Sutetinib for Non-Small Cell Lung Cancer

Recruiting at 6 trial locations

Overseen By Dawei Zhang

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Teligene US

Must not be taking: EGFR-TKIs, Chemotherapy

Disqualifiers: Active CNS metastases, Uncontrolled infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

66 Participants Needed

Trial Summary

What is the purpose of this trial?

The main objective of the study will be to evaluate the efficacy of sutetinib maleate capsules in participants with locally advanced or metastatic non-small cell lung cancer NSCLC (uncommon EGFR mutations only).

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before joining. You must not have used any systemic anti-tumor therapy, including chemotherapy or radiation, within 3 weeks before enrolling. Additionally, you should avoid drugs or foods that affect the enzyme CYP3A4 within 14 days before starting the trial.

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

Research shows that sunitinib malate, a component of Sutetinib, has shown promising activity in treating advanced non-small cell lung cancer (NSCLC) with a 10% response rate in patients who had previously undergone chemotherapy. This suggests that Sutetinib may have potential benefits for NSCLC patients. ^{1 2 3 4 5}

Is sunitinib safe for humans?

Sunitinib, also known as Sutent, has been studied for safety in various conditions and has shown a good safety profile in healthy subjects and patients with different types of cancer, including gastrointestinal stromal tumors and renal cell carcinoma. ^{1 5 6 7 8}

How is the drug Sutetinib different from other treatments for non-small cell lung cancer?

Sutetinib (Sunitinib Malate) is unique because it is a multi-targeted drug that inhibits several key pathways involved in tumor growth, such as VEGF and PDGF receptors, and is given on a specific schedule of 4 weeks on treatment followed by 2 weeks off. This approach is different from many standard treatments for non-small cell lung cancer, which may not target multiple pathways or follow this specific dosing schedule. ^{1 5 8 9 10}

Eligibility Criteria

Adults with advanced or metastatic non-small cell lung cancer (NSCLC) that have uncommon EGFR mutations can join. They should have at least one measurable tumor, good organ function, an ECOG score of 0-2, and a life expectancy over 3 months. People who've had certain treatments recently or have active infections, brain metastases, trouble swallowing pills, or use drugs affecting CYP3A4 can't participate.

Inclusion Criteria

My lung cancer is confirmed to be advanced or has spread.

My tumor has a rare EGFR mutation.

My blood, liver, kidney, and clotting tests are within normal ranges.

Exclusion Criteria

I cannot swallow pills or have chronic stomach issues affecting food absorption.

I do not have any uncontrolled infections.

I have no side effects from previous treatments above mild, except for hair loss.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sutetinib maleate capsules orally for 28-day cycles

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Sutetinib Maleate Capsule

Trial Overview The trial is testing Sutetinib Maleate Capsules to see how effective they are for NSCLC patients with specific genetic changes in their tumors. It's focused on those who haven't used certain other cancer drugs before.

Participant Groups

Group I: Single arm, Open label Experimental Treatment 1 Intervention

Participants will receive sutetinib maleate capsule taken orally with (preferred) or without food, at the dose directed by the Investigators, 28 days for a cycle.

Sutetinib Maleate Capsule is already approved in United States, European Union for the following indications:

Approved in United States as Sutent for:

• Gastrointestinal Stromal Tumor (GIST)
• Renal Cell Carcinoma (RCC)
• Pancreatic Neuroendocrine Tumors (pNET)

Approved in European Union as Sutent for:

• Gastrointestinal Stromal Tumors (GIST)
• Renal Cell Carcinoma (RCC)
• Pancreatic Neuroendocrine Tumors (pNET)

Who Is Running the Clinical Trial?

Teligene US

Lead Sponsor

Trials

3

Recruited

230+

Findings from Research

In a phase II study involving 47 patients with advanced non-small cell lung cancer (NSCLC), sunitinib showed a low objective response rate of 2.1%, but 23.4% of patients experienced stable disease for at least 8 weeks, indicating some potential for disease control.

The treatment was generally well tolerated, with a median progression-free survival of 11.9 weeks and a median overall survival of 37.1 weeks, suggesting that sunitinib may be a viable option for patients who have not responded to platinum-based chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of continuous daily sunitinib dosing in patients with previously treated advanced non-small cell lung cancer. Novello, S., Scagliotti, GV., Rosell, R., et al.[2021]

In a phase II study involving 75 patients with non-small cell lung cancer (NSCLC), maintenance treatment with vandetanib after chemotherapy showed a progression-free survival (PFS) rate of 44.4% at 3 months, which supports its efficacy compared to a placebo.

Vandetanib was generally well tolerated, with common side effects including rash (77.3%) and diarrhea (60.0%), indicating a manageable safety profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, phase II study of vandetanib maintenance for advanced or metastatic non-small-cell lung cancer following first-line platinum-doublet chemotherapy. Ahn, JS., Lee, KH., Sun, JM., et al.[2022]

Sunitinib malate, a multitargeted tyrosine kinase inhibitor, showed an objective response rate of 11.1% in 63 patients with previously treated advanced non-small-cell lung cancer (NSCLC), indicating some effectiveness as a treatment option.

The treatment was generally well tolerated, with a median progression-free survival of 12 weeks and median overall survival of 23.4 weeks, suggesting that sunitinib has a favorable safety profile and potential for further investigation in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter, phase II trial of sunitinib in previously treated, advanced non-small-cell lung cancer. Socinski, MA., Novello, S., Brahmer, JR., et al.[2022]

Sunitinib (Sutent) is an effective treatment for metastatic renal cell carcinoma (RCC), showing a 37% response rate and 48% stable disease, making it the preferred first-line therapy for this cancer.

Sunitinib also demonstrates efficacy in gastrointestinal stromal tumors (GIST) with an 8% response rate and 70% stable disease, contributing to a median survival of 20 months, and shows moderate activity in breast cancer and non-small cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma and various other solid tumors. Polyzos, A.[2018]

Sunitinib effectively inhibits the growth and migration of papillary thyroid cancer cells with the RET/PTC1 rearrangement, demonstrating a dose-dependent effect with a mean lethal concentration of 1.81 microM.

The drug works by blocking specific signaling pathways (MEK/ERK and SAPK/JNK), leading to cell cycle arrest and increased expression of the sodium/iodide symporter (NIS), which is important for iodide metabolism in thyroid cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sunitinib inhibits MEK/ERK and SAPK/JNK pathways and increases sodium/iodide symporter expression in papillary thyroid cancer. Fenton, MS., Marion, KM., Salem, AK., et al.[2018]

Sunitinib malate (Sutent) was approved by the FDA for treating gastrointestinal stromal tumors (GIST) after patients showed disease progression or intolerance to imatinib, demonstrating a median time-to-tumor progression of 27.3 weeks compared to 6.4 weeks for placebo.

In advanced renal cell carcinoma, sunitinib showed partial response rates of 25.5% and 36.5% in two studies, with median response durations of 27.1 and 54 weeks, although it was associated with common side effects like diarrhea and hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approval summary: sunitinib for the treatment of imatinib refractory or intolerant gastrointestinal stromal tumors and advanced renal cell carcinoma. Goodman, VL., Rock, EP., Dagher, R., et al.[2022]

A phase-I clinical trial involving 48 healthy Chinese subjects demonstrated that the generic version of sunitinib is bioequivalent to the original Sutent®, with pharmacokinetic parameters falling within the acceptable range for bioequivalence.

Both sunitinib and Sutent® exhibited comparable safety profiles, supporting the use of generic sunitinib as a viable alternative treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of sunitinib and Sutent® in Chinese healthy subjects: an open-label, randomized, crossover study. Wang, Y., Deng, Q., Gao, Z., et al.[2023]

Sunitinib malate is a multi-kinase inhibitor approved for treating advanced renal cell carcinoma and other specific tumors, showing modest antitumor activity in ovarian cancer based on Phase I and II trials.

The drug has an acceptable safety profile, but further research is needed to better understand its toxicity and to explore combination therapies for enhanced efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential of sunitinib as a therapy in ovarian cancer. Leone Roberti Maggiore, U., Valenzano Menada, M., Venturini, PL., et al.[2018]

Sunitinib malate demonstrated a strong anti-tumor effect against human bladder cancer cell lines, showing a dose- and time-dependent response similar to conventional drugs like cisplatin and gemcitabine.

The study found that sunitinib can synergistically enhance the effectiveness of gemcitabine, indicating a potential for combined therapy in treating bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sunitinib malate synergistically potentiates anti-tumor effect of gemcitabine in human bladder cancer cells. Yoon, CY., Lee, JS., Kim, BS., et al.[2021]

Sunitinib malate is a small molecule kinase inhibitor effective against various tyrosine kinase receptors and has recently been approved for treating advanced pancreatic neuroendocrine tumors, in addition to its existing approvals for renal cell carcinoma and gastrointestinal stromal tumors.

The use of sunitinib in treating rare tumors like peripheral primitive neuroectodermal tumor (pPNET), paraganglioma (PGL), and epithelioid hemangioendothelioma (EHE) is promising due to these tumors' overexpression of pro-angiogenic factors, suggesting that sunitinib may help manage these difficult-to-treat conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting VEGF-VEGFR Pathway by Sunitinib in Peripheral Primitive Neuroectodermal Tumor, Paraganglioma and Epithelioid Hemangioendothelioma: Three Case Reports. Prochilo, T., Savelli, G., Bertocchi, P., et al.[2022]

References

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

Phase II study of continuous daily sunitinib dosing in patients with previously treated advanced non-small cell lung cancer. [2021]

2. Ireland pubmed.ncbi.nlm.nih.gov

A randomized, phase II study of vandetanib maintenance for advanced or metastatic non-small-cell lung cancer following first-line platinum-doublet chemotherapy. [2022]

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

Multicenter, phase II trial of sunitinib in previously treated, advanced non-small-cell lung cancer. [2022]

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

Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma and various other solid tumors. [2018]

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

Sunitinib inhibits MEK/ERK and SAPK/JNK pathways and increases sodium/iodide symporter expression in papillary thyroid cancer. [2018]

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

Approval summary: sunitinib for the treatment of imatinib refractory or intolerant gastrointestinal stromal tumors and advanced renal cell carcinoma. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of sunitinib and Sutent® in Chinese healthy subjects: an open-label, randomized, crossover study. [2023]

8. England pubmed.ncbi.nlm.nih.gov

The potential of sunitinib as a therapy in ovarian cancer. [2018]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

Sunitinib malate synergistically potentiates anti-tumor effect of gemcitabine in human bladder cancer cells. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Targeting VEGF-VEGFR Pathway by Sunitinib in Peripheral Primitive Neuroectodermal Tumor, Paraganglioma and Epithelioid Hemangioendothelioma: Three Case Reports. [2022]