In an interview with PharmaShots, Chris Arendt, Head of the Oncology Therapeutic Area Unit at Takeda shared his views on the new data of Alunbrig in the P-III ALTA-1L study for the Treatment of ALK+ mNSCLC

Shots:

• The P-III ALTA-1L study evaluates Alunbrig vs Crizotinib in patients with ALK+ mNSCLC who have not received prior treatment with an ALK inhibitor
• The results showed a 50% reduction in risk of disease progression or death with an m-PFS (24mos. vs 11mos.), 70% reduction in risk of disease progression in the brain, radiotherapy to the brain, or death with a PFS (24mos. vs 5.5mos.) In patients with baseline brain metastases; DoR (33mos. vs 14mos.) with a long-term follow up; m-iDoR (28mos. vs 9mos.); 3yrs. OS (74% vs 55%); confirmed intracranial ORR (78% vs 26%)
• The therapy showed clinical and statistical benefits including durable overall and intracranial efficacy while the safety profile has remained consistent and manageable

Tuba: Let’s discuss ALUNBRIG (brigatinib). What is ALUNBRIG’s mechanism of action, route of administration, formulation, frequency, etc.?

Chris Arendt: ALUNBRIG is a potent and selective next-generation tyrosine kinase inhibitor (TKI) that was designed to target oncogenic driver mutations in anaplastic lymphoma kinase (ALK). The recommended dosage and administration for ALUNBRIG is 90 mg orally once daily for the first seven days, which is then increased to 180 mg orally once daily.

In the U.S., ALUNBRIG is approved for the treatment of adult patients with anaplastic lymphoma kinase-positive (ALK+) locally advanced or metastatic non-small cell lung cancer (mNSCLC) as detected by a Food and Drug Administration (FDA)-approved test.

ALK+ NSCLC is a unique type of NSCLC caused by a mutation in the ALK gene. The median age of a person diagnosed with ALK+ NSCLC is 52 – more than 10 years younger than the total lung cancer population – and it is more often found in former or non-smokers. ALK+ NSCLC also has a clear predilection to spread to the brain. Up to 75% of patients with ALK+ NSCLC will ultimately develop brain metastases at some point during their disease. These characteristics emphasize the need for treatment methods that are not only effective both overall and intracranially, but also offer convenience and quality of life (QoL) for patients.

Tuba: Can you share an overview of the data presented at the European Society for Medical Oncology (ESMO) conference?

Chris Arendt: At this year’s ESMO, Takeda presented final results from the Phase 3 ALTA first-line (1L) trial investigating ALUNBRIG versus crizotinib in the treatment of patients with ALK+ mNSCLC who have not received prior treatment with an ALK inhibitor. ALUNBRIG demonstrated clinically and statistically meaningful benefits, including durable overall and intracranial efficacy.

Tuba: Please share the clinical results from the Phase 3 ALTA 1L study. Why are the results significant for patients?

Chris Arendt: Overall, ALUNBRIG reduced the risk of disease progression or death by greater than 50% compared with crizotinib, with a median progression-free survival (PFS) of 24 months as assessed by a blinded independent review committee (BIRC), versus 11 months for crizotinib.

• In patients with baseline brain metastases, ALUNBRIG reduced the risk of disease progression in the brain, radiotherapy to the brain, or death by greater than 70% compared with crizotinib, with a PFS of 24 months versus 5.5 months with crizotinib as assessed by a BIRC. With long-term follow-up, ALUNBRIG demonstrated duration of response (DoR) of 33 months versus 14 months for crizotinib as assessed by a BIRC.
• Median intracranial DoR (iDoR) in patients treated with ALUNBRIG was 28 months versus 9 months with crizotinib as assessed by a BIRC.
• Three-year overall survival (OS) was 74% for ALUNBRIG versus 55% for crizotinib in patients with baseline brain metastases as assessed by a BIRC.

These longer-term data from ALUNBRIG demonstrated durable overall and intracranial efficacy and a safety profile that remained consistent and manageable despite extended treatment duration. These results add to and remain consistent with previously reported data from the ALTA 1L trial and reinforce ALUNBRIG as an effective first-line treatment option in patients with ALK+ mNSCLC.

Tuba: Why are the results of the ALTA 1L trial significant? What does the availability of ALUNBRIG mean for patients with ALK+ NSCLC?

Chris Arendt: ALK+ NSCLC has a clear predilection to spread to the brain. Up to approximately 35% of ALK+ mNSCLC patients may already have brain metastases at diagnosis. After primary diagnosis, patients can develop metastases early, often within ~2 years, and up to 75% will ultimately develop brain metastases at some point during their disease. This can be debilitating to a patient’s QoL.

The most recent results from the ALTA 1L trial showed ALUNBRIG demonstrated a confirmed intracranial objective response rate (ORR) of 78% for patients with measurable brain metastases at baseline versus 26% for patients treated with crizotinib as assessed by BIRC, meaning that 78% of patients with measurable brain metastases at baseline treated with ALUNBRIG demonstrated a response to the treatment.

While there are several targeted treatment options available to treat ALK+ NSCLC, therapies that have demonstrated robust intracranial efficacy have shown to be an invaluable addition to the treatment landscape, as we seek to extend and improve the lives of patients.

Tuba: What are Takeda’s upcoming plans for ALUNBRIG? Is Takeda looking at ALUNBRIG in other indications?

Chris Arendt: We remain confident in ALUNBRIG’s role as a treatment for adults with ALK+ mNSCLC. We are focusing our efforts on the 1L setting, where we believe ALUNBRIG offers the most benefit for patients. ALUNBRIG has been approved in this setting by regulatory authorities around the world, including the U.S., EU, and Japan.

Tuba: Can you describe the ALK+ NSCLC market and ALUNBRIG’s current positioning?

Chris Arendt: Despite recent advancements, there is still a need for therapies with improved intracranial efficacy together with overall efficacy that can demonstrate better QoL outcomes. ALUNBRIG has shown compelling benefits, including intracranial efficacy, in the ALTA 1L trial and also offers dosing convenience as oral medicine. These proven benefits led the National Comprehensive Cancer Network (NCCN) to recommend ALUNBRIG as a preferred 1L treatment option for ALK+ mNSCLC, and we are pleased that it is available as a preferred 1L treatment option for newly diagnosed ALK+ mNSCLC patients around the world.

Tuba: What makes ALUNBRIG different compared to existing competitors in the ALK+ NSCLC treatment space?

Chris Arendt: While we do not comment on the products of other companies, we remain confident in ALUNBRIG’s role as a treatment for adults with ALK+ mNSCLC patients.

ALUNBRIG’s benefits, including overall and intracranial efficacy, tolerability, dosing convenience, and QoL are especially important for patients with newly diagnosed ALK+ NSCLC, who are often younger and in the middle of their lives but maybe on therapy for extended periods.

Tuba: What partnerships has Takeda formed to ensure ALUNBRIG can reach eligible patients?

Chris Arendt: Takeda is committed to identifying and collaborating with stakeholders across the oncology ecosystem to ensure our treatments can reach the hands of eligible patients. 

To that end, we have entered into an agreement with Point32Health, one of the first risk-sharing contracts in oncology. The agreement will make ALUNBRIG broadly available to Point32Health’s more than two million members while minimizing financial risk for Point32Health through an outcomes-based structure. Through this collaboration, Point32Health can allow broader access to ALUNBRIG because Takeda stands behind the value of its medicine and is willing to minimize the financial risk.

Additionally, Takeda’s partnerships with diagnostic companies, ThermoFisher and Foundation Medicine, support the development of blood and tissue-based diagnostics, allowing us to help physicians make informed treatment decisions through the use of robust, accurate, and timely diagnostic testing so that advanced cancer patients receive the optimal therapy for their disease.

Source: UT Southwestern Medical Center

About Author: Chris Arendt is the Head of the Oncology Therapeutic Area Unit at Takeda. Dr. Arendt received his Ph.D. in immunology from the University of Alberta. He completed his postdoctoral training at the Skirball Institute of Biomolecular Medicine at NYU Medical Center, supported by the Medical Research Council of Canada and Howard Hughes Medical Institute. Dr. Arendt spent more than 13 years at Sanofi