Evaluating ABSK061 and ABSK043 for treating advanced solid tumors

An Open-label Phase 2, Multicenter, Open-Label Clinical Study to Evaluate the Safety and Efficacy of ABSK061 and ABSK043 with or Without Chemotherapy in Patients with Metastatic/Unresectable Solid Tumors with FGFR2/3 Alterations

This study is testing a new combination of two drugs to see if they can help people with advanced solid tumors that have specific genetic changes.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 202 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Abbisko Therapeutics Co, Ltd (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 21 sites (Guiyang, Guizhou and 20 other locations)
• Trial ID: NCT06632262 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to assess the anti-tumor activity of the combination of ABSK061, a selective FGFR 2/3 inhibitor, and ABSK043, a PD-L1 inhibitor, in patients with metastatic or unresectable solid tumors that have FGFR2/3 alterations. The study includes a screening phase, a treatment phase, and a post-treatment follow-up phase. Participants will receive either the drug combination alone or in combination with CAPOX, depending on their cohort. The overall response rate (ORR) will be the primary endpoint evaluated throughout the trial.

Who should consider this trial

Good fit: Ideal candidates include patients with metastatic or unresectable solid tumors that have FGFR2/3 alterations and have progressed after standard therapies.

Not a fit: Patients without FGFR2/3 alterations or those with tumors that are not metastatic or unresectable may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with specific genetic alterations in their tumors.

How similar studies have performed: Other studies have shown promise with FGFR and PD-L1 inhibitors, suggesting potential for success with this combination approach.

Eligibility criteria

Inclusion Criteria:

* Patients must have a measurable target lesion (per RECIST v1.1) (not applicable to expansion cohort 1) where:
* Dose Escalation: patients with histologically confirmed solid tumors who have progressed after standard of care, are unable to tolerate standard therapy, or have no standard of care currently available:
* Patients must have the a central laboratory or previous test report confirming FGFR2/3 gene activatingon alterations (including FGFR2/3 activating mutations, fusions/rearrangements, or FGFR2 amplifications) or overexpression in tumor tissue or blood based on central laboratory test or previous test reports.
* Expansion Phase:
* Cohort 1 (HER2-gastric/gastroesophageal junction cancer)
* Histologically or cytologically confirmed metastatic/unresectable gastric/gastroesophageal junction cancer, HER2 test negative
* The patient had FGFR2 amplification or overexpression in tumor tissue confirmed by a central laboratory test or a previous test report (previous test report only applied to FGFR2 amplification)
* Patients need to provide prior tumor tissue or willingness to undergo biopsy if no prior tumor tissue or insufficient quantity is required
* No prior (or up to one course of chemotherapy) systemic therapy for advanced gastric/gastroesophageal junction cancer, or disease progression more than 6 months after the end of the last prior adjuvant therapy
* Patients must have a measurable target lesion or evaluable non-target lesion (per RECIST v1.1)
* Cohort 2 (urothelial carcinoma)
* Histologically or cytologically confirmed metastatic/unresectable urothelial carcinoma with other histologic differentiation (including adenoid, squamous, or other types)
* Patients must have the prespecified a central laboratory or previous test report confirming the presence of a specific FGFR3 mutation or overexpression, FGFR2/3 fusion in tumor tissue or blood based on central laboratory test or previous test reports.
* No prior (or up to one course of chemotherapy) systemic therapy for advanced urothelial carcinoma, or disease progression more than 12 months after the end of the last prior adjuvant therapy, or disease progression or intolerable toxicity after at least one line of standard of care (per local standard of care or guidelines)
* Cohort 3 (non-small cell lung cancer)
* Histologically or cytologically confirmed metastatic/unresectable non-small cell lung cancer (NSCLC)
* Patients must have the prespecified a central laboratory or previous test report confirming the presence of a specific FGFR2/3 mutation, fusion, or overexpression in tumor tissue or blood based on central laboratory test or previous test reports.
* Disease progression or intolerable toxicity after at least one prior line of standard of care or targeted therapy for driver mutations (according to local standards of care or guidelines)
* Cohort 4 (Other Solid Tumors)
* Histologically or cytologically confirmed metastatic/unresectable other solid tumors
* Patients must have a central laboratory or previous test report confirmingthe FGFR2/3 gene activationng alterations (including FGFR2/3 activating mutations, fusions/rearrangements, or FGFR2 amplifications) or overexpression in tumor tissue or blood based on central laboratory test or previous test reports.
* Disease progression or intolerable toxicity after at least one prior line of standard therapy.

Exclusion Criteria:

* Previous treatment with an FGFR pathway inhibitor or a multi-kinase inhibitor designed to inhibit FGFR (consultation with the sponsor is recommended)
* Active or medical history of autoimmune diseases, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. (Patients with type 1 diabetes mellitus, hypothyroidism requiring hormone replacement therapy only, skin diseases that do not require systemic treatment (e.g., vitiligo, psoriasis, or alopecia) are allowed.Uncertain autoimmune-related status should be discussed with the sponsor).
* The patient had clinically symptomatic lung disease (e.g. interstitial pneumonia, pulmonary fibrosis, severe radiation pneumonitis, etc.) requiring systemic corticosteroid therapy within 6 months prior to enrollment.
* Known other malignancies that are in progression or require active treatment (except cured skin cancer, carcinoma in situ of the cervix, basal cell carcinoma, focal prostate cancer with a Gleason score of 6, focal prostate cancer with a Gleason score of 3 + 4 and treated for more than 6 months at screening).
* Time from the end of other prior anti-tumor therapy to the first dose of study drug: major surgery (palliative treatment for local lesions is allowed), in vitro and in vivo radiotherapy (\> 30% bone marrow exposure) is less than 4 weeks; received immunotherapy or other antibody study drugs within 4 weeks prior to the start of study treatment; received chemotherapy (within 6 weeks of the start of study treatment with nitrosourea or mitomycin chemotherapy), endocrine therapy, and small molecule targeted therapy within 2 weeks or 5 half-lives, whichever is shorter.
* Patients who have not recovered to ≤ Grade 1 (CTCAE v5.0) from toxicities caused by prior chemotherapy, radiotherapy, and other anti-tumor therapies, including immunotherapy (except for alopecia as permitted by eligibility criteria or alopecia, vitiligo, stable hypothyroidism controlled by hormone replacement therapy, ≤ Grade 2 hearing loss, or ≤ Grade 2 peripheral neurotoxicity).
* History of ≥ Grade 3 immune-related adverse events with prior therapy.
* (Expansion Cohort 3 (non-small cell lung cancer)) Patients were previously identified with driver mutations (according to local diagnostic and therapeutic criteria or guidelines such as EGFR mutation, ALK rearrangement positive, KRAS G12C mutation positive, NTRK1/2/3 gene fusion positive, RET fusion positive, MET exon 14 skipping mutation, BRAF V600E mutation positive, ROS1 rearrangement positive) and did not receive targeted therapy.

Where this trial is running

Guiyang, Guizhou and 20 other locations

• Guizhou Provincial People'S Hospital — Guiyang, Guizhou, China (Not_yet_recruiting)
• The Affiliated Hospital of Guizhou Medical University — Guiyang, Guizhou, China (Not_yet_recruiting)
• The Fourth Hospital of Hebei Medical University — Shijiazhuang, Heibei, China (Not_yet_recruiting)
• Harbin Medical University Cancer Hospital — Harbin, Heilongjiang, China (Not_yet_recruiting)
• Henan Cancer Hospital — Zhengzhou, Henan, China (Not_yet_recruiting)
• Hunan Central Hospital — Changsha, Hunan, China (Not_yet_recruiting)
• Jiangxi Cance Hospital — Nanchang, Jiangxi, China (Not_yet_recruiting)
• Liaoning Cancer Hospital and Institute — Shenyang, Liaoning, China (Not_yet_recruiting)
• Cancer Hospital of Shandong First Medical University — Jinan, Shandong, China (Not_yet_recruiting)
• ZhongShan Hospital Fudan University — Shanghai, Shanghai Municipality, China (Recruiting)
• Xiangyang Central Hospital — Xiangyang, Sichuang, China (Not_yet_recruiting)
• Changzhi People's Hospital — Changzhi, China (Not_yet_recruiting)
• West China Hospital, Sichuan University — Chengdu, China (Not_yet_recruiting)
• The First Hospital of China Medical University — Hangzhou, China (Not_yet_recruiting)
• Zhejiang Provincial People'S Hospital — Hangzhou, China (Not_yet_recruiting)
• Tianjin Medical University Cancer Institute and Hospital — Tianjin, China (Not_yet_recruiting)
• Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology — Wuhan, China (Not_yet_recruiting)
• First Hospital of Shanxi Medical University — Xi'an, China (Not_yet_recruiting)
• Shanxi Cancer hospital (Shanxi Cancer institute) — Xi'an, China (Not_yet_recruiting)
• First Affiliated Hospital of Xiamen University — Xiamen, China (Not_yet_recruiting)
• The Affiliated Hospital of Xuzhou Medical University — Xuzhou, China (Not_yet_recruiting)

Study contacts

• Principal investigator: Tianshu Liu, Doctor — Fudan University
• Study coordinator: Yuan Lu, Doctor

Conditions HER2-Gastric/Gastroesophageal Junction Cancer; Urothelial Carcinoma; Non-Small Cell Lung Cancer; Solid Tumors