FDA News

FDA grants Braftovi-Mektovi plus Erbitux breakthrough therapy designation for colorectal cancer

The FDA granted breakthrough therapy designation to the combination of encorafenib, binimetinib and cetuximab for the treatment of patients with BRAF V600E-mutant metastatic colorectal cancer following the failure of one or two prior lines of therapy, according to the manufacturer.

The FDA approved the combination of encorafenib (Braftovi, Array BioPharma) — a BRAF inhibitor — and binimetinib (Mektovi, Array BioPharma), a MEK inhibitor, for the treatment of BRAF-mutated melanoma in June.

Cetuximab (Erbitux, Eli Lilly) — an EGFR inhibitor — is indicated for the treatment of certain patients with KRAS wild-type, EGFR-expressing, metastatic colorectal cancer.

“We are delighted that the FDA has recognized the potential of this combination for patients with BRAF V600E-mutant metastatic colorectal cancer,” Victor Sandor, MD, chief medical officer at Array Biopharma, said in a press release. “As there are no regimens approved specifically for BRAF V600E-mutant metastatic colorectal cancer, this designation provides us with the opportunity to work closely with the FDA to potentially accelerate our effort to bring an important treatment option to these patients in critical need.”

The FDA based the breakthrough therapy designation for the combination of encorafenib plus binimetinib and cetuximab on data from the safety lead-in of the ongoing randomized phase 3 BEACON CRC trial. Researchers presented data from the trial at the ESMO World Congress on Gastrointestinal Cancer in June.

During the safety lead-in, 30 patients with metastatic colorectal cancer received encorafenib plus binimetinib and cetuximab. Twenty-nine of the patients had BRAF V600E mutant tumors.

Results showed fully mature OS data through 12.6 months. Median OS had not been reached at the time of analysis.

Sixty-two percent of the safety lead-in cohort achieved 1-year OS. Median PFS was 8 months (95% CI, 5.6-9.3).

Researchers observed an overall response rate of 48% (n = 17) in the total cohort and 62% among those treated with only one prior line of therapy.

The triplet combination appeared well tolerated. The most common grade 3 or grade 4 adverse events included fatigue (13%), anemia (10%), increased blood creatine kinase (10%) and increased aspartate aminotransferase (10%).

Results from the safety lead-in prompted the initiation of the randomized portion of the BEACON CRC trial.

The open-label, global trial will enroll about 615 patients across 200 investigational sites to assess the safety and efficacy of the triplet combination. Researchers will randomly assign patients 1:1:1 to triplet combination, doublet combination with encorafenib and binimetinib, or irinotecan-based therapy with cetuximab. OS will serve as the primary endpoint.

Investigators expect enrollment to complete at the end of year.

The FDA granted breakthrough therapy designation to the combination of encorafenib, binimetinib and cetuximab for the treatment of patients with BRAF V600E-mutant metastatic colorectal cancer following the failure of one or two prior lines of therapy, according to the manufacturer.

The FDA approved the combination of encorafenib (Braftovi, Array BioPharma) — a BRAF inhibitor — and binimetinib (Mektovi, Array BioPharma), a MEK inhibitor, for the treatment of BRAF-mutated melanoma in June.

Cetuximab (Erbitux, Eli Lilly) — an EGFR inhibitor — is indicated for the treatment of certain patients with KRAS wild-type, EGFR-expressing, metastatic colorectal cancer.

“We are delighted that the FDA has recognized the potential of this combination for patients with BRAF V600E-mutant metastatic colorectal cancer,” Victor Sandor, MD, chief medical officer at Array Biopharma, said in a press release. “As there are no regimens approved specifically for BRAF V600E-mutant metastatic colorectal cancer, this designation provides us with the opportunity to work closely with the FDA to potentially accelerate our effort to bring an important treatment option to these patients in critical need.”

The FDA based the breakthrough therapy designation for the combination of encorafenib plus binimetinib and cetuximab on data from the safety lead-in of the ongoing randomized phase 3 BEACON CRC trial. Researchers presented data from the trial at the ESMO World Congress on Gastrointestinal Cancer in June.

During the safety lead-in, 30 patients with metastatic colorectal cancer received encorafenib plus binimetinib and cetuximab. Twenty-nine of the patients had BRAF V600E mutant tumors.

Results showed fully mature OS data through 12.6 months. Median OS had not been reached at the time of analysis.

Sixty-two percent of the safety lead-in cohort achieved 1-year OS. Median PFS was 8 months (95% CI, 5.6-9.3).

Researchers observed an overall response rate of 48% (n = 17) in the total cohort and 62% among those treated with only one prior line of therapy.

The triplet combination appeared well tolerated. The most common grade 3 or grade 4 adverse events included fatigue (13%), anemia (10%), increased blood creatine kinase (10%) and increased aspartate aminotransferase (10%).

Results from the safety lead-in prompted the initiation of the randomized portion of the BEACON CRC trial.

The open-label, global trial will enroll about 615 patients across 200 investigational sites to assess the safety and efficacy of the triplet combination. Researchers will randomly assign patients 1:1:1 to triplet combination, doublet combination with encorafenib and binimetinib, or irinotecan-based therapy with cetuximab. OS will serve as the primary endpoint.

Investigators expect enrollment to complete at the end of year.