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results
 
 

: PRELIMINARY RESULTS 

 
 
Safety and Efficacy Study of Pazopanib and Pembrolizumab 
 
(MK 3475)  in Advanced  Renal Cell Carcinoma (NCT02014636)
 
 
 Trial is still ongoing, but preliminary results were presented during ECC 2015 in September 2015

HOW MANY

people participated in the trial?

A total of 228 patients in 5 cancer centres in the USA and UK are expected to participate in phase I and phase II. Phase I is still ongoing but at the date of data cut-off (August 2015) 20 patients were enrolled in the trial.

STUDY

DESIGN

What did the study look like?

The trial will be done in two phases. Phase I is still ongoing but preliminary results were presented during ECC 2015. Phase II will be done in the future:

Phase I was conducted with only one study arm (group) for RCC patients: 20 patients were enrolled in the trial and received different dosages of pazopanib (VotrientTM) in combination with pembrolizumab (Keytruda™, MK-3475).

  • pazopanib (Votrient™) is an oral, small-molecule, multi-targeted receptor tyrosine kinase inhibitor, already approved for metastatic RCC
  • pembrolizumab (Keytruda™) is a fully human monoclonal antibody targeting PD-1 that is not yet approved for metastatic RCC

Participants received pazopanib orally and pembrolizumab intravenously in different dosages.

For further information on the design of the phase II trial please read here: Trial information pembrolizumab+pazopanib

RESULTS

of the study

Preliminary results of the phase I trial were presented in September 2015.
Phase I of the study aimed to answer the following questions:
  1. Is the combination of pazopanib and pembrolizumab safe and tolerable for patients with advanced renal cell carcinoma?
  2. How effective is the combination treatment for patients with advanced renal cell carcinoma?

The following could be observed:

1. Tolerability and side-effects:
All patients observed side-effects, most of them were moderate (up to grade 2). Most common side-effects (in more than 30% of the patients) were:
  • elevation of liver enzymes (ALT/AST)
  • diarrhea
  • fatigue
  • headache
  • nausea
  • arthralgia
  • vomiting
  • hypertension.

One patient in the dose-escalation cohort had a dose-limiting toxicity with grade 3 elevations of certain liver enzymes (ALT, AST, bilirubin and alkaline phosphatase). Liver enzymes are biomarkers for liver health, therefore high liver enzyme levels shows problems in liver function.

13 of the 20 patients had to stop treatment temporarily due to an increase of the liver enzymes ALT/AST (grade 3). All subsequently recovered with dose interruption/discontinuation plus corticosteroid-treatment.

After recovery from their first liver event, 12 of the 13 patients rejoined the study - first with pembrolizumab monotherapy, and 8 of whom also subsequently resumed pazopanib.

Liver enzymes remained normal during pembrolizumab monotherapy, however, following addition of pazopanib 6 of the 8 patients experienced recurrence of ALT/AST elevation again. They subsequently recovered with dose interruption/discontinuation and corticosteroid-treatment.

Dose-escalation of the combination of pazopanib plus pembrolizumab showed siginificant hepatotoxicity (liver problems).

2. Efficacy:
The confirmed overall response rate was 60% in the group of patients that received 800mg pazopanib plus pembrolizumab and 20% in the pazopanib 600mg plus pembrolizumab group.

One patient treated with 800mg pazopanib plus pembrolizumab experienced a complete response (meaning that there is no evidence of disease anymore).

CONCLUSION

 

Preliminary results of the combination of pazopanib plus pembrolizumab for the treatment of patients with advanced kidney cancer showed significant hepatotoxicity (liver problems), but that these seemed to only be due to the pazopanib.

As preliminary evidence of antitumor activity was observed, new dosing schemes including sequential use of these agents will be explored in the future.

Summary poster of this trial as presented can be found here: pdf Download of ECC poster (96 KB)

SHARE

your experience 

Were you one of the patients on this trial? Do you want to share your experience with other patients? Please send us an e-mail to:This email address is being protected from spambots. You need JavaScript enabled to view it.

Note that your experience would be helpful for other patients and patient organisations. However, your information will not be released to any patient group or anyone outside of the IKCC Board without your explicit permission to do so. For details on our privacy policy, click here.

Disclaimer: This is a patient-friendly summary of the results of this clinical trial which has been medically reviewed, but is provided for informational purposes only.
 
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