK-3795 in combination with cabozantinib to determine the MTD and RP2D.

Up to 1 year
Regular visits for safety monitoring and dose adjustments

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Up to 9 years

Treatment Details

Interventions

  • Cabozantinib
  • Nivolumab
  • PT2385/MK-3795
Trial Overview The study tests different doses of MK-3795 alone and in combination with Nivolumab or Cabozantinib to find the highest dose patients can tolerate without severe side effects (MTD) and recommend for future studies (RP2D). It's divided into three parts: testing MK-3795 alone; then with Nivolumab; and finally with Cabozantinib.
Participant Groups
3Treatment groups
Experimental Treatment
Group I: Part 3: MK-3795 + CabozantinibExperimental Treatment2 Interventions
Participants with advanced ccRCC in the expansion phase receive the RP2D of MK-3795 in combination with cabozantinib 20mg up to 60mg orally QD for up to approximately 1 year (12 cycles; each cycle length = 28 days) or until unequivocal progression or treatment discontinuation, whichever occurs later.
Group II: Part 2: MK-3795 + Nivolumab + BelzutifanExperimental Treatment3 Interventions
Participants with advanced ccRCC in the expansion phase receive the RP2D of MK-3795 orally in combination with nivolumab 240mg by IV infusion over \~60 minutes every 2 weeks for up to \~1 year (12 cycles; each cycle length = 28 days) or until unequivocal progression or treatment discontinuation, whichever occurs later. As per Amendment 09 (29 March 2024), participants will not receive MK-3795. Participants receive nivolumab 240mg by IV infusion over \~60 minutes every 2 weeks in combination with belzutifan 120 mg once daily (QD) for up to \~1 year (12 cycles; each cycle length = 28 days) or until unequivocal progression or treatment discontinuation, whichever occurs later. If participants experience an adverse event, then nivolumab will be discontinued and participants will continue to receive belzutifan 120 mg QD alone for up to \~1 year (12 cycles; each cycle length = 28 days) or until unequivocal progression or treatment discontinuation, whichever occurs later.
Group III: Part 1: MK-3795Experimental Treatment1 Intervention
Participants with advanced ccRCC receive MK-3795 at an initial dose level of 100mg orally, twice daily (BID) up to approximately 3 weeks. Dose levels will be escalated to identify the maximum tolerated dose (MTD) and/or Recommended Phase 2 Dose (RP2D) for MK-3795. Each escalated dose will be continued for up to approximately 3 weeks before escalating a dose again until a dose limiting toxicity (DLT) is experienced. Thereafter, participants receive RP2D dose of MK-3795 for up to 2 cycles (each cycle length = 28 days) for up to approximately 1 year. Participants may continue to receive MK-3795 beyond 1 year at the discretion of the Sponsor.

Cabozantinib is already approved in European Union, United States, Canada, Japan for the following indications:

🇪🇺
Approved in European Union as Cabometyx for:
  • Renal cell carcinoma
  • Hepatocellular carcinoma
🇺🇸
Approved in United States as Cabometyx for:
  • Renal cell carcinoma
  • Hepatocellular carcinoma
🇨🇦
Approved in Canada as Cabometyx for:
  • Renal cell carcinoma
  • Hepatocellular carcinoma
🇯🇵
Approved in Japan as Cabometyx for:
  • Renal cell carcinoma

Find a Clinic Near You

Who Is Running the Clinical Trial?

Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

Lead Sponsor

Trials
8
Recruited
460+

Peloton Therapeutics, Inc.

Lead Sponsor

Trials
8
Recruited
460+

Findings from Research

In a phase 3 trial involving 855 patients with untreated advanced renal-cell carcinoma, the combination of cabozantinib with nivolumab and ipilimumab significantly improved progression-free survival compared to nivolumab and ipilimumab alone, with a 12-month progression-free survival rate of 57% versus 49%.
However, the experimental group experienced a higher incidence of severe adverse events (grade 3 or 4) at 79%, compared to 56% in the control group, indicating a trade-off between efficacy and safety.
Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma.Choueiri, TK., Powles, T., Albiges, L., et al.[2023]
In a phase II trial involving 47 patients with advanced non-clear-cell renal cell carcinoma, the combination of cabozantinib and nivolumab showed a promising objective response rate of 47.5% in patients with papillary, unclassified, or translocation-associated RCC, along with a median progression-free survival of 12.5 months.
The treatment was less effective in chromophobe RCC, with no objective responses observed, highlighting the need for further research into genomic predictors of response, particularly mutations like NF2 and FH that were associated with better outcomes.
Phase II Trial of Cabozantinib Plus Nivolumab in Patients With Non-Clear-Cell Renal Cell Carcinoma and Genomic Correlates.Lee, CH., Voss, MH., Carlo, MI., et al.[2023]
The combination of cabozantinib (a TKI) and nivolumab (an anti-PD-1 antibody) is an effective first-line treatment for previously-untreated advanced renal cell carcinoma (RCC), showing significantly longer progression-free and overall survival compared to sunitinib monotherapy in the CheckMate 9ER trial.
Patients receiving cabozantinib plus nivolumab reported better health-related quality of life, although the combination therapy had a higher incidence of serious adverse events compared to sunitinib, indicating a need for careful monitoring.
Cabozantinib plus Nivolumab: A Review in Advanced Renal Cell Carcinoma.Markham, A.[2022]

References

Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma. [2023]
Phase II Trial of Cabozantinib Plus Nivolumab in Patients With Non-Clear-Cell Renal Cell Carcinoma and Genomic Correlates. [2023]
Cabozantinib plus Nivolumab: A Review in Advanced Renal Cell Carcinoma. [2022]
Complete response of metastatic papillary renal cell carcinoma with inferior vena cava tumor thrombus to nivolumab plus cabozantinib. [2023]
European Association of Urology Guidelines for Clear Cell Renal Cancers That Are Resistant to Vascular Endothelial Growth Factor Receptor-Targeted Therapy. [2018]
Management of adverse events associated with cabozantinib plus nivolumab in renal cell carcinoma: A review. [2023]
Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. [2022]
Adverse Events of Cabozantinib Plus Nivolumab Versus Ipilimumab Plus Nivolumab. [2023]
CaboPoint: a phase II study of cabozantinib as second-line treatment in patients with metastatic renal cell carcinoma. [2022]
Cabozantinib as first-line treatment in advanced renal cell carcinoma: a profile of its use. [2020]
11.United Statespubmed.ncbi.nlm.nih.gov
Cabozantinib as a novel therapy for renal cell carcinoma. [2022]
Unbiased ResultsWe believe in providing patients with all the options.
Your Data Stays Your DataWe only share your information with the clinical trials you're trying to access.
Verified Trials OnlyAll of our trials are run by licensed doctors, researchers, and healthcare companies.
Back to top
Terms of Service·Privacy Policy·Cookies·Security