Study of Efficacy and Safety of Novel Spartalizumab Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma — PLATforM  

Melanoma Clinical Trial

Official title: A Randomized, Open-label, Phase II Open Platform Study Evaluating the Efficacy and Safety of Novel Spartalizumab (PDR001) Combinations in Previously Treated Unresectable or Metastatic Melanoma

Status Completed

Clinical Trial Summary

The primary purpose of this study is to evaluate the efficacy of novel spartalizumab (PDR001) combinations in previously treated unresectable or metastatic melanoma

Clinical Trial Description

This study was a randomized, open-label, two-part, multi-center, open platform phase II study designed to evaluate the efficacy and safety of the anti-PD-1 antibody PDR001 in combination with novel agents for previously treated unresectable or metastatic melanoma. Additionally, a non-randomized single-arm was added based on interim analysis findings to assess the efficacy and safety of PDR001 in combination with LAG525 in subjects with previously treated unresectable or metastatic LAG-3 positive melanoma.

The study consisted of two parts: the selection part and the expansion part, which were applicable to both the randomized and non-randomized sections. In the randomized section, participants were randomized to one of four combination arms available for enrollment:

• Arm 1: LAG525 600 mg intravenously (i.v.) every 4 weeks (Q4W) and PDR001 400 mg i.v. Q4W.

• Arm 2: INC280 400 mg orally (p.o.) twice daily (BID) and PDR001 400 mg i.v. Q4W.

• Arm 3: ACZ885 300 mg subcutaneously (s.c.) every 4 weeks (Q4W) and PDR001 400 mg i.v. Q4W.

• Arm 4: LEE011 600 mg p.o. once daily (QD) on Days 1-21 of a 28-day cycle and PDR001 400 mg i.v. Q4W.

At each interim analysis, the following determinations were made: (1) which arm met the pre-specified efficacy criteria and expanded to the expansion part, (2) which arms continued enrollment in selection part (up to 45 subjects), and (3) which arms were discontinued due to futility, considering efficacy, safety, and biomarker data. The expansion phase included enrollment of subjects only in the combination arms that met the pre-specified criteria in selection part.

In the non-randomized section, a single combination arm was opened for enrollment in selection part:

• Arm 1A: LAG525 600 mg i.v. Q4W and PDR001 400 mg i.v. Q4W, assessed in a population selected based on the LAG-3 status of their tumor.

Arm 1A would be eligible for enrollment in expansion part only if it met the pre-specified criterion for this arm.

Participants received the study treatment corresponding to their assigned arm on a 28-day cycle basis until disease progression, as determined by local assessment using RECIST v1.1 criteria, or until certain events occurred, such as unacceptable toxicity, initiation of subsequent anti-cancer therapy, withdrawal of consent, investigator's decision, loss to follow-up, death, or termination of the study by the sponsor. Following discontinuation of the study treatment, all subjects were monitored for safety evaluations for up to 150 days after their last dose of the study treatment. ;

Related Conditions & MeSH terms

• Melanoma

• NCT number: NCT03484923
• Study type: Interventional
• Source: Novartis
• Status: Completed
• Phase: Phase 2
• Start date: September 10, 2018
• Completion date: December 30, 2022