Infigratinib for Solid Tumors

Overseen By The Ohio State University Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sameek Roychowdhury

Must not be taking: CYP3A4 inducers/inhibitors, QT prolonging drugs

Disqualifiers: CNS cancer, Corneal disorder, Cardiac disease, 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: 8

Duration: 6 cycles (approximately 24 weeks)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a drug called infigratinib for individuals with advanced or metastatic solid tumors that have specific FGFR gene changes. FGFR proteins play a role in essential body functions, and mutations can cause these proteins to become overactive, promoting cancer growth. Infigratinib aims to block these proteins, potentially halting cancer cell growth. Suitable candidates have solid tumors with FGFR gene changes and have already undergone at least one standard cancer treatment. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but you cannot take certain drugs that affect liver enzymes (CYP3A4), increase calcium or phosphorus levels, or prolong the QT interval (a heart rhythm measure). You should discuss your current medications with the trial team to see if any need to be adjusted.

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

Research has shown that infigratinib is generally safe. In past studies, most participants took the treatment without major problems. Some studies found it well-tolerated, even in patients with various tumors that have FGFR gene changes. While side effects can occur, data suggest many patients manage them well. Prospective trial participants should discuss any concerns with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Infigratinib is unique because it targets a specific pathway involved in the growth of solid tumors, known as the fibroblast growth factor receptor (FGFR) pathway. This is different from many standard treatments, like chemotherapy, which generally target rapidly dividing cells without such specificity. By honing in on the FGFR pathway, infigratinib has the potential to be more effective and possibly have fewer side effects for patients whose tumors are driven by these genetic alterations. Researchers are excited about infigratinib because it offers a tailored approach, potentially improving outcomes for patients with specific genetic profiles.

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

Participants in this trial will receive infigratinib, which has shown promise in treating certain cancers with FGFR gene mutations. Research indicates that patients taking infigratinib lived an average of 5.8 months without their cancer worsening. Additionally, 75.4% of patients experienced stable disease, meaning their cancer did not progress. Infigratinib also led to tumor shrinkage in 31% of patients in early treatment stages and 24% in later stages. These results suggest that infigratinib can be effective for some patients with advanced solid tumors. ^{5 6 7 8 9}

Who Is on the Research Team?

Sameek Roychowdhury, M.D.

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic solid tumors that have specific FGFR gene mutations. Participants must have tried at least one standard treatment and still show signs of the disease, be able to swallow pills, and comply with study procedures. People can't join if they have primary brain cancer or untreated brain metastases, severe eye disorders, significant tissue calcification, gastrointestinal issues affecting drug absorption, abnormal calcium/phosphate metabolism, recent use of certain drugs including strong CYP3A4 inhibitors/inducers or those prolonging QT interval.

Inclusion Criteria

Evidence of measurable or evaluable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

Able to read and/or understand the details of the study and provide written evidence of informed consent as approved by Institutional Review Board (IRB)/Ethics Committee (EC)

Recovery from adverse events of previous systemic anti-cancer therapies to baseline or grade 1, except for: Alopecia, Stable neuropathy of =< grade 2 due to prior cancer therapy, Able to swallow and retain oral medication, Willing and able to comply with scheduled visits, treatment plan and laboratory tests

Exclusion Criteria

Any other medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures

Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral infigratinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)

Current evidence of endocrine alterations of calcium/phosphate homeostasis, e.g., parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis etc

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive infigratinib orally once daily on days 1-21 of each 28-day cycle

6 cycles (approximately 24 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year post-treatment

Every 8 weeks until disease progression, then every 4 months for 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Infigratinib

Trial Overview The trial tests Infigratinib's effectiveness on patients with advanced solid tumors harboring FGFR gene mutations. It aims to see if this oral medication can stop tumor growth by inhibiting over-active FGFR proteins caused by these genetic changes.

How Is the Trial Designed?

Group I: Treatment (infigratinib) Experimental Treatment 1 Intervention

Patients receive infigratinib PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Sameek Roychowdhury

Lead Sponsor

Trials

3

Recruited

40+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8610935/

Infigratinib: First Approval - PMC - PubMed Central Median progression-free survival (PFS) was estimated at 5.8 months (95% CI 4.3–7.6 months) and the disease control rate was 75.4% (95% CI 62.7–85.5%) [14]. At a ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9460895/

Infigratinib in Early-Line and Salvage Therapy for FGFR3 ... Objective response rates were 31% (early-line setting) and 24% (≥2nd-line setting). Infigratinib has notable activity in mUC regardless of line of therapy.

3. bridgebio.com bridgebio.com/news/bridgebio-pharma-and-lianbio-announce-first-patient-treated-in-phase-2a-trial-of-infigratinib-in-patients-with-gastric-cancer-and-other-advanced-solid-tumors/

First Patient Treated in Trial of Infigratinib These results, published in Cancer Discovery, demonstrated tumor regression in multiple in vivo FGFR2 amplified gastric models.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.3_suppl.265

Final results from a phase II study of infigratinib (BGJ398) ... Conclusions: Infigratinib is associated with promising anticancer activity and a manageable AE profile in patients with advanced, refractory CCA ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04233567?term=AREA%5BBasicSearch%5D(INFIGRATINIB)&rank=6

Infigratinib for the Treatment of Advanced or Metastatic ... This phase II trial studies how well infigratinib works in treating solid tumors that have spread to other places in the body (advanced or metastatic) in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10676333/

Pharmacovigilance Study of Infigratinib: A Safety Analysis ... Several clinical trials have provided evidence of infigratinib's promising clinical activity and manageable safety profile in previously ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2021/214622Orig1s000MultidisciplineR.pdf

214622Orig1s000 - accessdata.fda.gov ... infigratinib in Asian patients with solid tumors with ... Data from these studies allow for an informed assessment of the safety profile of infigratinib.

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2468125321001965

Articles Infigratinib (BGJ398) in previously treated patients ... Infigratinib has shown single-agent activity and a manageable safety profile against tumours with FGFR alterations in early clinical studies.24. We aimed to ...

9. nejm.org nejm.org/doi/full/10.1056/NEJMc2504219

Oral Infigratinib Therapy in Children with Achondroplasia The clinical development of infigratinib in children with achondroplasia includes the evaluation of its safety and efficacy at younger ages, ...