A Phase 2 Study of Lirafugratinib in Non-CCA Solid Tumors With FGFR2 Fusion or Rearrangement

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Elevar Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-07-09

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Elevar Therapeutics Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Dose response, Pharmacokinetic, Safety, Efficacy, Pharmacodynamic

To evaluate the efficacy of lirafugratinib by ORR assessed by IRC

Secondary objectives 6

1. 1. To determine the DOR of lirafugratinib assessed by IRC
2. 2. To evaluate the safety and tolerability of lirafugratinib
3. 3. To evaluate the additional antitumor activity of lirafugratinib
4. 4. To evaluate the PK of lirafugratinib
5. 5. To evaluate the ER of lirafugratinib for efficacy and safety
6. 6. To evaluate the QoL

Conditions and MedDRA coding

Previously Treated, Unresectable, Locally Advanced or Metastatic Solid Tumors (Excluding Cholangiocarcinoma) With FGFR2 Fusion or Rearrangement

Study design 3 periods

Regulatory references

Plan to share IPD

No

IPD plan description

Further assessment by our data protection team at Elevar is currently in progress

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1. Subject is willing and able to provide informed consent for the study prior to the performance of any study-specific procedures.
2. 2. Male or female subject ≥18 years of age.
3. 3. Subject has a measurable disease per RECIST v1.1.
4. 4. Subject has unresectable, locally advanced, or metastatic solid tumor (other than CCA) with FGFR2 f/r as detected by DNA or RNA sequencing or break-apart fluorescence in situ hybridization (defined in Appendix H), per local assessment of blood and/or tumor.
5. 5. Subject has been previously (>30 days) treated with ≥1 line of systemic therapy including chemotherapy (e.g., gemcitabine/cisplatin), immunotherapy, radiation therapy, or other approved therapies.
6. 6. Subject has not received prior treatment with an FGFRi.
7. 7. Subject has an ECOG performance status of 0 or 1.

Exclusion criteria 20

1. 1. Subject has uncontrolled comorbidity.
2. 2. Subject has cancer other than FGFR2 f/r and has a known primary driver alteration that is amenable to approved targeted therapy (e.g., EGFR, ALK, ROS1, RET, HER2, BRAF, IDH1, KRAS). However, the subject may be eligible after consultation with the Sponsor.
3. 3. Subject does not have the following adequate organ function assessments within 7 days prior to the first dose of lirafugratinib: a. Platelet count ≥75×109/L (platelet transfusion may be used to reach 75×109/L but must have been administered at least 2 weeks prior to the first dose of lirafugratinib) b. Absolute neutrophil count ≥1×109/L c. Hemoglobin ≥8 g/dL (red blood cell transfusion and erythropoietin may be used to reach 8 g/dL but must have been administered at least 2 weeks prior to the first dose of lirafugratinib) d. Aspartate aminotransferase or alanine aminotransferase <3× the upper limit of normal (ULN) if no hepatic metastases are present and <5×ULN if hepatic metastases are present e. Total bilirubin <1.5×ULN; <3×ULN, with direct bilirubin <1.5×ULN in the presence of Gilbert’s disease f. Estimated (including Cockcroft-Gault, Modification of Diet in Renal Disease [MDRD] or Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formulas [Appendix A]) or measured creatinine clearance >50 mL/min g. Serum phosphate <7.0 mg/dL (2.3 mmol/L)
4. 4. Subject has an active infection, including human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV) infectia. a. Active HIV infection is defined by positivity for HIV-1 or HIV-2 antibodies. Subjects who are HIV positive are allowed if all of the following criteria are met: CD4+ count ≥350/μL, undetectable viral load, receiving antiretroviral therapy (ART) that does not interact with lirafugratinib (subjects should be on established ART for at least 4 weeks), and no HIV/acquired immunodeficiency syndrome-associated opportunistic infection in the last 12 months (Uldrick 2017). b. Active HBV infection is defined by a positive HBV surface antigen (HBsAg) result. Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core [HBc] antibody, absence of HBsAg, and serum HBV DNA <1000 IU/mL) are eligible (Reddy 2014, Terrault 2018). Subjects with well-controlled HBV infection, indicated by presence of HBsAg with serum HBV DNA <500 IU/mL are also eligible. c. Subjects positive for HCV antibody are eligible only if the polymerase chain reaction is negative for HCV RNA.
5. 5. Subject has a QT interval corrected using Fridericia’s formula >480 msec or a history of prolonged QT syndrome or Torsade de Pointes or a family history of prolonged QT syndrome.
6. 6. Subject has clinically significant, uncontrolled cardiovascular disease, including congestive heart failure Class III or IV according to the New York Heart Association classification; myocardial infarction or unstable angina within the previous 6 months; uncontrolled hypertension (Grade 3 or higher); or clinically significant, uncontrolled arrhythmia, including bradyarrhythmia that may cause QT prolongation (e.g., type II second-degree heart block or third-degree heart block).
7. 7. Subject has central nervous system (CNS) metastases or primary CNS tumor that is associated with progressive neurologic symptoms or requires increasing doses of corticosteroids to control the CNS disease. If a subject requires corticosteroids for management of CNS disease, the dose of corticosteroids must have been stable for the 2 weeks preceding C1D1. Subjects with stable or asymptomatic CNS metastases or primary CNS tumor may be eligible after consultation with the Sponsor.
8. 8. Subject has received anticancer therapy (including both systemic therapy and radiotherapy) within 14 days or 5 half-lives (whichever is shorter) and immunotherapy or other antibody therapy within 28 days prior to the first dose of lirafugratinib. Lirafugratinib may be started within these washout periods if considered by the Investigator to be safe and in the best interest of the subject, with prior Sponsor approval, provided immune-related toxicities in subjects who received previous immunotherapy have resolved to
9. 9. Subject has received locoregional hepatic therapy (e.g., transcatheter arterial chemoembolization or yttrium90) within 4 weeks prior to C1D1.
10. 10. Subject has received neutrophil growth factor support within 14 days of the first dose of lirafugratinib.
11. 11. Subject requires treatment with a prohibited medication (Section 6.8.1) that cannot be discontinued at least 5 half-lives or 2 weeks (whichever is shorter) before the initiation of lirafugratinib.
12. 12. Subject has had a major surgical procedure within 14 days of the first dose of lirafugratinib (procedures such as central venous catheter placement and tumor needle biopsy are not considered major surgical procedures). Study centers should discuss other minor surgeries with the Sponsor.
13. 13. Subject has a history of another primary malignancy that has been diagnosed or required therapy within the past year. The following prior malignancies are not exclusionary: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate or breast cancer, curatively treated localized thyroid cancer, and completely resected carcinoma in situ of any site. Adjuvant hormonal therapy for previously treated breast cancer, prostate cancer, or another hormone-dependent solid tumor is not exclusionary.
14. 14. Subject is unwilling or unable to comply with scheduled visits, drug dosing regimen, laboratory tests, or other study procedures and study restrictions.
15. 15. Female subjects, if not postmenopausal or surgically sterile, are unwilling to abstain from sexual intercourse or employ highly effective contraception during the treatment period and for at least 180 days (6 months) after the last dose of lirafugratinib. Male subjects, if not surgically sterile, are unwilling to abstain from sexual intercourse or employ highly effective contraception during the treatment period and for at least 90 days (3 months) after the last dose of lirafugratinib.
16. 16. Pregnant female subjects, as documented by a serum beta human chorionic gonadotropin (β-hCG) pregnancy test consistent with pregnancy, obtained within 7 days prior to the first dose of lirafugratinib. Females with β-hCG values that are within the range for pregnancy but are not pregnant (false positives) may be enrolled with written consent of the Sponsor after pregnancy has been ruled out. Female subjects of nonchildbearing potential (postmenopausal for more than 1 year; bilateral tubal ligation; bilateral oophorectomy; total hysterectomy) do not require a serum β-hCG test.
17. 17. Female subjects who are breastfeeding.
18. 18. Subject has prior or ongoing clinically significant disease, medical condition, surgical history, physical finding, or laboratory abnormality that, in the Investigator’s opinion, could affect the safety of the subject; alter the absorption, distribution, metabolism, or excretion of lirafugratinib; or impair the assessment of study results.
19. 19. Subject has documented history of and/or ongoing clinically significant ectopic mineralization/calcification.
20. 20. Subject has known systemic hypersensitivity to lirafugratinib drug substance or inactive ingredients.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. ORR assessed by IRC per RECIST v1.1

Secondary endpoints 6

1. DOR assessed by IRC per RECIST v1.1
2. • Incidence, severity, and causality of TEAEs, treatment-related TEAEs, SAEs, AESIs, clinically significant change from baseline in laboratory values, ECG, vital signs, and other safety findings judged according to NCI CTCAE v5.0 from the first dose of lirafugratinib to the last Safety Follow-Up Visit • Dose intensity • Dose modifications (i.e., dose interruption, dose reduction, and dose discontinuation) • Concomitant treatment of ADRs
3. • ORR and DOR assessed by Investigator per RECIST v1.1 • DCR and PFS assessed by Investigator and IRC per RECIST v1.1 • OS • PFS and OS rates at 6, 9, and 12 months, assessed by Investigator and IRC • TTR and TTP assessed by Investigator and IRC per RECIST v1.1
4. Plasma concentration summary and separate population PK analysis of lirafugratinib
5. ER for efficacy and safety if the PK, efficacy, and safety of lirafugratinib are substantially different from the previous observations
6. • QoL assessed by EORTC QLQ-C30 • TTD, defined as time from the first dose of lirafugratinib to first deterioration (a score decrease of ≥10 from baseline) maintained for 2 consecutive timepoints, or one timepoint followed by death (from any cause) within 4 weeks

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Elevar Therapeutics Inc.

Sponsor organisation

Elevar Therapeutics Inc.

Address

1 Bridge Plaza North Suite 850

City

Fort Lee

Postcode

07024-7101

Country

United States

Scientific contact point

Organisation

Elevar Therapeutics Inc.

Contact name

Regulatory Affairs

Public contact point

Organisation

Elevar Therapeutics Inc.

Contact name

Regulatory Affairs

Third parties 21

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 32 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications