Alectinib + Chemotherapy for Non-Small Cell Lung Cancer

(HORIZON 2 Trial)

Recruiting at 31 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

150 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination Alectinib, Carboplatin, Cisplatin, and Pemetrexed for treating non-small cell lung cancer?

Research shows that combining pemetrexed with cisplatin or carboplatin is effective for treating advanced non-small cell lung cancer (NSCLC). This suggests that using these drugs together could help in managing NSCLC. ^{1 2 3 4 5}

Is the combination of Alectinib and chemotherapy safe for humans?

Alectinib is generally well tolerated but can cause serious side effects like skin reactions and liver issues. Most side effects can be managed by adjusting the dose, and its safety profile remains consistent over time. ^{6 7 8 9 10}

How does the drug Alectinib combined with chemotherapy differ from other treatments for non-small cell lung cancer?

Alectinib combined with chemotherapy is unique because it targets ALK-positive non-small cell lung cancer, which is a specific genetic mutation, whereas many other treatments focus on different mutations or use immunotherapy. This combination may offer a new option for patients who have progressed on other targeted therapies. ^{2 11 12 13 14}

What is the purpose of this trial?

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 II cohort that will evaluate the safety, and efficacy of alectinib in combination with up to four cycles of platinum-based chemotherapy in the adjuvant setting post complete surgical resection. Cohort B2 is a phase II cohort that will evaluate the efficacy and safety of perioperative alectinib in combination with chemotherapy in the neoadjuvant setting.

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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 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 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]

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]

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]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Clinical effectiveness of pemetrexed combined with cisplatin chemotherapy for advanced and maintenance treatment for patients with non-small-cell lung cancer. [2019]

2. United States 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. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Second-line epidermal growth factor receptor inhibitors followed by third-line pemetrexed or the reverse sequence: a retrospective analysis of 83 Chinese patients with advanced lung adenocarcinoma. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Randomised, double-blind trial of carboplatin and paclitaxel with daily oral cediranib or placebo in patients with advanced non-small cell lung cancer: NCIC Clinical Trials Group study BR29. [2015]

5. England pubmed.ncbi.nlm.nih.gov

Pemetrexed plus cisplatin/carboplatin in previously treated locally advanced or metastatic non-small cell lung cancer patients. [2021]

6. England 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. [2023]

7. England 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. [2022]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Successful Treatment with Ensartinib After Alectinib-induced Hyperbilirubinemia in ALK-Positive NSCLC. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Successful alectinib desensitization in a patient with anaplastic lymphoma kinase-positive adenocarcinoma of the lung and alectinib-induced drug rash. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Alectinib-Induced Erythema Multiforme and Successful Rechallenge with Alectinib in a Patient with Anaplastic Lymphoma Kinase-Rearranged Lung Cancer. [2020]

11. England 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. [2023]

12. China 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). [2023]

13. United States pubmed.ncbi.nlm.nih.gov

Pemetrexed in advanced NSCLC: a review of the clinical data. [2015]

14. Netherlands 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. [2019]