ABSK061 for Solid Tumors

Recruiting at 21 trial locations

Overseen By Yuan LU

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Abbisko Therapeutics Co, Ltd

Must not be taking: FGFR inhibitors

Disqualifiers: Active CNS metastases, Cardiac disease, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

85 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ABSK061 for individuals with advanced solid tumors. It aims to determine the safest dose and evaluate its effectiveness against specific cancer types. The trial seeks participants whose cancer has not responded to standard treatments, particularly those with urothelial carcinoma or cholangiocarcinoma with specific genetic changes (FGFR2/3). For those with these cancers who have not benefited from standard treatments, this trial may be suitable. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take certain drugs that might interact with the study drug, and you must avoid certain foods like grapefruit and pomegranates. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that ABSK061 is likely to be safe for humans?

Research has shown that ABSK061 is generally safe for patients. Studies involving individuals with advanced solid tumors found that most did not experience serious side effects from ABSK061, and some even responded well to the treatment. Although the treatment remains under investigation, these results suggest that ABSK061 is safe for current human trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about ABSK061 because it offers a novel approach to tackling solid tumors by targeting pathways that current treatments might not effectively address. Unlike standard chemotherapy or targeted therapies, ABSK061 is an oral medication, which could make it more convenient for patients. The treatment's potential to be fine-tuned through dose escalation and its promising mechanism of action make it a standout candidate in the ongoing quest for more effective cancer therapies.

What evidence suggests that ABSK061 might be an effective treatment for solid tumors?

Research has shown that ABSK061, the investigational treatment in this trial, may help treat solid tumors, particularly those with specific genetic changes called FGFR2 or FGFR3 alterations. In earlier studies, ABSK061 reduced tumor size in 37.5% of patients with these genetic changes. The treatment was well tolerated, with patients experiencing manageable side effects. These early results suggest that ABSK061 could be an effective option for treating certain advanced solid tumors. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors, specifically urothelial carcinoma or cholangiocarcinoma that's worsened despite treatment or when no standard treatment exists. Participants must have measurable lesions, a life expectancy of at least 3 months, and certain genetic alterations in their tumors. They need good organ function and can't be part of the trial if they've had recent major surgery, untreated brain metastases, active hepatitis or HIV infections, heart problems, eye diseases affecting the retina or cornea, uncontrolled fluid accumulation in the body cavities, are pregnant/nursing or unwilling to use effective contraception.

Inclusion Criteria

Patient should understand, sign, and date the written informed consent form prior to screening

My blood tests meet the required levels for the study.

Life expectancy ≥3 months

Exclusion Criteria

Any other clinically significant comorbidities, such as uncontrolled pulmonary disease, active infection, or any other condition, which in the judgment of the Investigator, could compromise compliance with the protocol, interfere with the interpretation of study results, or predispose the patient to safety risks

I cannot take pills due to severe nausea, vomiting, or issues with my digestive system.

I have another cancer that is getting worse or needs treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Dose escalation of oral ABSK061 guided by the Bayesian optimal interval (BOIN) design to identify maximum tolerated dose (MTD) or maximum administered dose (MAD).

28 days per cycle

Multiple visits per cycle

Expansion

Investigation of oral ABSK061 at the recommended dose for expansion (RDE) to further evaluate safety and tolerability among selected tumor types.

28 days per cycle

Multiple visits per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ABSK061

Trial Overview The study tests ABSK061 given orally over repeated 28-day cycles to see how safe it is and how well patients tolerate it. It starts with dose escalation to find an appropriate dose level followed by expansion at this recommended dose among selected tumor types while also checking preliminary effects on tumor size.

How Is the Trial Designed?

Group I: ABSK061 Experimental Treatment 1 Intervention

Dose escalation of oral ABSK061 will be guided by the Bayesian optimal interval (BOIN) design based on safety data collected until a maximum tolerated dose (MTD) or maximum administered dose (MAD) has been identified. During the dose escalation part of the study, patients will receive a single dose of ABSK061 on C1D1 only, and then BID dosing for the rest of the days of cycle 1 and in the subsequent cycles. If the actual elimination half-life of ABSK061 is greatly exceeding that predicted, a run-in period with a single-dose and a longer drug-free observation period could be performed in subsequent patients after the Investigator and Sponsor have discussed and agreed.

Who Is Running the Clinical Trial?

Abbisko Therapeutics Co, Ltd

Lead Sponsor

Trials

26

Recruited

1,700+

Published Research Related to This Trial

In a study of 452 premenopausal early-stage breast cancer patients, overexpression of the P70 S6 kinase protein (PS6K) was linked to worse outcomes, including lower distant disease-free survival and impaired locoregional control.

PS6K overexpression was identified as an independent predictor of poor locoregional control, suggesting it could be a valuable marker for guiding treatment strategies in early-stage breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overexpression of P70 S6 kinase protein is associated with increased risk of locoregional recurrence in node-negative premenopausal early breast cancer patients. van der Hage, JA., van den Broek, LJ., Legrand, C., et al.[2022]

The gene MPS1 is significantly correlated with TP53 mutation status and serves as a strong prognostic marker in estrogen receptor-positive breast cancer, remaining effective regardless of treatment type.

Inhibition of MPS1 using the small molecule SP600125 reduces cell viability and increases cell death in TP53-mutated breast cancer cells, and enhances the effectiveness of chemotherapy, suggesting MPS1 as a promising therapeutic target.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TP53 mutation-correlated genes predict the risk of tumor relapse and identify MPS1 as a potential therapeutic kinase in TP53-mutated breast cancers. Győrffy, B., Bottai, G., Lehmann-Che, J., et al.[2022]

LKB1-signaling is associated with improved survival rates in overall breast cancer, indicating its potential as a therapeutic target.

The relationship between LKB1-signaling and patient survival varies by breast cancer subtype, with NUAK2 showing improved survival in ER-negative tumors but worse outcomes in ER-positive tumors, highlighting the complexity of targeting this pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of liver kinase B1 downstream signaling expression in various breast cancers and relapse free survival after systemic chemotherapy treatment. Nguyen, K., Rivera, A., Alzoubi, M., et al.[2021]

In a study of 304 breast cancer tissues, the presence of phosphorylated S6 kinase 1 (p-S6K1) was identified as a significant independent prognostic factor for worse overall and breast cancer-specific survival in patients with hormone receptor-positive (HR (+)) tumors, indicating a potential link to endocrine therapy resistance.

Among the HR (+) group, 35.5% of patients were positive for p-S6K1, and its expression correlated with a higher risk of poor outcomes (hazard ratios of 2.62 and 3.25 for overall and breast cancer-specific survival, respectively), while no such association was found in hormone receptor-negative (HR (-)) tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phosphorylated S6K1 is a possible marker for endocrine therapy resistance in hormone receptor-positive breast cancer. Kim, EK., Kim, HA., Koh, JS., et al.[2015]

Overexpression of the homeoprotein Six1 significantly promotes tumor growth and metastasis in colorectal cancer (CRC), as demonstrated in mouse models using MC38 colon adenocarcinoma cells.

Six1 enhances cancer stem cell features and stimulates angiogenesis by increasing vascular endothelial growth factor (VEGF) levels, while also activating MAPK signaling, suggesting potential targets for pharmacological intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Six1 promotes colorectal cancer growth and metastasis by stimulating angiogenesis and recruiting tumor-associated macrophages. Xu, H., Zhang, Y., Peña, MM., et al.[2018]

The Six1cTerm antibody specifically detects the Six1 protein, which is present in up to 54% of ovarian cancer tissue samples, indicating its potential role in tumor biology.

High levels of Six1 protein in metastatic ovarian cancer are associated with poorer survival outcomes, suggesting that Six1 could serve as a prognostic marker for patients with high-grade serous ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Specificity and prognostic validation of a polyclonal antibody to detect Six1 homeoprotein in ovarian cancer. Qamar, L., Deitsch, E., Patrick, AN., et al.[2021]

Knockdown of p70S6K in the highly metastatic MDA-231 breast cancer cell line significantly inhibited cell growth, migration, and invasion, suggesting that targeting p70S6K could be a potential therapeutic strategy.

In an animal model, mice with p70S6K knockdown developed significantly smaller tumors and showed no metastasis, while control mice exhibited lung metastasis, highlighting the critical role of p70S6K in breast cancer progression and metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting p70S6K prevented lung metastasis in a breast cancer xenograft model. Akar, U., Ozpolat, B., Mehta, K., et al.[2023]

The Six1 protein is linked to the progression of colorectal cancer, and its overexpression is associated with worse survival rates in advanced cases, making it a potential target for therapy.

Using a lentivirus to knock down Six1 expression in colorectal cancer cells significantly reduced cell growth, migration, and invasion in lab tests, and also inhibited tumor growth in animal models, suggesting a promising new treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting Six1 by lentivirus-mediated RNA interference inhibits colorectal cancer cell growth and invasion. Li, Z., Tian, T., Hu, X., et al.[2021]

Citations

1. esmoopen.com esmoopen.com/article/S2059-7029(24)00042-5/fulltext

45O First-in-human study of ABSK061 This study demonstrated the anti-tumor activity of ABSK061 in patients with FGFR2/3 alterations and its favorable safety profile, which warrants further ...

2. onclive.com onclive.com/view/absk061-demonstrates-safety-preliminary-efficacy-in-fgfr2-3-advanced-solid-tumors

ABSK061 Demonstrates Safety, Preliminary Efficacy in ... ABSK061 was well tolerated and elicited responses in patients with advanced solid tumors harboring FGFR2/3 alterations.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05244551

NCT05244551 | A Study to Assess Safety, Tolerability, and ... A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK061 in Patients With Advanced Solid Tumors · Study Overview · Contacts and Locations.

4. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/545555

A Phase 2 Clinical Study of ABSK061 and ABSK043 The purpose of this study is to evaluate the anti-tumor activity of ABSK061 + ABSK043 in terms of overall response rate (ORR) in in Patients ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0165614725002202

Next-generation isoform-selective fibroblast growth factor ... Among patients with solid tumors harboring FGFR2 alterations or FGFR3 fusions, the objective response rate was 37.5%. Compared with pan-FGFR ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05244551

NCT05244551 | A Study to Assess Safety, Tolerability, and ... A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK061 in Patients With Advanced Solid Tumors · Study Overview · Contacts and Locations.

7. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/46/NCT07007546/Prot_000.pdf

A study to evaluate the safety, tolerability, and Based on the data from the Phase 1 trial in patients with solid tumors of ABSK061-101, the weighted mean of the geometric coefficient of variation. (CVw%) of ...

8. clinicaltrial.be clinicaltrial.be/fr/details/453878?per_page=100&only_recruiting=0&only_eligible=0&only_active=0

A Phase 2 Clinical Study of ABSK061 and ABSK043 ABSK061 is a selective and potent pan FGFR 2/3 inhibitor with demonstrated clinical activity in participants with a variety of FGFR ...