Takeda Pharmaceutical Company Limited today announced that the U.S. Food and Drug Administration (FDA) approved ALUNBRIG (brigatinib) for adult patients with anaplastic lymphoma kinase-positive (ALK+) metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test. This approval expands ALUNBRIG’s current indication to include the first-line setting. ALUNBRIG is a potent and selective next-generation tyrosine kinase inhibitor (TKI) designed to target ALK molecular alterations.

“We’re extremely proud of the positive results ALUNBRIG has shown for newly diagnosed ALK+ NSCLC patients, particularly those with brain metastases,” said Teresa Bitetti, President, Global Oncology Business Unit, Takeda. “Through a robust clinical development program and ongoing investigations across the NSCLC treatment landscape, Takeda is committed to uncovering solutions for people living with devastating forms of lung cancer in need of new options. We believe this approval for ALUNBRIG is a substantial step in the right direction and represents significant progress for Takeda’s broader lung cancer portfolio.”

The approval is based on results from the Phase 3 ALTA 1L trial, which is evaluating the safety and efficacy of ALUNBRIG compared to crizotinib in adult patients with ALK+ locally advanced or metastatic NSCLC who have not received prior treatment with an ALK inhibitor.

“Results from the ALTA 1L trial add brigatinib to the very short list of first-line treatment options for ALK+ lung cancer patients that have proven to be superior to crizotinib. Compared to crizotinib, brigatinib demonstrated superior efficacy, especially among those with brain metastases at baseline, and a low pill burden, at one pill a day, which is an important factor when we could be controlling disease for years,” said Ross Camidge, MD, PhD, Joyce Zeff Chair in Lung Cancer Research, University of Colorado Cancer Center. “These data have established brigatinib’s potential in the first-line setting, and I’m confident the FDA approval will open a new window of possibilities for physicians and their patients.”

After more than two years of follow-up, results from the ALTA 1L trial showed ALUNBRIG demonstrated superiority over crizotinib, with significant anti-tumor activity observed, especially in patients with baseline brain metastases.

ALUNBRIG reduced the risk of disease progression or death twofold compared with crizotinib (PFS hazard ratio = 0.49), with a 24-month median progression-free survival (PFS) as assessed by a blinded independent review committee (BIRC) versus 11 months for crizotinib.

ALUNBRIG demonstrated a confirmed overall response rate (ORR) of 74% (95% CI: 66–81) for ALUNBRIG and 62% (95% CI: 53–70) for crizotinib as assessed by a BIRC.

ALUNBRIG demonstrated a confirmed intracranial ORR for patients with measurable brain metastases at baseline of 78% (95% CI: 52–94) for patients treated with ALUNBRIG and 26% (95% CI: 10–48) for patients treated with crizotinib.

“As with many forms of lung cancer, ALK+ NSCLC is a complex and aggressive cancer that presents various treatment challenges for patients who are newly diagnosed, including those whose disease has spread to their brain,” said Andrea Stern Ferris, President and CEO, LUNGevity Foundation. “Having this option for newly diagnosed patients is exciting news for the ALK+ NSCLC community and adds to the remarkable progress we have witnessed in lung cancer treatment over the past decade.”

About the ALTA 1L Trial

The Phase 3 ALTA 1L (ALK in Lung Cancer Trial of BrigAtinib in 1st Line) trial of ALUNBRIG in adults is a global, ongoing, randomized, open-label, comparative, multicenter trial, which enrolled 275 patients (ALUNBRIG, n=137, crizotinib, n=138) with ALK+ locally advanced or metastatic NSCLC who have not received prior treatment with an ALK inhibitor. Patients received either ALUNBRIG, 180 mg orally once daily with seven-day lead-in at 90 mg once daily, or crizotinib, 250 mg orally twice daily.

The median age was 58 years in the ALUNBRIG arm and 60 years in the crizotinib arm. Twenty-nine percent of patients had brain metastases at baseline in the ALUNBRIG arm versus 30% in the crizotinib arm. Twenty-six percent of patients received prior chemotherapy for advanced or metastatic disease in the ALUNBRIG arm versus 27% in the crizotinib arm.

Blinded independent review committee (BIRC)-assessed progression-free survival (PFS) was the major efficacy outcome measure. Additional efficacy outcome measures included confirmed overall response rate (ORR) per RECIST v1.1 and intracranial ORR.

The warnings and precautions for ALUNBRIG are: interstitial lung disease (ILD)/pneumonitis, hypertension, bradycardia, visual disturbance, creatine phosphokinase (CPK) elevation, pancreatic enzyme elevation, hyperglycemia and embryo-fetal toxicity.

In the ALTA 1L trial, serious adverse reactions occurred in 33% of patients receiving ALUNBRIG. The most common serious adverse reactions other than disease progression were pneumonia (4.4%), ILD/pneumonitis (3.7%), pyrexia (2.9%), dyspnea (2.2%), pulmonary embolism (2.2%), and asthenia (2.2%). Fatal adverse reactions other than disease progression occurred in 2.9% of patients and included pneumonia (1.5%), cerebrovascular accident (0.7%), and multiple organ dysfunction syndrome (0.7%).

The most common adverse reactions in the ALTA 1L trial (≥10%) with ALUNBRIG were diarrhea (53%), rash (40%), cough (35%), hypertension (32%), fatigue (32%), nausea (30%), myalgia (28%), dyspnea (25%), abdominal pain (24%), and headache (22%).