Phase 3 COMBI-i Study Fails to Meet Primary End Point of PFS


The study was evaluating spartalizumab in combination with dabrafenib and trametinib among untreated patients with stage IIIC or stage IV BRAFV600 mutation-positive cutaneous melanoma.

The phase 3 COMBI-i study, evaluating spartalizumab (PDR001) in combination with dabrafenib (Tafinlar) and trametinib (Mekinist), did not meet its primary end point of investigator-assessed progression-free survival (PFS), according to Novartis, the developer of spartalizumab.1

The trial was specifically conducted among untreated patients with stage IIIC or stage IV BRAFV600 mutation-positive cutaneous melanoma, compared to the combination of placebo with dabrafenib and trametinib alone.

“While the COMBI-i trial did not reach its primary endpoint, the study’s findings give us valuable insights into the role the investigational immunotherapy spartalizumab may play in future cancer therapy combinations and underscore the previously established importance of [dabrafenib plus trametinib] for these patients,” John Tsai, MD, head of Global Drug Development and chief medical officer at Novartis, said in a press release. “Novartis remains committed to melanoma patients through ongoing research, and we continue to deliver the approved combination therapy [dabrafenib plus trametinib] to patients around the world.”

“We extend our gratitude to the patients and investigators who participated in the COMBI-i study,” Tsai continued. “Their partnership has expanded our understanding of spartalizumab and its potential role in future cancer treatments.”

The randomized, double-blind, placebo-controlled, phase 3 COMBI-i trial was conducted in 3 parts. The current results are from part 3 of the trial.

Novartis indicated that it will continue to review the data along with the COMBI-i study investigators to learn more from the results, which are expected to be submitted for presentation at an upcoming medical meeting. In addition, the company suggested that it will continue the development program of spartalizumab, investigating the immunotherapy across a range of tumor types.

Dabrafenib plus trametinib remains an effective treatment options based on previously reported data from large, phase 3 clinical trials. Most recently, results from a 5-year analysis of the COMBI-AD study, presented at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program, confirmed the long-term benefit of adjuvant dabrafenib in patients with resected stage III BRAFv600-mutant melanoma.2


1. Novartis provides update on Phase III study evaluating investigational spartalizumab (PDR001) in combination with Tafinlar® + Mekinist® in advanced melanoma [news release]. Basel. Published August 22, 2020. Accessed August 24, 2020.

2. Hauschild A, Dummer R, Santinami M, et al. Long-term benefit of adjuvant dabrafenib + trametinib (D+T) in patients (pts) with resected stage III BRAF V600–mutant melanoma: Five-year analysis of COMBI-AD. Presented at the 2020 ASCO Virtual Scientific Program. Abstract #: 10001.

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