Sigvotatug Vedotin vs Docetaxel for Lung Cancer

Not currently recruiting at 530 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Seagen Inc.

Must be taking: Platinum-based chemotherapy, Anti-PD-(L)1

Must not be taking: Antimicrotubule agents

Disqualifiers: Life expectancy < 3 months, Respiratory conditions, Peripheral neuropathy, Uncontrolled diabetes, 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: Unknown

Duration: Approximately 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, sigvotatug vedotin, to determine if it outperforms the standard treatment, docetaxel, for non-small cell lung cancer (NSCLC) that cannot be surgically removed or has metastasized. Sigvotatug vedotin is an experimental treatment designed to target and kill cancer cells, while docetaxel is a commonly used anticancer drug. The trial aims to compare the effectiveness and side effects of these treatments. It seeks participants whose lung cancer has progressed after specific prior treatments, such as platinum-based chemotherapy and anti-PD-(L)1 drugs. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have had any systemic anticancer therapy within 21 days before starting the trial.

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

Research has shown that sigvotatug vedotin, a new cancer treatment, raises some safety concerns. In one study, a patient with non-small cell lung cancer (NSCLC) died from treatment-related pneumonitis, a serious lung inflammation. However, most side effects of the treatment were manageable with proper care.

In contrast, docetaxel is a well-known cancer drug with a long history of use. It is approved for treating NSCLC and is typically given to patients who have already tried other treatments. This extensive use provides a wealth of safety information, and doctors are experienced in managing its side effects.

In this trial, researchers aim to determine if sigvotatug vedotin is more effective than docetaxel. While sigvotatug vedotin remains under investigation, docetaxel's widespread use offers some reassurance about its safety. ^{1 2 3 4 5}

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

Sigvotatug vedotin is unique because it targets lung cancer cells with a novel approach. Unlike traditional chemotherapy treatments like docetaxel, which kill fast-growing cells indiscriminately, sigvotatug vedotin uses an antibody-drug conjugate to deliver the active ingredient directly to the cancer cells. This precision targeting can potentially reduce harm to healthy cells, leading to fewer side effects and better tolerability for patients. Researchers are excited about this treatment because it represents a more tailored approach to fighting cancer, which could improve outcomes for those with lung cancer.

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

Research has shown that sigvotatug vedotin, an experimental drug tested in this trial, may effectively treat non-small cell lung cancer (NSCLC). An earlier study found that the drug shrank or eliminated tumors in nearly one in five patients. It also prevented cancer progression in many patients, achieving a 69% success rate. This drug is an antibody-drug conjugate (ADC), designed to target and kill cancer cells directly. Meanwhile, participants in the control arm will receive docetaxel, an approved treatment for NSCLC, known to work well for patients who have tried other treatments. This trial tests both drugs to determine which works better for NSCLC. ^{1 2 4 5 6}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

This trial is for adults with advanced non-small cell lung cancer (NSCLC) that's spread or can't be surgically removed. They should have had only one prior platinum-based chemo and an anti-PD-(L)1 drug, or up to two targeted therapies if they have certain genomic alterations in their tumors.

Inclusion Criteria

My condition worsened after my last treatment.

My lung cancer is at an advanced stage and cannot be surgically removed.

My lung cancer is non-squamous non-small cell type.

Exclusion Criteria

I have not had another cancer or any remaining cancer from a past diagnosis in the last 3 years.

I haven't had any cancer treatment in the last 3 weeks.

I have a specific respiratory condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either sigvotatug vedotin on Days 1 and 15 during each 28-day cycle or docetaxel on Day 1 during each 21-day cycle

Approximately 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Docetaxel
• SGN-B6A

Trial Overview The study compares sigvotatug vedotin (SGN-B6A), a new antibody drug designed to target and kill cancer cells, against docetaxel, an approved anticancer drug. Participants will receive either SGN-B6A on Days 1 and 15 of a 28-day cycle or docetaxel on Day 1 of a 21-day cycle.

How Is the Trial Designed?

Group I: Experimental Arm Experimental Treatment 1 Intervention

sigvotatug vedotin monotherapy

Group II: Control Arm Active Control 1 Intervention

Docetaxel monotherapy

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?

Seagen Inc.

Lead Sponsor

Trials

212

Recruited

73,800+

Founded

1997

Headquarters

Bothell, USA

Known For

Antibody-Drug Conjugates

Top Products

Adcetris (brentuximab vedotin), Tukysa (tucatinib), Padcev (enfortumab vedotin-ejfv), Tivdak (tisotumab vedotin-tftv)

Dr. Roger Dansey

Seagen Inc.

Chief Medical Officer since 2018

MD from University of Witwatersrand

David R. Epstein

Seagen Inc.

Chief Executive Officer since 2022

BSc in Pharmacy from Rutgers University, MBA from Columbia University

Seagen, a wholly owned subsidiary of Pfizer

Lead Sponsor

Trials

20

Recruited

4,900+

Published Research Related to This Trial

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]

In a phase III study involving 274 patients with stage IIIA or locally treatable IIIB non-small-cell lung cancer (NSCLC), neoadjuvant docetaxel treatment resulted in a median survival of 14.8 months compared to 12.6 months in the control group, indicating a potential benefit in overall survival.

Docetaxel was well-tolerated, with 77% of patients completing all planned treatment cycles, although it did cause significant side effects like grade 4 neutropenia in 55% of patients, suggesting that while effective, careful monitoring for toxicity is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel as neoadjuvant therapy for radically treatable stage III non-small-cell lung cancer: a multinational randomised phase III study. Mattson, KV., Abratt, RP., ten Velde, G., et al.[2020]

Docetaxel is a well-tolerated second-line chemotherapy for advanced non-small cell lung cancer (NSCLC) that showed a partial response in 6.3% of patients and stable disease in 25%, with a median survival time of 8.1 months.

Importantly, treatment with docetaxel did not negatively affect the overall quality of life for patients, and it helped alleviate symptoms like shortness of breath and weight loss in many cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doxetaxel in previously treated non-small cell lung cancer patients: clinical efficacy and quality of life. Sirisinha, T., Sirilertrakul, S., Jirajarus, M., et al.[2018]

In a study of 182 elderly patients (average age 76) with advanced non-small-cell lung cancer, docetaxel showed a significant improvement in progression-free survival (5.5 months) and response rates (22.7%) compared to vinorelbine (3.1 months and 9.9%, respectively).

While docetaxel did not significantly improve overall survival compared to vinorelbine, it was associated with better disease-related symptom improvement and was generally well tolerated, making it a potential option for standard treatment in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III study of docetaxel compared with vinorelbine in elderly patients with advanced non-small-cell lung cancer: results of the West Japan Thoracic Oncology Group Trial (WJTOG 9904). Kudoh, S., Takeda, K., Nakagawa, K., et al.[2022]

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 two phase III trials involving patients with previously treated non-small cell lung cancer, docetaxel at a dose of 75 mg/m2 significantly improved median survival (7.5 months) compared to best supportive care (4.6 months) and showed a higher 1-year survival rate (37% vs 11%).

Docetaxel at 75 mg/m2 also demonstrated comparable efficacy to other treatments like vinorelbine/ifosfamide, with manageable and predictable adverse events, confirming its role as an effective second-line therapy for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) shows survival and quality-of-life benefits in the second-line treatment of non-small cell lung cancer: a review of two phase III trials. Shepherd, FA., Fossella, FV., Lynch, T., et al.[2019]

In a Phase IV study involving 411 Iranian cancer patients, docetaxel (Alvotere) demonstrated an acceptable safety profile, with alopecia being the most common adverse event reported in 41.12% of patients.

The study found that 22.38% of patients experienced severe adverse events (grade 3 or 4), with a notable difference in skin disorders between genders, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Post-Marketing Surveillance Study to Evaluate the Safety Profile of Alvotere&#9415; (Docetaxel) in Iranian Patients Diagnosed with Different Types of Cancers Receiving Chemotherapy. Shahi, F., Vafaeezadeh, F., Ansarinejad, N., et al.[2022]

Docetaxel is an effective treatment for non-small-cell lung cancer, showing response rates of 21% to 38% in previously untreated patients and 20% to 21% in those who had failed prior chemotherapy, with median survival times ranging from 25.2 to 47.0 weeks.

Combining docetaxel with platinum compounds like cisplatin or carboplatin has demonstrated improved response rates (21% to 48%) and tolerability, with ongoing studies evaluating its effectiveness in advanced non-small-cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel in combination with platinums in patients with advanced non-small-cell lung cancer. Belani, CP.[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]

In two phase III trials involving patients with previously treated non-small cell lung cancer, docetaxel at a dose of 75 mg/m2 significantly improved median survival (7.5 months) compared to best supportive care (4.6 months) and showed a higher 1-year survival rate (37% vs 11%).

Docetaxel at 75 mg/m2 also demonstrated comparable efficacy to other treatments like vinorelbine/ifosfamide, with manageable and predictable adverse events, confirming its role as an effective second-line therapy for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) shows survival and quality-of-life benefits in the second-line treatment of non-small cell lung cancer: A review of two phase III trials. Shepherd, FA., Fossella, FV., Lynch, T., et al.[2019]

Citations

1. onclive.com onclive.com/view/novel-adc-sigvotatug-vedotin-generates-early-efficacy-in-nsclc

Novel ADC Sigvotatug Vedotin Generates Early Efficacy in ... Findings from the phase 1 SGNB6A-001 trial (NCT04389632) revealed that sigvotatug vedotin led to a confirmed overall response rate (ORR) of 19.0 ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.8521

Efficacy and safety of sigvotatug vedotin, an investigational ... The most common ≥G3 TEAEs in pts with NSCLC were dyspnea (9.7%), fatigue (7.1%), and neutropenia (5.3%). One pt with NSCLC had a treatment- ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02972-7/fulltext

1398TiP Be6A Lung-01, a phase III study of sigvotatug ... Integrin beta-6 (IB6) expression is correlated with poor outcomes in several cancers, including NSCLC, and >90% of NSCLC tumors express IB6. ... SV (formerly ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04389632

A Study of Sigvotatug Vedotin in Advanced Solid Tumors This trial will look at a drug called sigvotatug vedotin (SGN-B6A) alone and with pembrolizumab, with or without chemotherapy, to find out whether it is safe ...

5. onclive.com onclive.com/view/phase-3-evaluation-of-sigvotatug-vedotin-is-underway-in-pretreated-nonsquamous-nsclc

Phase 3 Evaluation of Sigvotatug Vedotin Is Underway in ... Phase 1 data showed a 19% overall response rate and 69% disease control rate in heavily pretreated NSCLC patients, with promising results in ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.3010

Sigvotatug vedotin (SV), an investigational integrin beta-6 ... Conclusions: SV+P demonstrated manageable safety and encouraging preliminary efficacy. These data support the ongoing phase 3 Be6A-Lung-02 study ...