SAR408701 vs Docetaxel for Non-Small Cell Lung Cancer

(CARMEN-LC03 Trial)

Recruiting at 761 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new treatment, tusamitamab ravtansine, to determine if it helps people with advanced non-small cell lung cancer live longer or delay cancer progression. It compares this treatment to an existing chemotherapy drug, docetaxel. Suitable participants have non-squamous lung cancer that has spread, have previously undergone chemotherapy and immune therapy, and have a specific protein (CEACAM5) in their cancer cells. The trial also evaluates whether the new treatment improves quality of life and assesses its safety. As a Phase 3 trial, this study serves as the final step before FDA approval, offering patients access to a potentially groundbreaking treatment.

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.

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

Research has shown that tusamitamab ravtansine is generally safe for patients with non-small cell lung cancer (NSCLC). In studies, most patients tolerated the treatment well. Some experienced side effects, but these were usually manageable. Overall, previous research found tusamitamab ravtansine effective and safe, making it a promising option for those considering participation in a clinical trial for this treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lung cancer?

Unlike the standard treatments for non-small cell lung cancer, such as chemotherapy with drugs like docetaxel, tusamitamab ravtansine offers a unique approach. This experimental drug is an antibody-drug conjugate, which means it combines an antibody with a potent anti-cancer drug. The antibody targets a specific protein on cancer cells, delivering the drug directly to the tumor, potentially increasing effectiveness while minimizing damage to healthy cells. Researchers are excited about tusamitamab ravtansine because it could offer a more targeted and less toxic treatment option for patients.

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

This trial will compare tusamitamab ravtansine with Docetaxel for treating non-squamous non-small cell lung cancer (NSCLC). Studies have shown that tusamitamab ravtansine holds promise for this type of lung cancer. Research indicates that it is generally safe and can fight tumors, especially in patients whose tumors have high levels of a protein called CEACAM5. In earlier studies, patients who received tusamitamab ravtansine experienced tumor shrinkage or halted growth. This treatment targets cancer cells directly, delivering cancer-fighting drugs to them, which may benefit patients who have already tried standard chemotherapy and immunotherapy. Overall, early findings suggest that tusamitamab ravtansine could be an effective option for this type of lung cancer. ^{1 2 4 6 7}

Who Is on the Research Team?

Clinical Sciences & Operations

Principal Investigator

Sanofi

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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]

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 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 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]

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]

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]

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 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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.9039

Safety and efficacy of tusamitamab ravtansine ... Safety and efficacy of tusamitamab ravtansine (SAR408701) in long-term treated patients with nonsquamous non–small cell lung cancer (NSQ NSCLC) ...

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02887-4/fulltext

1311P Phase II, open-label study of frontline tusamitamab ... Phase II, open-label study of frontline tusamitamab ravtansine with pembrolizumab ± chemotherapy in advanced non-squamous non-small cell lung cancer

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12296879/

Phase 1 study evaluating safety and pharmacokinetics of ... Tusamitamab ravtansine demonstrated a tolerable safety profile at a dose of 80–170 mg/m2 in three different administration schedules in Japanese ...

4. jtocrr.org jtocrr.org/article/S2666-3643(25)00061-X/fulltext

Evaluation of the Safety, Pharmacokinetics, and Antitumor ... Tusamitamab ravtansine demonstrated a favorable safety profile, objective responses, and antitumor activity in patients with high CEACAM5-expressing NSq NSCLC.

5. jto.org jto.org/article/S1556-0864(25)00224-2/fulltext

29P: Evaluation of tusamitamab ravtansine, a CEACAM5 ... This phase II study evaluated efficacy and safety of tusamitamab ravtansine in non-squamous NSCLC participants with high baseline circulating ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S266636432500061X

Evaluation of the safety, pharmacokinetics, and antitumor ... Tusamitamab ravtansine demonstrated a favorable safety profile, objective responses, and antitumor activity in patients with high CEACAM5-expressing NSq NSCLC.

7. asco.org asco.org/videos-slides/VIDEOSANDSLIDES212850

Safety and efficacy of tusamitamab ravtansine ... Safety and efficacy of tusamitamab ravtansine (SAR408701) in long-term treated patients with nonsquamous non–small cell lung cancer (NSQ NSCLC) expressing ...