Amivantamab + Docetaxel for Non-Small Cell Lung Cancer

(swalloWTail Trial)

Recruiting at 14 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Janssen Research & Development, LLC

Must not be taking: Corticosteroids, Paclitaxel

Disqualifiers: Oncogenic mutations, ILD, others

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

Compensation: Varies

Number of Visits: 42

12 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the drug combination Amivantamab and Docetaxel for treating non-small cell lung cancer?

Research shows that docetaxel, when combined with other drugs like ramucirumab, can improve survival and response rates in non-small cell lung cancer patients who have progressed after initial treatments. This suggests that docetaxel may be effective in combination therapies for this type of cancer. ^{1 2 3 4 5}

Is the combination of Amivantamab and Docetaxel safe for humans?

The safety of docetaxel, one of the drugs in the combination, has been studied in patients with non-small cell lung cancer (NSCLC). These studies show that docetaxel can be used safely, but it may cause side effects like low blood cell counts and fatigue. However, there is no specific safety data available for the combination of Amivantamab and Docetaxel. ^{6 7 8 9 10}

How is the drug combination of Amivantamab and Docetaxel unique for treating non-small cell lung cancer?

The combination of Amivantamab and Docetaxel is unique because Amivantamab is a novel antibody that targets specific proteins involved in cancer growth, while Docetaxel is a well-established chemotherapy drug that disrupts cell division. This combination may offer a new approach by potentially enhancing the effectiveness of treatment through different mechanisms of action. ^{11 12 13 14 15}

What is the purpose of this trial?

The purpose of this study is to identify the recommended Phase 2 (combination) dose (RP2CD) of the amivantamab and docetaxel combination therapy in participants with metastatic non-small cell lung cancer (NSCLC) in Phase 1 (combination dose selection); and to evaluate the antitumor effect of the combination at the selected RP2CD in participants with NSCLC without oncogenic driver mutations with disease progression on platinum-based chemotherapy and immune checkpoint inhibitor, in the Phase 2 (expansion).

Research Team

Janssen Research &Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for people with metastatic non-small cell lung cancer who have seen their disease progress after platinum-based chemotherapy and immune checkpoint inhibitor treatment. Participants should not have oncogenic driver mutations.

Inclusion Criteria

I have at least one tumor that can be measured and hasn't been treated with radiation.

I had another type of cancer, but it won't affect this study's treatment.

I am fully active or can carry out light work.

Exclusion Criteria

I have or had cancer spread to the lining of the brain and spine or untreated spinal cord compression.

My cancer has specific genetic changes (like EGFR, MET).

Medical history of (non-infectious) ILD/pneumonitis, or has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening- Participant has history of any significant drug allergy (such as anaphylaxis, hepatotoxicity, or immune-mediated thrombocytopenia or anemia) or has known allergies, hypersensitivity, or intolerance to: a. amivantamab or amivantamab excipients (refer to the amivantamab IB); b.docetaxel, docetaxel excipients or to other drugs formulated with polysorbate and paclitaxel

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1: Combination Dose Selection

Participants receive amivantamab and docetaxel to determine the recommended Phase 2 combination dose (RP2CD). Doses are adjusted based on dose limiting toxicities.

Up to 21 days

Multiple visits per 21-day cycle

Phase 2: Dose Expansion

Participants receive amivantamab and docetaxel at the RP2CD to evaluate antitumor effects. Treatment continues until disease progression or unacceptable toxicity.

Up to 1 year 4 months

Regular visits per 21-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Amivantamab
• Docetaxel

Trial Overview The study is testing a combination of two drugs, Amivantamab and Docetaxel, to determine the best dose for Phase 2 trials and to assess how well this combo works in treating NSCLC at that dose.

Participant Groups

Group I: Phase 2 (Dose Expansion) Experimental Treatment 2 Interventions

Participants will receive amivantamab in combination with docetaxel in 2 cohorts (Cohort A \[adenocarcinoma\] and Cohort B \[squamous\]) at the RP2CD determined in Phase 1. Participants will continue study treatment until disease progression, unacceptable toxicity, or until another criterion for discontinuation of study treatment is met.

Group II: Phase 1 (Combination Dose Selection) Experimental Treatment 2 Interventions

Participants will receive amivantamab intravenous (IV) infusion administered based on body weight from Cycle 1 Day 1, Day 2, and subsequent doses on Days 8 and 15, and then on Day 1 of each 21-day treatment cycle. Docetaxel will be administered on Day 2 of Cycle 1 (before Day 2 amivantamab infusion) and then on Day 1 of each 21-day treatment cycle, thereafter. Doses will be escalated or de-escalated based on the dose limiting toxicities (DLTs) and the recommended Phase 2 combination dose (RP2CD) will be determined. Participants will continue study treatment until disease progression, unacceptable toxicity, or until another criterion for discontinuation of study treatment is met.

Amivantamab is already approved in United States, European Union for the following indications:

Approved in United States as Rybrevant for:

• Locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations
• Locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations

Approved in European Union as Rybrevant for:

• Locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations
• Locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

In a phase 2 trial involving 40 chemotherapy-naïve patients with advanced nonsquamous NSCLC, the combination of carboplatin, docetaxel, and bevacizumab resulted in a median progression-free survival of 7.9 months and a median overall survival of 16.5 months, indicating its effectiveness as a front-line treatment.

The treatment was generally tolerable, with a high disease control rate of 95%, although some patients experienced significant adverse events, including infections and bleeding, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 study of carboplatin, docetaxel, and bevacizumab as frontline treatment for advanced nonsmall-cell lung cancer. William, WN., Kies, MS., Fossella, FV., et al.[2018]

In a study of 39 chemotherapy-naïve patients with advanced non-small cell lung cancer, the combination of irinotecan and docetaxel resulted in a partial response in 23% of patients, with a median survival time of 10.8 months and a 1-year survival rate of 42.2%.

The treatment was associated with manageable side effects, including grade 4 neutropenia in 10.3% of patients and grade 3 or 4 diarrhea in 23.1%, indicating that this non-platinum-based regimen could be a viable option for patients who cannot tolerate traditional platinum-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Front-line treatment of advanced non-small cell lung cancer with irinotecan and docetaxel: a multicentre phase II study. Ziotopoulos, P., Androulakis, N., Mylonaki, E., et al.[2018]

This phase 2 study aims to evaluate the safety and preliminary efficacy of a combination treatment of docetaxel, ramucirumab, and pembrolizumab in 41 patients with metastatic or recurrent non-small-cell lung cancer (NSCLC) who have progressed after standard therapies.

The primary goal is to assess the 6-month progression-free survival (PFS) rate, which could provide insights into new treatment strategies for NSCLC, especially for patients who have not responded to previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 2 Study of Docetaxel, Ramucirumab, and Pembrolizumab for Patients With Metastatic or Recurrent Non-Small-Cell Lung Cancer (NSCLC) who Progressed on Platinum-Doublet and PD-1/PD-L1 Blockade. Osta, BE., Carlisle, J., Steuer, C., et al.[2023]

In a study of 30 patients with previously treated non-squamous non-small cell lung cancer, the addition of bevacizumab to docetaxel or pemetrexed resulted in a median progression-free survival of 5.0 months and an overall survival of 15.8 months, indicating potential efficacy in this salvage treatment setting.

While the treatment was generally well tolerated, there was a notable 10% incidence of osteonecrosis of the jaw, highlighting the need for careful monitoring of this side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab with Single-agent Chemotherapy in Previously Treated Non-squamous Non-small-cell Lung Cancer: Phase II Study. Yamaguchi, K., Masuda, T., Fujitaka, K., et al.[2019]

In a subgroup analysis of 89 East Asian patients with stage IV non-small cell lung cancer, the combination of docetaxel and ramucirumab showed improved overall survival (15.44 months) and progression-free survival (4.88 months) compared to docetaxel plus placebo, aligning with results from the overall study of 1,253 patients.

Reducing the starting dose of docetaxel from 75 mg/m2 to 60 mg/m2 in East Asian patients led to improved safety outcomes, with a lower incidence of neutropenia and febrile neutropenia, highlighting the importance of dose adjustments in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

East Asian Subgroup Analysis of a Randomized, Double-Blind, Phase 3 Study of Docetaxel and Ramucirumab Versus Docetaxel and Placebo in the Treatment of Stage IV Non-small Cell Lung Cancer Following Disease Progression after One Prior Platinum-Based Therapy (REVEL). Park, K., Kim, JH., Cho, EK., et al.[2023]

In a phase I trial involving 27 patients with advanced refractory cancer, the combination of sorafenib and docetaxel showed significant alterations in the pharmacokinetics of docetaxel, with increases in both the area under the concentration-time curve (AUC) and maximum concentration (Cmax).

The treatment was associated with a high incidence of adverse events, particularly dermatologic issues, leading to dose adjustments; however, 11% of patients experienced partial responses and 52% had stable disease, suggesting some efficacy in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial to investigate the safety, pharmacokinetics and efficacy of sorafenib combined with docetaxel in patients with advanced refractory solid tumours. Awada, A., Hendlisz, A., Christensen, O., et al.[2018]

In a phase II study involving 160 Japanese patients with non-small cell lung cancer (NSCLC), the combination of ramucirumab and docetaxel significantly prolonged progression-free survival (PFS) compared to placebo-docetaxel, with a median PFS of 5.22 months versus 4.21 months.

While overall survival rates were similar between the two groups, the ramucirumab-docetaxel combination showed a higher objective response rate (28.9% vs 18.5%) and a higher disease control rate (78.9% vs 70.4%), although it was associated with a higher incidence of febrile neutropenia (34.2% vs 19.8%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, phase II study of ramucirumab plus docetaxel vs placebo plus docetaxel in Japanese patients with stage IV non-small cell lung cancer after disease progression on platinum-based therapy. Yoh, K., Hosomi, Y., Kasahara, K., et al.[2023]

In a study of 130 patients with recurrent non-small-cell lung cancer (NSCLC), combining docetaxel with irinotecan did not significantly improve overall survival or response rates compared to docetaxel alone, but it did prolong the time to tumor progression (5.6 months vs. 4.8 months).

While the combination treatment had similar rates of severe neutropenia and anemia as docetaxel alone, it was associated with higher rates of thrombocytopenia and diarrhea, indicating a need to consider potential side effects when choosing treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of docetaxel and docetaxel-irinotecan combination as second-line chemotherapy in advanced non-small-cell lung cancer: a randomized phase II trial. Pectasides, D., Pectasides, M., Farmakis, D., et al.[2020]

In a Phase II study involving 46 patients with non-small cell lung cancer (NSCLC), the combination of docetaxel and irinotecan showed some efficacy, with 11% of patients achieving a confirmed response, but it was associated with significant toxicity.

The most common severe side effects included neutropenia (67%), diarrhea (28%), and fatigue (20%), leading to the conclusion that while the treatment has some activity, it is not recommended over single-agent therapies due to the high risk of adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II NCCTG study of irinotecan and docetaxel in previously treated patients with non-small cell lung cancer. Molina, JR., Nikcevich, D., Hillman, S., et al.[2018]

In a study of 27 patients with inoperable non-small-cell lung cancer (NSCLC) who had previously received platinum-based chemotherapy, docetaxel showed a partial response rate of 24%, indicating its effectiveness as a treatment option.

The main side effect observed was severe neutropenia in 75% of patients, highlighting the need for careful monitoring of blood cell counts during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of docetaxel in non-small cell lung cancer patients previously treated with platinum-containing chemotherapy. French Group of Pneumo-Cancerology]. Robinet, G., Thomas, P., Pérol, M., et al.[2018]

Docetaxel is an effective treatment for non-small cell lung cancer (NSCLC), showing comparable efficacy to newer platinum-based therapies in advanced stages, and has been approved for use in this context.

Clinical trials are ongoing to explore the best ways to combine docetaxel with other treatments, such as thoracic radiotherapy and molecularly targeted agents, to enhance its effectiveness in various stages of NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel in non-small cell lung cancer: a review. Davies, AM., Lara, PN., Mack, PC., et al.[2019]

Docetaxel, when combined with other agents like cisplatin and gemcitabine, shows promising response rates (up to 53%) and median survival times (8 to 13 months) in patients with non-small-cell lung cancer, based on multiple phase I and II trials.

The combinations of docetaxel with other treatments have manageable adverse effects, making them a viable option for patients, with ongoing phase III trials to further evaluate their effectiveness in first-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) in combination chemotherapy and in association with thoracic radiotherapy for the treatment of non-small-cell lung cancer. Thoracic Oncology Program. Ornstein, DL., Nervi, AM., Rigas, JR.[2022]

Docetaxel is an effective treatment for advanced non-small cell lung cancer (NSCLC), showing survival benefits in both first- and second-line therapy, and is comparable or superior to other platinum-based chemotherapy options.

The drug has a manageable toxicity profile and has shown promising results when combined with novel targeted agents in Phase II studies, indicating its versatility in treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel in advanced non-small cell lung cancer. Wakelee, H., Ramalingam, S., Belani, CP.[2018]

Docetaxel has been established as the preferred treatment for advanced non-small cell lung cancer that does not respond to initial chemotherapy, based on the results of two recent trials.

Ongoing trials are exploring the use of docetaxel not only as a primary treatment but also in combination with radiation therapy, indicating its potential versatility in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) in the treatment of non-small cell lung cancer: an international update. Kris, MG., Manegold, C.[2019]

Docetaxel has been established as the preferred treatment for advanced non-small cell lung cancer that does not respond to initial chemotherapy, based on the results of two recent trials.

Ongoing trials are exploring the use of docetaxel not only as a primary treatment but also in combination with radiation therapy, indicating its potential versatility in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) in the treatment of non-small cell lung cancer: An international update. Kris, MG., Manegold, C.[2019]

References

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

Phase 2 study of carboplatin, docetaxel, and bevacizumab as frontline treatment for advanced nonsmall-cell lung cancer. [2018]

2. Ireland pubmed.ncbi.nlm.nih.gov

Front-line treatment of advanced non-small cell lung cancer with irinotecan and docetaxel: a multicentre phase II study. [2018]

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

A Phase 2 Study of Docetaxel, Ramucirumab, and Pembrolizumab for Patients With Metastatic or Recurrent Non-Small-Cell Lung Cancer (NSCLC) who Progressed on Platinum-Doublet and PD-1/PD-L1 Blockade. [2023]

4. Greece pubmed.ncbi.nlm.nih.gov

Bevacizumab with Single-agent Chemotherapy in Previously Treated Non-squamous Non-small-cell Lung Cancer: Phase II Study. [2019]

5. Korea (South) pubmed.ncbi.nlm.nih.gov

East Asian Subgroup Analysis of a Randomized, Double-Blind, Phase 3 Study of Docetaxel and Ramucirumab Versus Docetaxel and Placebo in the Treatment of Stage IV Non-small Cell Lung Cancer Following Disease Progression after One Prior Platinum-Based Therapy (REVEL). [2023]

6. England pubmed.ncbi.nlm.nih.gov

Phase I trial to investigate the safety, pharmacokinetics and efficacy of sorafenib combined with docetaxel in patients with advanced refractory solid tumours. [2018]

7. Ireland pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, phase II study of ramucirumab plus docetaxel vs placebo plus docetaxel in Japanese patients with stage IV non-small cell lung cancer after disease progression on platinum-based therapy. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Comparison of docetaxel and docetaxel-irinotecan combination as second-line chemotherapy in advanced non-small-cell lung cancer: a randomized phase II trial. [2020]

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

A Phase II NCCTG study of irinotecan and docetaxel in previously treated patients with non-small cell lung cancer. [2018]

10. France pubmed.ncbi.nlm.nih.gov

[Efficacy of docetaxel in non-small cell lung cancer patients previously treated with platinum-containing chemotherapy. French Group of Pneumo-Cancerology]. [2018]

11. England pubmed.ncbi.nlm.nih.gov

Docetaxel in non-small cell lung cancer: a review. [2019]

12. England pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) in combination chemotherapy and in association with thoracic radiotherapy for the treatment of non-small-cell lung cancer. Thoracic Oncology Program. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Docetaxel in advanced non-small cell lung cancer. [2018]

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

Docetaxel (Taxotere) in the treatment of non-small cell lung cancer: an international update. [2019]

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

Docetaxel (Taxotere) in the treatment of non-small cell lung cancer: An international update. [2019]