Sitravatinib + Nivolumab for Advanced Non-Small Cell Lung Cancer

(SAPPHIRE Trial)

No longer recruiting at 609 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for individuals with advanced non-squamous non-small cell lung cancer (NSCLC). It compares the effectiveness of sitravatinib and nivolumab (Opdivo) against the standard treatment, docetaxel. This trial targets patients whose cancer has progressed after both platinum-based chemotherapy and checkpoint inhibitor therapy. Those who have undergone one or two treatment plans and can take docetaxel may be suitable candidates. The goal is to determine if the new combination more effectively slows cancer progression. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering patients an opportunity to contribute to groundbreaking research.

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.

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

A previous study tested the combination of sitravatinib and nivolumab for safety and effectiveness in patients with advanced cancer. The results showed that most participants tolerated the treatment well. The side effects resembled those of similar treatments and were generally manageable.

No new serious safety issues emerged, which is encouraging. This indicates that the combination has been tested in people before without unexpected problems. Overall, past research suggests the treatment is safe, but individual reactions can vary. Prospective participants should discuss any concerns with their doctor to determine if joining a trial is appropriate. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of sitravatinib and nivolumab for advanced non-small cell lung cancer because it offers a novel approach to treatment. Unlike standard chemotherapy options like docetaxel, this combination targets cancer cells in two unique ways: nivolumab boosts the immune system's ability to recognize and attack cancer cells, while sitravatinib inhibits specific proteins that help tumors grow and evade the immune system. This dual mechanism of action has the potential to enhance treatment effectiveness and provide a promising alternative for patients who have not responded to traditional therapies.

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

Research has shown that sitravatinib combined with nivolumab, which participants in this trial may receive, may help treat advanced non-small cell lung cancer (NSCLC). Studies found that this combination can shrink tumors and improve survival for patients previously treated with checkpoint inhibitors and chemotherapy. However, it did not achieve its main goal of increasing overall survival compared to the standard treatment, docetaxel, which is another option in this trial. While there are positive signs, the combination might not be more effective than existing options. Overall, the data shows mixed results, with some potential benefits but not surpassing current treatments in overall survival. ^{1 2 3 4 6}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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 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 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]

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]

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]

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]

Citations

1. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)04019-X/fulltext

SAPPHIRE: phase III study of sitravatinib plus nivolumab ... Phase III study of sitravatinib plus nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03906071

NCT03906071 | Phase 3 Study of Sitravatinib Plus ... This study will compare the efficacy of the investigational agent sitravatinib in combination with nivolumab versus docetaxel in patients with ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10330304/

MRTX-500 Phase 2 Trial: Sitravatinib With Nivolumab in ... Although ORR was not met, this combination exhibited antitumor activity and encouraged survival in CPI-experienced patients with nonsquamous NSCLC. Keywords: ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S092375342304019X

phase III study of sitravatinib plus nivolumab versus ... The study evaluated whether CPI resistance can be overcome in patients treated with platinum-based chemotherapy and CPI.

5. onclive.com onclive.com/view/sitravatinib-plus-nivolumab-fails-to-meet-os-end-point-in-nonsquamous-nsclc

Sitravatinib Plus Nivolumab Fails to Meet OS End Point in ... The combination of sitravatinib and nivolumab did not meet the primary end point of overall survival compared with docetaxel as second- or third-line treatment.

6. kucancercenter.org kucancercenter.org/cancer-clinical-trials/find-trial/clinical-trial-results/nct03906071

A Randomized Phase III Study of Sitravatinib in ... A Randomized Phase III Study of Sitravatinib in Combination with Nivolumab Versus Docetaxel in Patients with Advanced Non-Squamous Non-Small Cell Lung ...