ABSK-021 for Cancer

Recruiting at 8 trial locations

Overseen By YUAN LU

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Abbisko Therapeutics Co, Ltd

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

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

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

276 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new oral treatment called ABSK021 (also known as Pimicotinib) for individuals with advanced solid tumors, which are cancers that have spread and don't respond to standard treatments. The main goal is to determine if ABSK021 is safe and to identify the best dose for future studies. Researchers will also assess whether it shows any early signs of fighting cancer. Individuals with a confirmed solid tumor who have tried other treatments without success, or have no other options, might be suitable candidates for this trial. 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 requires that you stop any previous anti-cancer therapy, including chemotherapy, radiotherapy, endocrine therapy, or molecular targeted therapy, at least 4 weeks before starting the study treatment. Additionally, you cannot use strong inhibitors or inducers of CYP3A4 while participating in the trial.

Is there any evidence suggesting that ABSK021 is likely to be safe for humans?

Research has shown that ABSK021, also known as pimicotinib, is generally safe based on previous studies. Tested in doses of 50 mg and 25 mg taken once daily, it was well-tolerated, with no signs of liver damage. Other studies reported similar safety results, with few serious or unexpected side effects. This suggests that ABSK021 is relatively safe for people, based on data from various clinical settings. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard cancer treatments that often focus on chemotherapy or radiation, ABSK021 is unique because it targets a specific pathway involved in cancer cell growth. This oral medication is designed to home in on a distinct mechanism that may reduce the side effects typically associated with traditional cancer therapies. Researchers are excited about ABSK021 because it offers the potential for more precise treatment by escalating doses based on individual safety data, which might lead to better outcomes and improved quality of life for patients.

What evidence suggests that ABSK021 might be an effective treatment for cancer?

Research has shown that ABSK021, also known as pimicotinib, may help treat certain tumors by blocking a protein called CSF-1, which some tumors need to grow. Studies have found that it can significantly shrink tumors and improve symptoms for people with tenosynovial giant cell tumor (TGCT). Patients reported better physical function and less pain. The treatment was also found to be safe, with no major liver-related side effects. Overall, the evidence suggests that ABSK021 could be an effective option for treating certain types of tumors. ^{4 6 7 8 9}

Who Is on the Research Team?

Siqing FU, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors, including Giant Cell Tumor of the tendon sheath or pigmented villonodular synovitis, who have tried other treatments without success or can't undergo surgery. Participants must be able to swallow pills, not have had recent cancer treatment or major surgery, and should not be pregnant or nursing.

Inclusion Criteria

ECOG (electrocorticogram) performance status 0~1

Life expectancy ≥ 3 months

Your organs and bone marrow are working properly.

Exclusion Criteria

Inability to take oral medication or significant nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption of oral medication

Previous anti-cancer therapy, including chemotherapy, radiotherapy, endocrine therapy or molecular targeted therapy within ≤ 5-halflife or ≤ 4 weeks (whichever is shorter) prior to initiation of study treatment (chemotherapy with nitrosourea or mitomycin should be 6 weeks prior to initiation of study treatment)

Major surgery within 4 weeks of the first dose of study drug and all surgical wounds must be healed and free of infection or dehiscence

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 ABSK021 with a starting dose of 25mg once daily, guided by '3+3' escalation rules based on safety data until an MTD or RDE is identified.

28-day cycles

Multiple visits for dose administration and monitoring

Expansion

Expansion part of oral ABSK021 at recommended dose of expansion (RDE) for further evaluating safety and tolerability among selected tumor types.

28-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• ABSK021

Trial Overview The study tests ABSK-021, an oral medication for advanced solid tumors. It's an early-phase trial to find out how safe it is and what dose works best. Researchers will also look at any signs that the drug might shrink the tumors.

How Is the Trial Designed?

Group I: ABSK021 Experimental Treatment 1 Intervention

Dose escalation of oral ABSK021 with a starting dose of 25mg once daily will be guided by"3+3" escalation rules based on safety data until an MTD has been identified or a RDE. For each dose, patients will first receive a single dose ABSK021 tablet(s) by mouth at Day -3 and be followed by a 3-day off as a run-in period to access the safety and PK of single-dose. Then, patients will continuously receive ABSK021 once daily (QD) in repeated 28-day cycles.

ABSK021 is already approved in China, United States for the following indications:

Approved in China as Pimicotinib for:

• Tenosynovial Giant Cell Tumor (TGCT)

Approved in United States as Pimicotinib for:

• Tenosynovial Giant Cell Tumor (TGCT)

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 phase I trial involving 120 patients with solid tumors, apitolisib (GDC-0980) was found to be reasonably tolerated at a dose of 30 mg, with the recommended phase 2 dose (RP2D) established at 40 mg once daily, despite some severe side effects like hyperglycemia and pneumonitis.

The treatment showed promising preliminary antitumor activity, with 10 confirmed partial responses in various cancer types, and significant modulation of target pathways was observed, indicating its potential effectiveness as a cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of Apitolisib (GDC-0980), Dual Phosphatidylinositol-3-Kinase and Mammalian Target of Rapamycin Kinase Inhibitor, in Patients with Advanced Solid Tumors. Dolly, SO., Wagner, AJ., Bendell, JC., et al.[2022]

STX-478 is a novel allosteric inhibitor that selectively targets mutant forms of the PI3Kα enzyme, showing strong efficacy in preclinical models without the severe side effects like hyperglycemia associated with the nonselective inhibitor alpelisib.

Combining STX-478 with other treatments, such as fulvestrant and CDK4/6 inhibitors, resulted in significant and durable tumor regression in estrogen receptor-positive, HER2-negative cancer models, indicating its potential for improved therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts. Buckbinder, L., St Jean, DJ., Tieu, T., et al.[2023]

In the BASALT-1 study, only 23.3% of squamous and 20.0% of nonsquamous NSCLC patients treated with the PI3K inhibitor buparlisib showed progression-free survival at 12 weeks, indicating limited efficacy as a monotherapy.

The study found that while PI3K pathway activation can be detected in circulating tumor DNA (ctDNA), it may not be the primary driver of tumor growth in NSCLC, suggesting that combining PI3K inhibitors with other treatments could be more effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Buparlisib (BKM120) in Patients with PI3K Pathway-Activated Non-Small Cell Lung Cancer: Results from the Phase II BASALT-1 Study. Vansteenkiste, JF., Canon, JL., De Braud, F., et al.[2022]

Advanced prostate cancers that are resistant to castration treatments are life-threatening and currently lack curative options, highlighting the urgent need for new therapies.

Recent studies indicate that the PI-3 kinase p110β is overexpressed in advanced prostate cancers and plays a crucial role in their development, leading to the development of specific inhibitors that are now being tested in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PI-3 kinase p110β: a therapeutic target in advanced prostate cancers. Li, B., Sun, A., Jiang, W., et al.[2020]

In a study involving 35 patients with PIK3CA mutations, copanlisib demonstrated a 16% objective response rate, indicating its potential effectiveness in treating certain tumors that are resistant to other therapies.

The treatment was associated with manageable side effects, including hyperglycemia and fatigue, with 53% of patients experiencing grade 3 toxicities, suggesting that while copanlisib is active, careful monitoring for adverse effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Copanlisib in Patients With Tumors With PIK3CA Mutations: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1F. Damodaran, S., Zhao, F., Deming, DA., et al.[2023]

In a study of 1200 cancer patients, 11.8% had PIK3CA and/or PIK3R1 mutations, with a significant portion (78.4%) being activating mutations, indicating a potential role in various cancer types beyond just ER+/HER2- metastatic breast cancer.

The efficacy of first-line chemotherapy in ER+/HER2- metastatic breast cancer was similar for tumors with PIK3CA mutations compared to those without, while in triple-negative metastatic breast cancer, chemotherapy was more effective in tumors without PIK3CA mutations, suggesting the need for further evaluation of PI3K inhibitors in broader contexts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PIK3CA and PIK3R1 tumor mutational landscape in a pan-cancer patient cohort and its association with pathway activation and treatment efficacy. Tharin, Z., Richard, C., Derangère, V., et al.[2023]

In a study of 1,125 lung adenocarcinoma patients, 2% were found to have PIK3CA mutations, which often occurred alongside other mutations like EGFR and KRAS, indicating a complex genetic landscape in these tumors.

The presence of PIK3CA mutations in lung adenocarcinomas raises questions about their impact on the effectiveness of targeted therapies, suggesting that comprehensive genetic testing should be performed for better treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Coexistence of PIK3CA and other oncogene mutations in lung adenocarcinoma-rationale for comprehensive mutation profiling. Chaft, JE., Arcila, ME., Paik, PK., et al.[2023]

Next-generation allosteric mutant and isoform-selective PIK3CA inhibitors show promise in targeting solid tumors with PIK3CA mutations, potentially offering improved efficacy and safety compared to traditional PI3K inhibitors that affect both mutant and wild-type forms.

Preclinical studies indicate that these selective inhibitors can effectively inhibit mutant PIK3CA without causing significant metabolic side effects, which are common with conventional PI3K inhibitors, although their effectiveness may vary for patients with multiple or rare mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The emerging role of PI3K inhibitors for solid tumour treatment and beyond. Belli, C., Repetto, M., Anand, S., et al.[2023]

In a phase Ib study involving 146 patients with advanced solid tumors, the combination of pimasertib (a MEK1/2 inhibitor) and voxtalisib (a pan-PI3K and mTORC1/mTORC2 inhibitor) was found to have a maximum-tolerated dose of 90 mg and 70 mg respectively, with a recommended phase 2 dose of 60 mg for pimasertib.

Despite some initial responses, including one complete response and five partial responses, the treatment showed poor long-term tolerability, with 73% of patients requiring dose interruptions and 26% discontinuing due to treatment-emergent adverse events like diarrhea and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase Ib dose-escalation and expansion study of the oral MEK inhibitor pimasertib and PI3K/MTOR inhibitor voxtalisib in patients with advanced solid tumours. Schram, AM., Gandhi, L., Mita, MM., et al.[2021]

In a phase Ib study involving patients with hormone therapy-refractory ER+ metastatic breast cancer, combining the PI3K inhibitor buparlisib with letrozole showed clinical benefits, particularly in patients with PIK3CA and MAP3K1 mutations.

Patients with both PIK3CA and MAP3K1 mutations had the highest likelihood of clinical benefit, suggesting that luminal A subtype tumors may be a key target population for this combination therapy, although the exact role of MAP3K1 mutations in response to treatment remains unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PIK3CA and MAP3K1 alterations imply luminal A status and are associated with clinical benefit from pan-PI3K inhibitor buparlisib and letrozole in ER+ metastatic breast cancer. Nixon, MJ., Formisano, L., Mayer, IA., et al.[2023]

Citations

1. emdserono.com emdserono.com/us-en/company/news/press-releases/pimicotinib-maneuver-longer-term-results-esmo-2025-17-10-2025

2025-10-17 Pimicotinib MANEUVER Longer Term Results ... Pimicotinib Treatment Demonstrates Deep and Durable Tumor Responses and Continued Improvements in Pain and Function for Patients with TGCT. The ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.11500

Pimicotinib in tenosynovial giant cell tumor (TGCT) Pimi produced statistically significant and clinically meaningful improvements in physical function and symptoms, representing an effective, well-tolerated and ...

3. merckgroup.com merckgroup.com/en/news/pimicotinib-topline-results-12-11-2024.html

Pimicotinib Significantly Improved Outcomes for Patients ... Phase III MANEUVER trial of pimicotinib met its primary endpoint, demonstrating significant improvement in objective response rate in TGCT-patients.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39287124/

MANEUVER: A Phase III study of pimicotinib to assess ... Pimicotinib is a medicine which blocks CSF-1, and researches have shown that it is safe and effective for treating TGCT in smaller, early study.

5. asco.org asco.org/abstracts-presentations/ABSTRACT407670

Efficacy and safety profile of pimicotinib (ABSK021) in ... Pimicotinib has demonstrated a significant antitumor activity, favorable safety, and PK profiles at both 50 mg QD and 25 mg QD with no apparent hepatotoxicity.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.11559

Efficacy and safety profile of pimicotinib (ABSK021) in ... Pimicotinib has demonstrated a significant antitumor activity, favorable safety, and PK profiles at both 50 mg QD and 25 mg QD with no apparent hepatotoxicity.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05804045

Study of Pimicotinib (ABSK021) for Tenosynovial Giant Cell ... The goal of this clinical trial is to assess the efficacy and safety of Pimicotinib (ABSK021) in patients with Tenosynovial Giant Cell Tumor (TGCT).

8. emdserono.com emdserono.com/us-en/company/news/press-releases/pimicotinib-topline-results-12-11-2024.html

Pimicotinib Significantly Improved Outcomes for Patients ... In MANEUVER, pimicotinib was well-tolerated, and the safety profile was consistent with previously reported data, with no evidence of ...

9. targetedonc.com targetedonc.com/view/pimicotinib-shows-promising-efficacy-and-tolerability-in-tgct

Pimicotinib Shows Promising Efficacy and Tolerability in ... Pimicotinib (ABSK021) led to an objective response rate (ORR) at week 25 of 54.0% in patients with tenosynovial giant cell tumor (TGCT) vs ...