Sitravatinib + Nivolumab for Advanced Non-Small Cell Lung Cancer

(SAPPHIRE Trial)

Recruiting at 579 trial locations

Overseen By Mirati Therapeutics Study Locator Services

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Mirati Therapeutics Inc.

Disqualifiers: Brain metastases, EGFR mutations, 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: Up to 44 months

577 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will compare the efficacy of the investigational agent sitravatinib in combination with nivolumab versus docetaxel in patients with advanced non-squamous NSCLC who have previously experienced disease progression on or after platinum-based chemotherapy and checkpoint inhibitor therapy.

Will I have to stop taking my current medications?

The trial information does not specify if 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 drugs Sitravatinib and Nivolumab for advanced non-small cell lung cancer?

Nivolumab has been shown to improve overall survival in patients with advanced non-small cell lung cancer (NSCLC) who have already received chemotherapy, and it is better tolerated than docetaxel. Docetaxel, when used alone or in combination with other drugs, has also been effective in improving survival rates in NSCLC patients. ^{1 2 3 4 5}

What safety data exists for treatments involving docetaxel in non-small cell lung cancer?

Docetaxel has been studied in various trials for non-small cell lung cancer, often in combination with other drugs. These studies generally focus on its effectiveness and safety, noting that it can cause side effects, but it is considered safe enough to be used in these trials. ^{2 6 7 8 9}

What makes the drug combination of Sitravatinib, Nivolumab, and Docetaxel unique for treating advanced non-small cell lung cancer?

This drug combination is unique because it combines Sitravatinib, which may target tumor growth and immune escape, with Nivolumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, and Docetaxel, a chemotherapy drug. This multi-faceted approach aims to enhance treatment effectiveness by addressing different aspects of cancer progression. ^{2 3 10 11 12}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for adults with advanced non-squamous NSCLC who've had disease progression after platinum-based chemo and checkpoint inhibitor therapy. They should have tried one or two treatments before, but not more, and can't have uncontrolled brain metastases or certain genetic mutations.

Inclusion Criteria

I have been treated with both PD-1/PD-L1 inhibitors and platinum-based chemotherapy.

My cancer progressed after treatment with a checkpoint inhibitor.

I've had 1 or 2 treatments for my advanced illness.

Exclusion Criteria

I've had cancer treatment after immunotherapy, not including maintenance chemo.

My tumor is positive for EGFR, ROS1, ALK mutations, or ALK fusions.

I have brain metastases that are not currently under control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either sitravatinib in combination with nivolumab or docetaxel

Up to 44 months

Every 2-4 weeks for nivolumab, every 3 weeks for docetaxel

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 38 months

Long-term Follow-up

Participants are monitored for overall survival and other long-term outcomes

Up to 44 months

Treatment Details

Interventions

• Docetaxel
• Nivolumab
• Sitravatinib

Trial Overview The study tests sitravatinib combined with nivolumab against docetaxel in patients whose lung cancer worsened despite previous therapies. It aims to see if the new combination is more effective than the standard treatment of docetaxel alone.

Participant Groups

Group I: Nivolumab and Sitravatinib Experimental Treatment 2 Interventions

Nivolumab will be administered by intravenous infusion over 30 minutes at 240 mg every 2 weeks or at 480 mg every 4 weeks. Sitravatinib capsules will be administered orally, once daily.

Group II: Docetaxel Active Control 1 Intervention

Docetaxel will be administered by intravenous infusion at 75 mg/m2 over 1 hour every 3 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?

Mirati Therapeutics Inc.

Lead Sponsor

Trials

73

Recruited

8,900+

Dr. Charles M. Baum

Mirati Therapeutics Inc.

Chief Executive Officer since 2023

MD, PhD

Dr. Joseph Leveque

Mirati Therapeutics Inc.

Chief Medical Officer since 2021

MD

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Findings from Research

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]

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]

Nivolumab (Opdivo) significantly improves overall survival and response rates in previously-treated patients with advanced nonsquamous non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CheckMate 057 trial.

Nivolumab has a manageable adverse event profile and is better tolerated than docetaxel, making it a valuable treatment option for patients who have progressed after chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. Keating, GM.[2018]

In a phase 3 trial involving 423 patients with untreated stage IV or recurrent non-small-cell lung cancer (NSCLC) and PD-L1 expression of 5% or more, nivolumab did not show a significant improvement in progression-free survival compared to chemotherapy, with median times of 4.2 months versus 5.9 months, respectively.

Nivolumab demonstrated a better safety profile than chemotherapy, with 71% of patients experiencing treatment-related adverse events compared to 92% in the chemotherapy group, and significantly fewer severe adverse events (grade 3 or 4) at 18% versus 51%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer. Carbone, DP., Reck, M., Paz-Ares, L., et al.[2022]

In a real-world study of 371 patients with advanced squamous non-small cell lung cancer (NSCLC) receiving nivolumab, the objective response rate was 18% and the median overall survival was 7.9 months, indicating that nivolumab is effective in this patient population.

The safety profile of nivolumab was favorable, with only 29% of patients experiencing any-grade adverse events and no treatment-related deaths, suggesting that its use in routine clinical practice aligns with findings from controlled clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Italian Cohort of Nivolumab Expanded Access Program in Squamous Non-Small Cell Lung Cancer: Results from a Real-World Population. Crinò, L., Bidoli, P., Delmonte, A., et al.[2020]

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]

In a phase II study involving 44 patients with advanced non-small-cell lung cancer resistant to platinum chemotherapy, docetaxel showed a 21% partial response rate, indicating its efficacy in this challenging patient population.

The treatment was associated with significant side effects, particularly grade 3/4 neutropenia in 85% of patients, along with hypersensitivity reactions and fluid retention, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of docetaxel for advanced or metastatic platinum-refractory non-small-cell lung cancer. Fossella, FV., Lee, JS., Shin, DM., et al.[2018]

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]

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 phase 3 study involving 272 patients with advanced squamous-cell non-small-cell lung cancer, nivolumab significantly improved overall survival (9.2 months) compared to docetaxel (6.0 months), with a 41% lower risk of death.

Nivolumab also had a better safety profile, with only 7% of patients experiencing severe treatment-related adverse events, compared to 55% in the docetaxel group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. Brahmer, J., Reckamp, KL., Baas, P., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. 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]

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

Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. [2018]

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

First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer. [2022]

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

Italian Cohort of Nivolumab Expanded Access Program in Squamous Non-Small Cell Lung Cancer: Results from a Real-World Population. [2020]

6. 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]

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

Phase II study of docetaxel for advanced or metastatic platinum-refractory non-small-cell lung cancer. [2018]

8. Germany pubmed.ncbi.nlm.nih.gov

Sunitinib in combination with docetaxel in patients with advanced solid tumors: a phase I dose-escalation study. [2021]

9. 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]

10. 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]

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

SELECT-2: a phase II, double-blind, randomized, placebo-controlled study to assess the efficacy of selumetinib plus docetaxel as a second-line treatment of patients with advanced or metastatic non-small-cell lung cancer. [2022]

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

Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. [2022]