Efficacy

Study Designs

Across tumor types, TAFINLAR + MEKINIST was evaluated in patients with BRAF V600E–mutant solid tumors.

TAFINLAR + MEKINIST was evaluated in BRAF V600E–mutant solid tumors based on collective evidence from 2 adult trials and 2 pediatric trials (see study design details below), and is supported by the results of COMBI-d, COMBI-v, and BRF113928 studies.^1,2

Adult Studies

ROAR (BRF117019) Study

TAFINLAR + MEKINIST was evaluated in a multicohort, multicenter, nonrandomized, open-label trial in adult patients with selected tumors with the BRAF V600E mutation, including high-grade glioma (HGG) (n=45), biliary tract cancer (BTC) (n=43), low-grade glioma (LGG) (n=13), adenocarcinoma of small intestine (n=3), gastrointestinal stromal tumor (n=1), and anaplastic thyroid cancer (n=36). Patients were enrolled based on local assessments of BRAF V600E mutation status; a central laboratory confirmed the BRAF mutation in 93 of 105 patients.^1,2

NCI-MATCH (EAY131-H) Study

TAFINLAR + MEKINIST was evaluated in Arm H (EAY131-H) of the NCI-MATCH Study, a single-arm, open-label study that enrolled patients with a BRAF V600E mutation. Patients with melanoma, thyroid cancer, or colorectal cancer were excluded. BRAF V600E mutation status for enrollment was determined either by central or local laboratory test. The study included adult patients with solid tumors including gastrointestinal tumors (n=14), lung tumors (n=7), gynecologic or peritoneal tumors (n=6), central nervous system tumors (n=4), and ameloblastoma of mandible (n=1).^1,2

In both adult studies, patients received TAFINLAR 150 mg twice daily and MEKINIST 2 mg once daily. The major efficacy outcome measures were overall response rate (ORR) per Response Evaluation Criteria In Solid Tumors v1.1, Response Assessment in Neuro-Oncology (RANO) (HGG) or modified RANO (LGG) criteria, and duration of response (DOR).^1,2

Pediatric Studies

CTMT212X2101 (X2101) Study

Study X2101 was a multicenter, open-label, multiple-cohort study in pediatric patients with refractory or recurrent solid tumors.

• Part C was a dose-escalation phase of TAFINLAR + MEKINIST in patients with BRAF V600E–mutant tumors

• Part D was a cohort-expansion phase of TAFINLAR + MEKINIST in patients with BRAF V600E–mutant LGG

The major efficacy outcome was ORR as assessed by an independent review committee per RANO criteria. The efficacy of TAFINLAR + MEKINIST was evaluated in 48 patients, including those with LGG (n=34) and HGG (n=2).^1,2

CDRB436G2201 (G2201) Study

TAFINLAR + MEKINIST was evaluated in a multicenter, randomized, open-label, phase 2 study in chemotherapy-naive pediatric patients with BRAF V600E–mutant LGG and patients with relapsed or progressive BRAF V600E–mutant HGG.

Patients with HGG (N=41) were enrolled in a single-arm cohort. The major efficacy outcome measure for the HGG cohort was ORR as assessed by independent review committee per RANO 2010 criteria.^1,2

Response Rates (Adult and Pediatric Patients)

TAFINLAR + MEKINIST demonstrated efficacy in a range of solid tumors

Broad antitumor activity across multiple studies: Up to 80%* ORR in adults with various BRAF V600E–mutant solid tumors^1,2

Proven response across various BRAF V600E–mutant solid tumors in adults and children^1,2,a

ATC, anaplastic thyroid cancer; ORR, overall response rate; PR, partial response.
*In tumor types with N>4.
^aExcludes non-small cell lung cancer (N=6) (previously approved tumor type for TAFINLAR + MEKINIST). Data for ATC were assessed in patients with locally advanced, unresectable, or metastatic disease, and no standard locoregional treatment options.^1,2
bPatients with pediatric low-grade glioma evaluated in this dataset represent a previously treated population with refractory or recurrent tumors. Therefore, data differ from results seen in the separately approved pediatric low-grade glioma indication, which included patients who required their first systemic treatment (ORR: 46.6%; N=73).^1,2

No response achieved in the following tumor types^1,2:

• Adenocarcinoma pancreas (N=3)

• Mixed ductal/adenoneuroendocrine carcinoma (N=2)

• Neuroendocrine carcinoma of colon (N=2)

• Adenocarcinoma of anus (N=1)

• Gastrointestinal stromal tumors (N=1)

Duration of Response Across Multiple Tumor Types

DOR in the ROAR (adult) and NCI-MATCH (adult) Studies^1,2

DOR was not applicable for tumor types that had no response.

ATC, anaplastic thyroid cancer; BTC, biliary tract cancer; DOR, duration of response; HGG, high-grade glioma; LGG, low-grade glioma; LGSOC, low-grade serous ovarian carcinoma; NE, not estimable.
No additional DOR measures evaluated where marked “–“.
^aExcludes non-small cell lung cancer (N=6) (previously approved tumor type for TAFINLAR + MEKINIST). Data for ATC were assessed in patients with locally advanced, unresectable, or metastatic disease and no standard locoregional treatment options.^1,2
bDenotes a right-censored DOR.

DOR assessment in pediatric studies^1,2

• X2101 (HGG and LGG): For the 9 patients who responded, DOR was ≥6 months for 78% of patients and ≥24 months for 44% of patients

• G2201 (HGG cohort): Median DOR was not estimable (NE) (95% CI, 9.2-NE). For the 23 patients who responded, DOR was ≥6 months for 78% of patients, ≥12 months for 48% of patients, and ≥24 months for 22% of patients

ADDITIONAL INDICATION

TAFINLAR, in combination with MEKINIST, is indicated for the treatment of patients with locally advanced or metastatic anaplastic thyroid cancer (ATC) with BRAF V600E mutation and with no satisfactory locoregional treatment options.

NEXT: Safety Profile

References: 1. Tafinlar. Prescribing information. Novartis Pharmaceuticals Corp. 2. Mekinist. Prescribing information. Novartis Pharmaceuticals Corp.