ABN401 for Solid Tumors

Recruiting at 44 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 tests a new treatment called ABN401 (vabametkib) for individuals with advanced solid tumors that have specific changes in the c-MET gene. The trial aims to evaluate the treatment's effectiveness, safety, and how the body processes it. Participants are divided into two groups: one will take ABN401 alone, while the other will take it with another drug called Lazertinib. Individuals with advanced, recurring, or metastatic non-small cell lung cancer (NSCLC) and specific genetic changes or treatment history may be suitable for this study. 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 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.

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

A previous study showed that vabametkib effectively fought tumors and was well-tolerated by patients with a specific type of lung cancer, with fewer side effects than some approved treatments. Another study confirmed vabametkib's safety in earlier trials.

When combined with lazertinib, which targets cancer cells differently, vabametkib remained safe. Researchers are studying this combination to better understand how these two treatments work together.

Overall, earlier research suggests that vabametkib, whether used alone or with lazertinib, appears safe and well-tolerated by patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ABN401, particularly the combination of vabametkib and lazertinib, because it targets solid tumors with a potentially novel mechanism. Vabametkib is thought to work differently from traditional chemotherapy or immunotherapy by specifically inhibiting certain pathways that help cancer cells grow. The combination with lazertinib, an existing EGFR inhibitor, aims to enhance this effect, potentially offering a more effective treatment option. This approach could provide a more targeted and efficient attack on cancer cells compared to standard treatments, which often involve broad approaches like chemotherapy or radiation.

What evidence suggests that this trial's treatments could be effective for solid tumors?

Research has shown that ABN401, also known as vabametkib, may help treat advanced solid tumors with specific c-MET changes. Studies have found that ABN401 can significantly slow tumor growth, especially in cases with genetic changes like MET exon 14 skipping. It also has a good safety record, causing fewer side effects than some current treatments. In this trial, participants in Cohort 1 will receive ABN401 alone, while those in Cohort 2 will receive ABN401 with lazertinib. When combined with lazertinib, ABN401 has shown strong effects against tumors, particularly in non-small cell lung cancer. Overall, both ABN401 alone and with lazertinib have proven effective in early studies, offering hope for people with certain types of cancer. ^{1 2 6 7 8}

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 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]

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]

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. clinicaltrials.gov clinicaltrials.gov/study/NCT05541822

Study Details | NCT05541822 | To Evaluate the Efficacy, ... To Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetic Profile of ABN401 in Patients With Advanced Solid Tumors Harboring c-MET Dysregulation.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.8640

Vabametkib in MET exon 14 skipping non-small-cell lung ... Vabametkib demonstrates good antitumor activity in pts with METex14 NSCLC, and better toxicity profile with excellent tolerability, compared to FDA-approved ...

3. delta.larvol.com delta.larvol.com/Products/?ProductId=12e1ef56-b601-4ba1-b987-c8804c2655b8

vabametkib (ABN401) / Abion Vabametkib demonstrates good antitumor activity in pts with METex14 NSCLC, and better toxicity profile with excellent tolerability, compared to FDA-approved ...

4. withpower.com withpower.com/trial/phase-2-solid-tumors-advanced-solid-tumors-11-2022-642d9

ABN401 for Solid Tumors This Phase 2 medical study run by Abion Inc is evaluating whether ABN401 will have tolerable side effects & efficacy for patients with Solid Tumors.

5. researchgate.net researchgate.net/publication/392071621_Phase_2_cohort-2_trial_in_progress_Vabametkib_plus_lazertinib_for_patients_with_EGFR-mutant_NSCLC_who_developed_resistance_to_1st-line_3rd-gen-EGFR_TKIs_via_C-Met_dysregulation

Vabametkib plus lazertinib for patients with EGFR-mutant ... We identified the most relevant patient-reported symptomatic adverse events (AEs) to measure in patients with non-small cell lung cancer (NSCLC) ...

6. abionbio.com abionbio.com/2023/11/27/abion-presents-new-efficacy-data-for-abn401-a-novel-met-tki-for-advanced-non-small-cell-lung-cancer/

ABION Presents New Efficacy Data for ABN401, a Novel ... The cut-off data reaffirm ABN401's excellent safety profile as shown in an earlier Phase 1 trial. A total of 24 patients received ABN401 800 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7352216/

Therapeutic Efficacy of ABN401, a Highly Potent and ... The low off-target activity of ABN401 suggests the safety of the kinase inhibitor. ... solid tumors (NCT04052971). In particular, the clinical trial included ...

8. medchemexpress.com medchemexpress.com/abn401.html?srsltid=AfmBOooxGWz4BZp_n3ZVkmOQHvls4XYs1pn3UF4ZJisrqMdrj9CVDI7Q

ABN401 | c-MET Inhibitor ABN401 is cytotoxic to MET-addicted cancer cells with the IC50 of 2-43 nM. ABN401 has bioavailability in rats and dogs of 42.1-56.2% and 27.4-37.7%, ...