ABN401 for Solid Tumors

Recruiting at 27 trial locations

Overseen By Viki Kim

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Abion Inc

Must not be taking: Corticosteroids, PPI, CYP3A4 inhibitors

Disqualifiers: Liver disease, Lung disease, CNS tumor, 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: Unknown

Duration: Up to 12 months

178 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing ABN401, a new drug, in patients with advanced cancers that have a specific genetic change. The drug works by blocking a protein that helps cancer cells grow, aiming to stop or slow down the cancer.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as strong and moderate inhibitors/inducers of P-glycoprotein and CYP3A4, proton pump inhibitors, and systemic corticosteroids over 10 mg/day prednisone or equivalent, at least 1 week before starting the study. If you are on these medications and cannot stop them, you may not be eligible to participate.

What data supports the effectiveness of the drug ABN401 for solid tumors?

The research shows that drugs similar to ABN401, like crizotinib, have been effective in treating certain types of lung cancer with specific genetic changes. Additionally, MEK inhibitors, which are similar to one of the components in the treatment, have shown significant responses in certain types of melanoma, suggesting potential effectiveness in targeting specific cancer pathways. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

Adults with advanced solid tumors showing c-MET dysregulation, who have an ECOG performance status of 0 or 1 and a life expectancy of at least 3 months. They must have adequate organ function, agree to use effective birth control, and can't be on certain medications that affect ABN401 absorption or processing. Patients should not have had more than two prior cancer treatments and must not be pregnant or breastfeeding.

Inclusion Criteria

Have a life expectancy of at least 3 months

If not menopausal or surgically sterile, willing to practice at least one of the following highly effective methods of birth control

ALL subjects must undergo blood sample for biomarker assessment

Exclusion Criteria

Patients with a corrected QT interval (QTcF) of > 470 msec (females) and > 450 msec (males)

I am currently being treated for an infection.

Pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ABN401 800 mg, monotherapy, administered orally once daily in 21-day cycles

Up to 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ABN401

Trial Overview The trial is testing the drug ABN401's effectiveness, safety, tolerability, and how it's processed in the body when given alone to patients with specific types of advanced solid tumors that have changes in a gene called c-MET.

How Is the Trial Designed?

Group I: Cohort 2: Lazertinib & Vabametkib Experimental Treatment 2 Interventions

Part 1 (Safety Run-in): Subjects will receive lazertinib 240 mg in combination with one of three assigned dose levels of vabametkib, administered orally once daily in 21-day cycles Part 2 (Random Dose Optimization): A maximum of two vabametkib dose levels will be evaluated in this part. Patients will be randomized in 1:1 ratio to vabametkib dose level 1 (selected from Part 1) plus the determined dose of lazertinib or dose level 2 (selected from Part 1) plus the determined dose of lazertinib Part 3 (Randomized Clinical Trial): Patients will be randomized in 1:1 ratio to optimized vabametkib dose (selected from Part 2) plus lazertinib or Standard of Care (SOC) arm. SOC arm will be decided by the time of Part 3 initiation

Group II: Cohort 1: Vabametkib Experimental Treatment 1 Intervention

Subjects will receive vabametkib 800 mg, monotherapy, administered orally once daily in 21-day cycles

Who Is Running the Clinical Trial?

Abion Inc

Lead Sponsor

Trials

3

Recruited

90+

Published Research Related to This Trial

In a study of 106 patients with ALK-positive non-small cell lung cancer, 6.5% exhibited primary resistance to crizotinib, resulting in a median progression-free survival of only 1.2 months, compared to 47.0 months for long-term responders.

Patients who received next-generation ALK inhibitors after crizotinib progression had significantly better survival outcomes than those who only received supportive care, highlighting the potential for improved treatment strategies in this resistant population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical features and outcomes of ALK rearranged non-small cell lung cancer with primary resistance to crizotinib. Ma, D., Zhang, Y., Xing, P., et al.[2020]

In a study of 856 patients with advanced BRAFV600-mutant melanoma, 275 (32%) had brain metastases, and those treated with the BRAF and MEK inhibitors dabrafenib and trametinib had a median progression-free survival (PFS) of 5.68 months.

Factors such as an ECOG performance status of 1 or higher, elevated serum lactate dehydrogenase (LDH), and having three or more metastatic sites were linked to shorter PFS, highlighting the need for tailored treatment strategies for patients with brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open label, non-randomised, phase IIIb study of trametinib in combination with dabrafenib in patients with unresectable (stage III) or distant metastatic (stage IV) BRAF V600-mutant melanoma: A subgroup analysis of patients with brain metastases. Dutriaux, C., Robert, C., Grob, JJ., et al.[2022]

Crizotinib has demonstrated effectiveness in treating non-small cell lung cancer (NSCLC) specifically in patients with alterations in the MET exon 14, indicating its targeted therapeutic potential.

This finding highlights the importance of genetic testing in NSCLC to identify patients who may benefit from crizotinib treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multikinase Inhibitor Crizotinib Is Active in MET Exon 14-Altered Lung Cancer. [2020]

In a study comparing brigatinib, ceritinib, and alectinib for treating crizotinib-refractory ALK+ non-small cell lung cancer, brigatinib showed significantly longer progression-free survival (PFS) and overall survival (OS) compared to ceritinib, with PFS medians of 15.7 months for ceritinib versus 18.3 months for brigatinib.

Brigatinib also demonstrated longer PFS compared to alectinib, with medians of 17.6 months for brigatinib versus 8.2 months for alectinib, although the OS results between these two were inconclusive.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy of brigatinib versus ceritinib and alectinib in patients with crizotinib-refractory anaplastic lymphoma kinase-positive non-small cell lung cancer. Reckamp, K., Lin, HM., Huang, J., et al.[2020]

A patient with metastatic melanoma harboring a GOLGA4-RAF1 fusion and mutations in CTNNB1 and CDKN2A showed a significant clinical response to MEK inhibitor therapy after failing anti-CTLA4/anti-PD1 immunotherapy.

The study highlights the importance of molecular characterization in treatment-resistant cancers, as it can reveal actionable targets that lead to personalized and effective treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profound MEK inhibitor response in a cutaneous melanoma harboring a GOLGA4-RAF1 fusion. McEvoy, CR., Xu, H., Smith, K., et al.[2023]

Citations

1. Singapore pubmed.ncbi.nlm.nih.gov

Clinical features and outcomes of ALK rearranged non-small cell lung cancer with primary resistance to crizotinib. [2020]

2. England pubmed.ncbi.nlm.nih.gov

An open label, non-randomised, phase IIIb study of trametinib in combination with dabrafenib in patients with unresectable (stage III) or distant metastatic (stage IV) BRAF V600-mutant melanoma: A subgroup analysis of patients with brain metastases. [2022]

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

Multikinase Inhibitor Crizotinib Is Active in MET Exon 14-Altered Lung Cancer. [2020]

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

Comparative efficacy of brigatinib versus ceritinib and alectinib in patients with crizotinib-refractory anaplastic lymphoma kinase-positive non-small cell lung cancer. [2020]

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

Profound MEK inhibitor response in a cutaneous melanoma harboring a GOLGA4-RAF1 fusion. [2023]