CLINICAL TRIALS PROFILE FOR ALECENSA

All Clinical Trials for Alecensa

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT02013219 ↗	A Phase 1b Study of Atezolizumab in Combination With Erlotinib or Alectinib in Participants With Non-Small Cell Lung Cancer (NSCLC)	Completed	Hoffmann-La Roche	Phase 1	2014-04-03	This open-label, multicenter study will assess the safety, tolerability, and pharmacokinetics of intravenous (IV) dosing of atezolizumab in combination with oral erlotinib or alectinib in participants with NSCLC. This study has two stages. In the erlotinib group, the combination treatment will be given to participants with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-treatment-naive, advanced (nonresectable) NSCLC in a safety-evaluation stage and to participants with previously untreated EGFR mutation-positive, advanced NSCLC in an expansion stage (Stage 2). In the alectinib group, for both the safety-evaluation and expansion stages (Stages 1 and 2), the combination will be given to participants who are treatment-naive with anaplastic lymphoma kinase (ALK)-positive advanced NSCLC. In Stage 1, erlotinib will be given at a starting dose of 150 milligrams (mg) by mouth (PO) once daily (QD) and the starting dose of alectinib will be 600 mg twice daily (BID), for 28 consecutive days during Cycle 1 and on Days 1 through 21 of each cycle thereafter. The starting dose of atezolizumab will be 1200 mg, administered every 3 weeks (q3W) starting on Day 8 of Cycle 1. If the starting regimen for a combination treatment is not tolerated, alternative doses and/or schedules of erlotinib and atezolizumab or alectinib and atezolizumab may be tested to determine potential recommended Phase 2 dose (RP2D) for that combination treatment. In Stage 2, a potential RP2D and schedule for each combination treatment will be investigated in an expansion cohort. For both stages, continuation of treatment beyond Cycle 1 will be at the discretion of the treating investigator. Study treatment will be discontinued in participants who experience disease progression or unacceptable toxicity, are not compliant with the study protocol, or, in their opinion or in the opinion of the investigator, are not benefiting from study treatment. However, in the absence of unacceptable toxicity, participants with second-line or greater NSCLC who are still receiving atezolizumab at the time of radiographic disease progression may be permitted to continue study treatment.
NCT02091141 ↗	My Pathway: A Study Evaluating Herceptin/Perjeta, Tarceva, Zelboraf/Cotellic, Erivedge, Alecensa, and Tecentriq Treatment Targeted Against Certain Molecular Alterations in Participants With Advanced Solid Tumors	Active, not recruiting	Genentech, Inc.	Phase 2	2014-04-14	This multicenter, non-randomized, open-label study will evaluate the efficacy and safety of six treatment regimens in participants with advanced solid tumors for whom therapies that will convey clinical benefit are not available and/or are not suitable options per the treating physician's judgment.
NCT02314481 ↗	Deciphering Antitumour Response and Resistance With INtratumour Heterogeneity	Recruiting	Hoffmann-La Roche	Phase 2	2017-05-12	DARWIN II is a multi-arm non-randomised phase II trial, Eligible patient will be those who relapse with NSCLC (clinical trials.gov ref. NCT02183883). Patients must have at least two tissue/DNA samples of their disease available for sequencing. The trial will investigate assess if intra-tumour heterogeneity (clonal vs subclonal actionable mutation) is associated with PFS. Patients without an actionable mutation will receive MPDL3280A (atezolizumab), a monoclonal antibody targeting anti-PDL1, as monotherapy or in combination with chemotherapy, The options for combination therapy will vary depending on the histology of the NSCLC (i.e. non-squamous or squamous). Patients with BRAFV600 mutations, HER2 Amplification, ALK/RET gene rearrangements will be enrolled into arms treating with vemurafenib, trastuzumab emtansine and alectinib respectively. DARWIN II will include extensive exploratory biomarker analysis to investigate a number of genomic and immune markers that may predict response to MPDL3280A (atezolizumab) and help guide future clinical trial design.
NCT02314481 ↗	Deciphering Antitumour Response and Resistance With INtratumour Heterogeneity	Recruiting	University College, London	Phase 2	2017-05-12	DARWIN II is a multi-arm non-randomised phase II trial, Eligible patient will be those who relapse with NSCLC (clinical trials.gov ref. NCT02183883). Patients must have at least two tissue/DNA samples of their disease available for sequencing. The trial will investigate assess if intra-tumour heterogeneity (clonal vs subclonal actionable mutation) is associated with PFS. Patients without an actionable mutation will receive MPDL3280A (atezolizumab), a monoclonal antibody targeting anti-PDL1, as monotherapy or in combination with chemotherapy, The options for combination therapy will vary depending on the histology of the NSCLC (i.e. non-squamous or squamous). Patients with BRAFV600 mutations, HER2 Amplification, ALK/RET gene rearrangements will be enrolled into arms treating with vemurafenib, trastuzumab emtansine and alectinib respectively. DARWIN II will include extensive exploratory biomarker analysis to investigate a number of genomic and immune markers that may predict response to MPDL3280A (atezolizumab) and help guide future clinical trial design.

Clinical Trial Conditions for Alecensa

Condition Name

Condition Name for Alecensa
Intervention	Trials
Non-small Cell Lung Cancer	7
Neoplasms	3
Solid Tumors	3
Haematological Malignancy	2

Condition MeSH

Condition MeSH for Alecensa
Intervention	Trials
Lung Neoplasms	11
Carcinoma, Non-Small-Cell Lung	11
Neoplasms	6
Ovarian Neoplasms	2

Clinical Trial Locations for Alecensa

Trials by Country

Trials by Country for Alecensa
Location	Trials
United States	135
China	9
France	9
Italy	8
Spain	8

Trials by US State

Trials by US State for Alecensa
Location	Trials
California	8
New York	7
Texas	6
Massachusetts	6
Maryland	5

Clinical Trial Progress for Alecensa

Clinical Trial Phase

Clinical Trial Phase for Alecensa
Clinical Trial Phase	Trials
Phase 3	1
Phase 2/Phase 3	3
Phase 2	13

Clinical Trial Status

Clinical Trial Status for Alecensa
Clinical Trial Phase	Trials
Recruiting	13
Not yet recruiting	3
Active, not recruiting	3

Clinical Trial Sponsors for Alecensa

Sponsor Name

Sponsor Name for Alecensa
Sponsor	Trials
Hoffmann-La Roche	7
Genentech, Inc.	5
Roche Pharma AG	2

Sponsor Type

Sponsor Type for Alecensa
Sponsor	Trials
Other	32
Industry	24
NIH	1

ALECENSA: A Groundbreaking Treatment for ALK-Positive Non-Small Cell Lung Cancer

Introduction to ALECENSA

ALECENSA (alectinib) is an oral anaplastic lymphoma kinase (ALK) inhibitor developed by Genentech, a member of the Roche Group. It has been a pivotal treatment in the management of ALK-positive non-small cell lung cancer (NSCLC), particularly in advanced and metastatic settings. Recent clinical trials and regulatory approvals have expanded its use to early-stage disease, marking a significant advancement in the treatment of this cancer type.

Clinical Trials Update: ALINA Study

The Phase III ALINA study has been a cornerstone in the recent clinical development of ALECENSA. This randomized, open-label, multicenter study compared ALECENSA with platinum-based chemotherapy in patients with completely resected Stage IB (tumor ≥ 4 cm) to IIIA (UICC/AJCC 7th edition) ALK-positive NSCLC[1][2][4].

Key Findings

• Disease-Free Survival (DFS): ALECENSA demonstrated a statistically significant and clinically meaningful improvement in DFS, reducing the risk of disease recurrence or death by an unprecedented 76% compared to platinum-based chemotherapy[2][4].
• Central Nervous System (CNS) DFS: A clinically meaningful improvement in CNS-DFS was also observed, with a hazard ratio of 0.22 (95% CI: 0.08-0.58)[4].
• Safety and Tolerability: The safety profile of ALECENSA in this trial was consistent with previous trials in the metastatic setting, with no unexpected safety findings. Grade 3 or 4 adverse events occurred in 30% of patients receiving ALECENSA, compared to 31% in the chemotherapy arm[4].

Impact on Treatment Paradigm

The results from the ALINA study are potentially practice-changing, as they suggest ALECENSA could become a new standard of care for early-stage ALK-positive lung cancer. According to Professor Benjamin Solomon, Medical Oncologist at Peter MacCallum Cancer Centre, Australia, "The magnitude of disease-free survival observed in this study could represent a paradigm shift in the way we manage early-stage ALK-positive lung cancer"[4].

Regulatory Approvals

FDA Approval

On April 18, 2024, the US Food and Drug Administration (FDA) approved ALECENSA for use as adjuvant therapy in completely resected ALK-positive NSCLC patients, based on the compelling results from the ALINA trial. This approval makes ALECENSA the first-ever adjuvant therapy for such patients[2].

Market Analysis and Projections

Global Market Reach

The approval of ALECENSA as an adjuvant therapy is expected to significantly broaden its global market reach. According to GlobalData, more than 33,000 ALK-positive stage I–III NSCLC patients are diagnosed annually in the eight major markets (China, France, Germany, Italy, Japan, Spain, the UK, and the US)[2].

Sales Projections

ALECENSA is projected to generate $2.2 billion in global sales by 2029, outpacing its nearest competitor, Pfizer’s Lorbrena (lorlatinib), which is expected to achieve $854 million in sales by the same year[2].

Epidemiology and Need for Effective Treatments

The anticipated number of ALK-positive NSCLC cases in the eight major markets is expected to reach 76,887 cases by 2029, highlighting the growing need for effective treatments in this area[2].

Ongoing and Future Clinical Trials

HORIZON-01 Clinical Trial

Roche is currently exploring ALECENSA’s potential as an adjuvant therapy following chemoradiation for unresectable, locally advanced, stage III NSCLC patients with an ALK gene fusion/rearrangement through the Phase III HORIZON-01 clinical trial (NCT05170204). If this trial meets expectations, it could further expand ALECENSA’s market reach[2].

Benefits of ALECENSA in Advanced Settings

Efficacy in Advanced NSCLC

In advanced settings, ALECENSA has shown significant efficacy. In clinical trials, 38% to 44% of patients experienced partial shrinkage of their cancer, with durations ranging from 7.5 to 11.2 months. Additionally, 61% of patients with measurable brain lesions had a complete or partial reduction of these lesions, lasting an average of 9.1 months[3].

Central Nervous System Metastases

ALECENSA is particularly beneficial for patients with central nervous system metastases, a common complication in ALK-positive lung cancer patients who are typically diagnosed at a younger age[2].

Overall Survival Data

Long-Term Survival

In the first-line setting, 60% of patients who started ALECENSA were still alive at 5 years, highlighting its long-term survival benefits[5].

Safety and Tolerability

Adverse Events

The safety profile of ALECENSA has been consistent across various trials. In the ALINA study, Grade 3 or 4 adverse events occurred in 30% of patients receiving ALECENSA, with no Grade 5 events observed. The discontinuation rate due to adverse events was 5.5% in the ALECENSA arm, compared to 12.5% in the chemotherapy arm[4].

Key Takeaways

• Clinical Efficacy: ALECENSA has demonstrated a statistically significant and clinically meaningful improvement in DFS in early-stage ALK-positive NSCLC.
• Regulatory Approval: FDA approval as an adjuvant therapy marks a significant milestone in the treatment of ALK-positive NSCLC.
• Market Projections: Projected to generate $2.2 billion in global sales by 2029, outpacing competitors.
• Ongoing Trials: Exploration of ALECENSA’s potential in unresectable, locally advanced NSCLC through the HORIZON-01 trial.
• Safety and Tolerability: Consistent safety profile with no unexpected findings.

FAQs

What is ALECENSA and how does it work?

ALECENSA (alectinib) is an oral anaplastic lymphoma kinase (ALK) inhibitor that targets and inhibits the ALK protein in cancer cells, preventing the growth and spread of ALK-positive NSCLC.

What are the key findings of the ALINA study?

The ALINA study showed that ALECENSA reduced the risk of disease recurrence or death by 76% compared to platinum-based chemotherapy in early-stage ALK-positive NSCLC patients.

Has ALECENSA been approved by regulatory authorities?

Yes, ALECENSA was approved by the FDA on April 18, 2024, for use as adjuvant therapy in completely resected ALK-positive NSCLC patients.

What are the projected sales of ALECENSA by 2029?

ALECENSA is projected to generate $2.2 billion in global sales by 2029, according to GlobalData.

What ongoing clinical trials are exploring the potential of ALECENSA?

The Phase III HORIZON-01 clinical trial is currently exploring ALECENSA’s potential as an adjuvant therapy following chemoradiation for unresectable, locally advanced, stage III NSCLC patients with an ALK gene fusion/rearrangement.

Sources

1. Genentech Press Release: "Genentech’s Alecensa Delivers Unprecedented Benefit in Early-Stage ALK-Positive Lung Cancer" - August 31, 2023.
2. Clinical Trials Arena: "FDA approves Alecensa as therapy for ALK-positive lung cancer" - May 2, 2024.
3. FDA Drug Trials Snapshots: "ALECENSA" - January 28, 2016.
4. Genentech Press Release: "Genentech’s Alecensa Reduces the Risk of Disease Recurrence or Death by an Unprecedented 76% in People with ALK-Positive Early-Stage Non-Small Cell Lung Cancer" - October 17, 2023.
5. ALECENSA HCP Website: "Overall Survival Data: Primary & Exploratory 5-Year Landmark Analysis".

Last updated: 2024-12-31