SAR408701 vs Docetaxel for Non-Small Cell Lung Cancer

(CARMEN-LC03 Trial)

Recruiting at 697 trial locations

Overseen By Trial Transparency email recommended (Toll free number for US & Canada)

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Sanofi

Must not be taking: Anticancer therapy, Antiretrovirals

Disqualifiers: Untreated brain metastases, AIDS, others

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

Compensation: Varies

Number of Visits: 2

Duration: 6.5 months for tusamitamab ravtansine, 4 months for docetaxel

389 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on any other anticancer therapy while participating in this study.

What data supports the effectiveness of the drug docetaxel for treating non-small cell lung cancer?

Docetaxel has been shown to be effective in treating advanced non-small cell lung cancer (NSCLC), both as a single agent and in combination with other drugs. Clinical trials have demonstrated that it improves survival and quality of life for patients, and it is approved for use in both first- and second-line therapy for advanced NSCLC. ^{1 2 3 4 5}

Is the treatment SAR408701 vs Docetaxel safe for humans?

Docetaxel, also known as Taxotere, has been widely used and studied for treating various cancers, including lung cancer. It is generally considered safe, but common side effects include neutropenia (low white blood cell count), peripheral edema (swelling), and less frequently, hypersensitivity reactions. These side effects are usually manageable with proper medical care. ^{1 6 7 8 9}

What makes the drug tusamitamab ravtansine unique for treating non-small cell lung cancer?

Tusamitamab ravtansine is unique because it combines a monoclonal antibody with a chemotherapy agent, targeting cancer cells more precisely than traditional chemotherapy like docetaxel, which is a standard treatment for advanced non-small cell lung cancer. ^{1 10 11 12 13}

What is the purpose of this trial?

Primary Objectives: * Study was designed with multiple primary endpoints analyzed on randomized participants at the time of the cut-off date for each given analysis (progression free survival \[PFS\] and overall survival \[OS\]) * Study success was defined either on PFS or OS * The primary objective was to determine whether tusamitamab ravtansine improves the progression free survival (PFS) when compared to docetaxel in participants with metastatic non-squamous non-small-cell lung cancer (NSCLC) expressing CEACAM5 greater than or equal to 2+ in intensity in at least 50% of the tumor cell population and previously treated with standard-of-care platinum-based chemotherapy and an immune checkpoint inhibitor (ICI) * The primary objective was to determine whether tusamitamab ravtansine improves the overall survival (OS) when compared with docetaxel in participants with metastatic non-squamous NSCLC expressing CEACAM5 greater than or equal to 2+ in intensity in at least 50% of the tumor cell population and previously treated with standard-of-care platinum-based chemotherapy and an immune checkpoint inhibitor. Secondary Objectives: * Compared the objective response rate (ORR) of tusamitamab ravtansine with docetaxel * Compared the health-related quality of life (HRQOL) of tusamitamab ravtansine with docetaxel * Evaluated the safety of tusamitamab ravtansine compared to docetaxel * Assessed the duration of response (DOR) of tusamitamab ravtansine as compared with docetaxel

Research Team

Clinical Sciences & Operations

Principal Investigator

Sanofi

Eligibility Criteria

This trial is for adults with non-squamous NSCLC that has spread, who have already tried platinum-based chemo and immune checkpoint inhibitors. They must have a certain level of CEACAM5 in their tumors and be generally healthy enough to participate (ECOG 0-1). Women and men agree to use effective birth control during the study.

Inclusion Criteria

I am a man and agree to use effective birth control during and for 6 months after the study.

I have at least one tumor that can be measured.

I agree to use effective birth control during and for 7 months after the study.

Exclusion Criteria

I haven't had any cancer other than skin or cervical pre-cancers in the last 3 years.

I have brain metastases that are either untreated or not worsening after treatment.

I have no lasting side effects from previous treatments, except for hair loss, skin color changes, or thyroid issues treated with hormones.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive either tusamitamab ravtansine or docetaxel until progression or unacceptable toxicity

6.5 months for tusamitamab ravtansine, 4 months for docetaxel

Every 2 weeks for tusamitamab ravtansine, every 3 weeks for docetaxel

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 months for tusamitamab ravtansine, 4 months for docetaxel

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

Up to 189 weeks

Treatment Details

Interventions

• Docetaxel
• tusamitamab ravtansine

Trial Overview The trial tests if tusamitamab ravtansine can improve survival without cancer growth (PFS) or overall survival (OS) better than docetaxel in patients with specific protein levels on their lung cancer cells. It also looks at response rates, quality of life, safety, and how long the response lasts.

Participant Groups

Group I: SAR408701 (tusamitamab ravtansine) Experimental Treatment 1 Intervention

Participants received tusamitamab ravtansine 100 milligrams per square meter (mg/m\^2) by intravenous (IV) infusion, once every 2 weeks (Q2W) until objective progressive disease (PD), unacceptable adverse event/toxicity, upon participant's request to stop treatment, or Investigator decision, whichever occurred first (maximum exposure: 147 weeks).

Group II: Docetaxel Active Control 1 Intervention

Participants received docetaxel 75 mg/m\^2 by IV infusion, once every 3 weeks (Q3W) until objective PD, unacceptable adverse event/toxicity, upon participant's request to stop treatment, or Investigator decision, whichever occurred first (maximum exposure: 115 weeks).

Docetaxel is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in European Union as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Canada as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Japan as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Who Is Running the Clinical Trial?

Sanofi

Lead Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Findings from Research

Docetaxel is a highly effective treatment for advanced non-small-cell lung cancer (NSCLC), showing improved patient quality of life compared to vinorelbine-cisplatin in clinical trials, leading to its FDA approval for this indication.

With a higher binding affinity for beta tubulin than paclitaxel, docetaxel is the only chemotherapy agent approved for both first- and second-line therapy of advanced NSCLC, demonstrating its versatility and efficacy in various treatment settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of docetaxel in advanced non-small-cell lung cancer. Belani, CP., Eckardt, J.[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 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 has shown impressive efficacy in treating various cancers, including breast cancer, non-small-cell lung cancer (NSCLC), and ovarian cancer, outperforming or matching established chemotherapy regimens in phase III trials involving multiple tumor types.

In addition to its effectiveness, docetaxel is often associated with an improved safety profile, and it has demonstrated a survival benefit in previously challenging cases, such as anthracycline-resistant breast cancer and second-line NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The current status of docetaxel in solid tumors. An M. D. Anderson Cancer Center Review. Hong, WK.[2018]

The combination of docetaxel and cisplatin showed a higher overall response rate in treating non-small-cell lung cancer compared to docetaxel alone, based on a meta-analysis of nine clinical trials involving 1257 patients.

However, this combination therapy also led to a higher incidence of adverse effects, including anemia and nausea, without improving the one-year survival rate compared to docetaxel alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel versus docetaxel plus cisplatin for non-small-cell lung cancer: a meta-analysis of randomized clinical trials. Li, A., Wei, ZJ., Ding, H., et al.[2018]

Docetaxel is effective in treating non-small cell lung cancer (NSCLC) by promoting microtubule assembly, leading to cell cycle arrest and death, and has shown survival benefits in both first- and second-line treatments.

The primary toxicity associated with docetaxel is neutropenia, which can be managed with weekly dosing, while other side effects like peripheral edema and interstitial pneumonitis can be mitigated with premedication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel in the treatment of non-small cell lung carcinoma: an update and analysis. Gubens, MA., Wakelee, HA.[2020]

Docetaxel is an effective chemotherapy drug that works by binding to microtubules, leading to cell-cycle arrest and apoptosis, and is approved for various cancers including breast, lung, prostate, and recently advanced gastric cancer.

While docetaxel can cause severe neutropenia as a major side effect, alternative dosing schedules have been developed to reduce this toxicity, making it safer for patients with compromised bone marrow.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel: a tubulin-stabilizing agent approved for the management of several solid tumors. Ramaswamy, B., Puhalla, S.[2018]

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]

In a study of 829 patients with previously treated non-small-cell lung cancer, oral topotecan demonstrated noninferiority to intravenous docetaxel in terms of 1-year survival rates, with 25.1% for topotecan compared to 28.7% for docetaxel.

Both treatments had different safety profiles; docetaxel was associated with higher rates of severe neutropenia (60% vs. 50%), while topotecan led to more cases of severe anemia and thrombocytopenia (26% vs. 10% and 26% vs. 7%, respectively).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III study comparing oral topotecan to intravenous docetaxel in patients with pretreated advanced non-small-cell lung cancer. Ramlau, R., Gervais, R., Krzakowski, M., et al.[2018]

Docetaxel is an effective treatment for advanced non-small cell lung cancer (NSCLC), showing improved overall survival compared to best supportive care in both first- and second-line therapies, based on randomized trials.

When combined with gemcitabine, docetaxel resulted in similar efficacy to combinations with cisplatin but caused significantly fewer severe side effects, making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The current status of docetaxel for advanced non-small cell lung cancer. Green, MR.[2018]

The combination of docetaxel (DTX) and irinotecan (CPT-11) can be safely administered biweekly to patients with advanced breast cancer (BC) and non-small-cell lung cancer (NSCLC), with dose escalation reaching 80 mg/m² for DTX and 100 mg/m² for CPT-11 supported by filgrastim.

The treatment showed promising efficacy, with an overall response rate of 51% across 41 patients, including a 59% response rate in BC patients and a 36% response rate in NSCLC patients, indicating potential for further phase II studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biweekly docetaxel-irinotecan with filgrastim support in pretreated breast and non-small-cell lung cancer patients. A phase I study. Frasci, G., Comella, P., Thomas, R., et al.[2018]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Development of docetaxel in advanced non-small-cell lung cancer. [2022]

2. England pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

Docetaxel: meeting the challenge of non-small cell lung cancer management. [2019]

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

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

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

The current status of docetaxel in solid tumors. An M. D. Anderson Cancer Center Review. [2018]

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

Docetaxel versus docetaxel plus cisplatin for non-small-cell lung cancer: a meta-analysis of randomized clinical trials. [2018]

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

Docetaxel in the treatment of non-small cell lung carcinoma: an update and analysis. [2020]

8. Spain pubmed.ncbi.nlm.nih.gov

Docetaxel: a tubulin-stabilizing agent approved for the management of several solid tumors. [2018]

9. 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]

10. Germany pubmed.ncbi.nlm.nih.gov

Administration of docetaxel plus ramucirumab with primary prophylactic pegylated-granulocyte colony-stimulating factor for pretreated non-small cell lung cancer: a phase II study. [2023]

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

Phase III study comparing oral topotecan to intravenous docetaxel in patients with pretreated advanced non-small-cell lung cancer. [2018]

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

The current status of docetaxel for advanced non-small cell lung cancer. [2018]

13. Germany pubmed.ncbi.nlm.nih.gov

Biweekly docetaxel-irinotecan with filgrastim support in pretreated breast and non-small-cell lung cancer patients. A phase I study. [2018]