Alectinib + Chemotherapy for Non-Small Cell Lung Cancer

(HORIZON 2 Trial)

Not currently recruiting at 71 trial locations

Overseen By Reference Study ID Number: BO43249 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Disqualifiers: Squamous histology, Prior cancer therapy, Pregnancy, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with early-stage non-small cell lung cancer (NSCLC) following surgery. It evaluates the effectiveness of alectinib, a targeted therapy, combined with chemotherapy, in preventing cancer recurrence. Participants in Cohort B1 will receive the treatment after surgery, while those in Cohort B2 will receive it both before and after surgery. The trial seeks individuals who have undergone complete tumor removal, have adenocarcinoma, and possess a gene change known as ALK fusion. As a Phase 3 trial, this treatment represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking cancer therapy.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that alectinib, when combined with certain chemotherapy drugs, generally has a manageable safety profile. While some side effects might occur, they are usually not serious and can be effectively managed. In earlier studies, patients taking alectinib achieved better results compared to those who only received chemotherapy.

The treatment includes alectinib and chemotherapy drugs such as carboplatin, cisplatin, and pemetrexed. These chemotherapy drugs are commonly used, and their side effects are well known. Typical side effects might include fatigue, nausea, and changes in blood cell counts, but these are expected and manageable.

Overall, past research indicates that alectinib with this chemotherapy has been well-tolerated, suggesting it is relatively safe. Discuss any concerns with the medical team conducting the trial, as they can provide advice tailored to individual health needs. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Alectinib combined with chemotherapy for non-small cell lung cancer because it represents a promising shift from standard treatments. Alectinib specifically targets ALK mutations, which are present in some lung cancers, offering a more personalized approach compared to traditional chemotherapy alone. In Cohort B1, the combination of Alectinib with platinum-based chemotherapy and subsequent long-term Alectinib monotherapy could enhance the treatment's effectiveness over a longer period. For Cohort B2, introducing Alectinib before and after surgery may help reduce tumor size pre-surgery and prevent recurrence post-surgery, potentially improving patient outcomes.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

In this trial, participants will receive alectinib combined with platinum-based chemotherapy. Research has shown that alectinib, when paired with platinum-based chemotherapy, can effectively treat non-small cell lung cancer (NSCLC). Studies have found that alectinib works well for patients with ALK-positive NSCLC, where cancer cells have a specific gene change. In one arm of this trial, participants will receive alectinib and chemotherapy before surgery, followed by alectinib monotherapy after surgery. Another arm will involve alectinib and chemotherapy without surgery. The combination of platinum and pemetrexed chemotherapy has shown moderate success after other treatments have stopped working. Overall, using alectinib with chemotherapy appears promising for treating early-stage NSCLC that can be surgically removed, especially for those with ALK-positive tumors. ^{6 7 8 9 10}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

This trial is for people with early-stage NSCLC who can undergo surgery. They must have a specific type of lung cancer (non-squamous adenocarcinoma), be in good physical condition, and have an ALK gene change. Surgery to remove the cancer should be possible with the intent to cure.

Inclusion Criteria

My lung cancer was completely removed with surgery, and no cancer cells were found at the edges of the tissue removed.

My lung cancer is stage II to early stage IIIB and is not squamous cell type.

I am fully active or can carry out light work.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive alectinib and platinum-based chemotherapy for up to 3 cycles prior to surgery

9 weeks

Surgery

Participants undergo surgical resection of the tumor

Adjuvant Treatment

Participants receive alectinib in combination with platinum-based chemotherapy for up to 4 cycles post-surgery

12 weeks

Alectinib Monotherapy

Participants receive alectinib monotherapy for up to 5 years

5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Alectinib
• Carboplatin
• Cisplatin
• Pemetrexed

Trial Overview The study tests how well and safely alectinib works with platinum-based chemo (cisplatin or carboplatin) before or after surgery. One group gets this combo as adjuvant therapy post-surgery, while another gets it as neoadjuvant therapy pre-surgery.

How Is the Trial Designed?

Group I: Cohort B2 Experimental Treatment 4 Interventions

Participants will receive alectinib and platinum-based chemotherapy for up to 3 cycles (cycle length = 3 weeks) prior to surgery, and alectinib monotherapy after surgery for up to 5 years after surgery.

Group II: Cohort B1 Experimental Treatment 4 Interventions

Participants will receive alectinib in combination with platinum-based chemotherapy for up to 4 cycles (cycle length = 3 weeks), followed by alectinib monotherapy for up to 5 years.

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Published Research Related to This Trial

Alectinib has been shown to significantly improve progression-free survival and overall survival compared to crizotinib in patients with advanced ALK-positive non-small-cell lung cancer, as demonstrated in the phase III ALEX study and confirmed in subsequent studies in Japanese and Asian populations.

The safety profile of alectinib is manageable, with most adverse events being treatable through dose reduction, and no new safety concerns have emerged during long-term follow-up, reinforcing its recommendation as a preferred first-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience and management of adverse events in patients with advanced ALK-positive non-small-cell lung cancer receiving alectinib. Dziadziuszko, R., Peters, S., Ruf, T., et al.[2023]

Alectinib, while effective for treating advanced non-small-cell lung cancer (NSCLC) with ALK rearrangements, can lead to serious side effects such as grade 4 hyperbilirubinemia, as seen in a patient after five months of treatment.

After discontinuing alectinib and using an artificial liver support system to manage the hyperbilirubinemia, the patient was successfully treated with ensartinib, achieving stable disease without recurrence of hyperbilirubinemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Treatment with Ensartinib After Alectinib-induced Hyperbilirubinemia in ALK-Positive NSCLC. Peng, L., Xiao, K., Cui, J., et al.[2022]

In a real-life study of 121 patients with advanced non-squamous non-small cell lung cancer, the combination of pembrolizumab and chemotherapy resulted in a median progression-free survival of 9 months and overall survival of 20.6 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with manageable side effects; however, 17.5% of patients experienced grade 3-4 adverse events, and there were two treatment-related deaths, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). Renaud, E., Ricordel, C., Corre, R., et al.[2023]

In a phase III trial involving 657 patients with advanced EGFR-mutated non-small-cell lung cancer, both amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy significantly improved progression-free survival (PFS) compared to standard chemotherapy, with median PFS of 6.3 and 8.3 months versus 4.2 months, respectively.

The combination therapies also showed a higher objective response rate (64% and 63% for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy, respectively) compared to chemotherapy (36%), although the amivantamab-lazertinib-chemotherapy regimen had more hematologic adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. Passaro, A., Wang, J., Wang, Y., et al.[2023]

In a study involving 239 patients with advanced non-small-cell lung cancer (NSCLC), the addition of carboplatin to pemetrexed did not significantly improve progression-free survival or overall survival compared to pemetrexed alone.

However, in patients with squamous cell tumors, adding carboplatin to pemetrexed showed a notable improvement in overall survival, suggesting that this combination may be beneficial for this specific subgroup and warrants further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed versus pemetrexed and carboplatin as second-line chemotherapy in advanced non-small-cell lung cancer: results of the GOIRC 02-2006 randomized phase II study and pooled analysis with the NVALT7 trial. Ardizzoni, A., Tiseo, M., Boni, L., et al.[2022]

Pemetrexed (Alimta) is an effective treatment for mesothelioma and shows comparable survival rates to docetaxel in advanced non-small-cell lung cancer (NSCLC) while causing significantly fewer and less severe side effects.

In combination with platinum agents, pemetrexed has demonstrated significant activity and a favorable toxicity profile, making it a promising option for treating thoracic malignancies and warranting further research with other novel drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed in advanced NSCLC: a review of the clinical data. Zinner, RG., Fossella, FV., Herbst, RS.[2015]

In a phase III trial involving 107 patients with advanced ALK-positive non-small-cell lung cancer, alectinib demonstrated a significantly longer median progression-free survival (PFS) of 9.6 months compared to just 1.4 months for standard chemotherapy, indicating its superior efficacy.

Alectinib also showed a higher objective response rate in patients with central nervous system disease (54.2% vs. 0% for chemotherapy) and had a more favorable safety profile, with fewer grade ≥3 adverse events (27.1% for alectinib vs. 41.2% for chemotherapy).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alectinib versus chemotherapy in crizotinib-pretreated anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer: results from the phase III ALUR study. Novello, S., Mazières, J., Oh, IJ., et al.[2022]

Immunotherapy, particularly with pembrolizumab or atezolizumab combined with platinum-based chemotherapy, has become an effective first-line treatment for advanced non-small cell lung cancer (NSCLC), regardless of PD-L1 expression levels.

Patients with negative PD-L1 expression and low tumor mutational burden (TMB) may not benefit from immunotherapy combinations and might be better treated with traditional platinum-based chemotherapy, highlighting the need for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Choosing wisely first line immunotherapy in non-small cell lung cancer (NSCLC): what to add and what to leave out. Proto, C., Ferrara, R., Signorelli, D., et al.[2019]

In a study of 53 patients with advanced non-small cell lung cancer (NSCLC) who had previously undergone platinum-based chemotherapy, treatment with pemetrexed plus cisplatin or carboplatin resulted in a median overall survival of 10 months and a median progression-free survival of 6 months.

The treatment was generally well-tolerated, with only a small percentage of patients experiencing severe side effects, such as grade 3 or 4 leukopenia and thrombocytopenia, indicating that pemetrexed combined with platinum-based drugs can be a safe option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed plus cisplatin/carboplatin in previously treated locally advanced or metastatic non-small cell lung cancer patients. Zhang, GZ., Jiao, SC., Meng, ZT.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12167269/

Cost-Effectiveness of Adjuvant Alectinib Versus ... Our analysis suggests that adjuvant alectinib is dominant (ie, more effective and less costly) to platinum-based chemotherapy in Canadian patients with ...

2. clinicaltrials.gov clinicaltrials.gov/show/NCT06624059

NCT06624059 | A Study to See How Well and How Safely ... The objective of this study is to evaluate the efficacy and/or safety of multiple therapies in patients with early-stage resectable NSCLC. Cohort B1 is a phase ...

3. cda-amc.ca cda-amc.ca/sites/default/files/DRR/2025/PC0350-Alecensaro_Combined_Review.pdf

Alectinib (Alecensaro) Clinical features and outcome of patients with non–small-cell lung cancer who ... Alectinib in Resected ALK-Positive Non–Small-Cell Lung Cancer. N Engl J ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7058505/

Efficacy of platinum/pemetrexed combination chemotherapy in ... Platinum/pemetrexed-based chemotherapy shows modest efficacy in ALK-positive NSCLC after failure of second-generation ALK TKIs.

5. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03456076/

Clinical Trial: NCT03456076 A Study Comparing Adjuvant Alectinib Versus Adjuvant Platinum-Based Chemotherapy in Patients With ALK Positive Non-Small Cell Lung Cancer ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38598794/

Alectinib in Resected ALK-Positive Non-Small-Cell Lung ... Data on the efficacy and safety of ... alectinib significantly improved disease-free survival as compared with platinum-based chemotherapy.

7. nejm.org nejm.org/doi/abs/10.1056/NEJMoa2310532

Alectinib in Resected ALK-Positive Non–Small-Cell Lung ... Data on the efficacy and safety of adjuvant alectinib as compared with chemotherapy in patients with resected ALK-positive NSCLC are lacking.

8. sciencedirect.com sciencedirect.com/science/article/pii/S1556086424009444

16:45 OA13.04 ALINA Safety Results: Adjuvant Alectinib vs ... Alectinib had a manageable safety profile; coupled with the previously reported efficacy data, these results support the use of adjuvant alectinib in patients ...

9. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)04753-1/fulltext

LBA1 Efficacy and safety of adjuvant alectinib vs platinum- ... Adjuvant CT yields modest survival benefits in pts with resected early-stage ALK+ NSCLC. Alectinib has shown efficacy in pts with advanced ALK+ NSCLC. ALINA ( ...

10. chugai-pharm.co.jp chugai-pharm.co.jp/english/news/detail/20251021170000_1194.html

Alecensa Extends Median Overall Survival to Over 80 ... A Study Comparing Adjuvant Alectinib Versus Adjuvant Platinum Based Chemotherapy in Patients With ALK Positive Non-Small Cell Lung Cancer.