APL-101 for Lung Cancer

(SPARTA Trial)

Recruiting at 117 trial locations

Overseen By Emma (Xiaoning) Cai

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Apollomics Inc.

Must be taking: EGFR inhibitors

Must not be taking: QTc risk drugs

Disqualifiers: Uncontrolled infection, Heart disease, 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

Compensation: Varies

Number of Visits: 1

Duration: Approximately 2 years

497 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called APL-101 (also known as Vebreltinib) for individuals with certain types of lung cancer and other solid tumors. The main goal is to evaluate the effectiveness of APL-101 alone and in combination with EGFR inhibitors, which are common cancer drugs. The trial specifically targets patients with genetic changes in their tumors, such as MET alterations or EGFR mutations. It may suit those with advanced lung cancer or other solid tumors who have developed resistance to standard treatments. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop taking medications with known QTc risk and strong CYP3A4 inducers or inhibitors at least 5 half-lives before starting the study drug. If these medications can be safely replaced with alternatives, you may still qualify for the trial.

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

Research has shown that APL-101, also known as vebreltinib, was safe in earlier studies. Patients with METex14-mutant non-small cell lung cancer (NSCLC) tolerated the treatment well. These studies indicate that vebreltinib is effective and generally safe for both new patients and those previously treated. While side effects can occur, they have not outweighed the potential benefits observed in these trials. Overall, evidence suggests that APL-101 is well-tolerated in patients with certain lung cancer mutations. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about APL-101 because it targets MET alterations, which are genetic changes involved in some lung cancers. Unlike standard treatments that may not specifically target MET, APL-101 is designed to hone in on this particular alteration, potentially offering a more precise attack on cancer cells. Additionally, APL-101 is administered as oral capsules, which can be more convenient for patients compared to traditional intravenous chemotherapy. This targeted approach could lead to improved outcomes for patients whose cancers are driven by MET alterations, making it a promising option in the fight against lung cancer.

What evidence suggests that APL-101 could be an effective treatment for lung cancer?

Studies have shown that APL-101, also known as vebreltinib, effectively treats non-small cell lung cancer (NSCLC) with specific genetic changes. In this trial, participants with a mutation called MET exon 14 will receive APL-101. Research indicates that these patients have responded positively to the treatment. Specifically, about 67% of patients experienced tumor shrinkage, known as the objective response rate (ORR). APL-101 targets the MET gene, which can drive cancer growth, and this targeted approach helps control the disease. The treatment has also been found to be generally safe for patients. Overall, APL-101 shows promise for patients with certain genetic profiles in lung cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Mythili Sangem

Principal Investigator

Apollomics Inc.

Are You a Good Fit for This Trial?

Adults with various cancers, including lung cancer with specific genetic changes (c-Met EXON 14 skip mutations), who have acceptable organ function and a life expectancy of at least 3 months. They must not be planning major surgery soon, can provide a tumor sample, and women should not be pregnant. People with uncontrolled infections or certain other health conditions are excluded.

Inclusion Criteria

Patients meeting specific criteria for each of the 9 cohorts (A1, A2, B, C, C1, C2, D, E, F)

I have brain or spinal cord disease that doesn’t cause symptoms.

My organs are functioning well.

Exclusion Criteria

Use or intended use of any other investigational product, including herbal medications, through Study Treatment Termination

I currently have an active COVID-19 infection.

I have hepatitis or HIV but am not stable on medication, or I am stable with HIV and meet specific health criteria.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive APL-101 as monotherapy or in combination with EGFR inhibitors, depending on cohort assignment

Approximately 2 years

1 cycle = 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 2 years

Long-term follow-up

Participants are monitored for progression-free survival and overall survival

Approximately 3 years

What Are the Treatments Tested in This Trial?

Interventions

• APL-101

Trial Overview APL-101 Oral Capsules are being tested for their effectiveness as both a standalone treatment and an add-on therapy to EGFR inhibitors in patients with non-small cell lung cancer (NSCLC) and other solid tumors that show specific genetic alterations related to the MET gene.

How Is the Trial Designed?

Group I: Primary CNS tumors with MET alterations Experimental Treatment 1 Intervention

Cohort E: APL-101 Oral Capsules

Group II: NSCLC MET amplification and EGFR wild-type Experimental Treatment 1 Intervention

Cohort C-1: APL-101 Oral Capsules

Group III: NSCLC Exon 14 Skip Treatment Naive Experimental Treatment 1 Intervention

Cohort A-1: APL-101 Oral Capsules

Group IV: NSCLC Exon 14 Skip Previously Treated Experimental Treatment 1 Intervention

Cohort A-2: APL-101 Oral Capsules

Group V: NSCLC Exon 14 MET Inhibitor Experienced Experimental Treatment 1 Intervention

Cohort B: APL-101 Oral Capsules

Group VI: EGFR positive NSCLC MET amplification as an acquired resistance Experimental Treatment 1 Intervention

Cohort C-2: APL-101 Oral Capsules + Standard of Care EGFR Inhibitor

Group VII: Basket of tumor types wild-type MET with over-expression of HGF and MET Experimental Treatment 1 Intervention

Cohort F: APL-101 Oral Capsules

Group VIII: Basket of tumor types MET amplification except for primary CNS tumors Experimental Treatment 1 Intervention

Cohort C: APL-101 Oral Capsules

Group IX: Basket of solid tumor with MET gene fusions except for primary CNS tumors Experimental Treatment 1 Intervention

Cohort D: APL-101 Oral Capsules

Who Is Running the Clinical Trial?

Apollomics Inc.

Lead Sponsor

Trials

6

Recruited

750+

Published Research Related to This Trial

In a study of 80 patients with advanced non-small cell lung cancer, the combination of apatinib and chemotherapy resulted in a total effective rate of 67.5%, significantly higher than the 45% effectiveness of chemotherapy alone.

Patients receiving apatinib also experienced a greater improvement in quality of life scores and lower levels of tumor markers (CEA and CA153) after treatment, with no significant increase in adverse reactions compared to the control group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Observation on the Clinical Effect of Apatinib Combined with Chemotherapy in the Treatment of Advanced Non-Small Cell Lung Cancer. Cui, YJ., Liu, J., Liu, MM., et al.[2022]

Apatinib demonstrated a 13.2% objective response rate and a 63.2% disease control rate in 40 patients with advanced non-squamous non-small-cell lung cancer, indicating its potential efficacy as a treatment option for heavily pretreated patients.

The treatment was associated with manageable side effects, with common adverse events including hand-foot-skin reaction (30%) and proteinuria (27.5%), suggesting that apatinib can be safely administered even after disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Clinical Trial of Apatinib in Pretreated Advanced Non-squamous Non-small-cell Lung Cancer. Wu, F., Zhang, S., Xiong, A., et al.[2019]

Apatinib, a VEGFR-2 inhibitor, was found to be effective for treating advanced non-small cell lung cancer in 34 patients after chemotherapy failure, with a median progression-free survival of four months.

The treatment was generally safe, with manageable side effects like hypertension and hand-foot syndrome, and no severe adverse reactions were reported, indicating good tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apatinib monotherapy for advanced non-small cell lung cancer after the failure of chemotherapy or other targeted therapy. Liu, Z., Ou, W., Li, N., et al.[2019]

In a study of 128 patients with advanced non-small cell lung cancer (NSCLC) after first-line treatment failure, apatinib combined with chemotherapy significantly improved median progression-free survival (PFS) to 6.0 months compared to 3.7 months for chemotherapy alone.

Apatinib demonstrated good safety with a low incidence of severe adverse events (grades 3-4) across treatment regimens, and while it did not show a significant difference in PFS or overall survival (OS) when compared to chemotherapy alone, it was beneficial when combined with chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and Survival Analysis of Apatinib in Patients with Advanced Nonsquamous Non-small Cell Lung Cancer after Failure of First-line Treatment]. Wang, X., Zhang, W., Du, W., et al.[2018]

In a study of 40 patients with advanced squamous cell lung cancer, apatinib alone or in combination with chemotherapy showed a disease control rate of 72.5% and a median progression-free survival of 3.7 months, indicating promising short-term efficacy.

The treatment was generally well-tolerated, with most adverse events, such as leukopenia and hypertension, being of grade I and II severity, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term efficacy and safety of apatinib in advanced squamous cell carcinoma of the lung. Li, X., Le, L., Han, L., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.02363

Vebreltinib for Advanced Non–Small Cell Lung Cancer ... Preliminary phase I study outcomes revealed an ORR of 66.7% alongside a tolerable safety profile in patients with advanced METex14-mutant NSCLC.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39058972/

Vebreltinib for Advanced Non-Small Cell Lung Cancer ... Conclusion: Vebreltinib has shown promising efficacy and a favorable safety profile in patients with METex14-mutant NSCLC. Trial registration: ClinicalTrials.

3. ir.apollomicsinc.com ir.apollomicsinc.com/news-releases/news-release-details/apollomics-presents-vebreltinib-data-patients-non-small-cell

Apollomics Presents Vebreltinib Data in Patients with Non- ... “We are pleased to share the efficacy and safety data of vebreltinib showing it is efficacious in both treatment naïve and previously treated ...

4. jto.org jto.org/article/S1556-0864(25)01967-7/fulltext

P3.12.55 Efficacy of Vebreltinib in Advanced NSCLC ... Vebreltinib (PLB1001), a potent and highly selective c-MET inhibitor, demonstrated superior objective response rate (ORR) benefits in locally advanced or ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02956-9/fulltext

1382P Vebreltinib efficacy and safety in NSCLC patients ... Vebreltinib is efficacious in NSCLC patients with centrally confirmed METex14 skipping, with an acceptable safety profile.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07156604

Vebreltinib for Neoadjuvant in METex 14 Skipping Mutant ... This is a prospective, single-center phase II clinical study aimed at evaluating the efficacy and safety of Vebreltinib in neoadjuvant treatment for ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1556086423014168

P2.09-41 Phase I/II Study Exploring Safety and Efficacy of ... P2.09-41 Phase I/II Study Exploring Safety and Efficacy of Apl-101 Plus Frontline Osimertinib in EGFR-mutated Metastatic Non-small Cell Lung Cancer.