A Phase Ia/Ib Study of the Combination of the FGFR inhibitor Pemigatinib and the EGFR inhibitor Afatinib in Advanced Refractory Solid Tumors

Study Name
	A Phase Ia/Ib Study of the Combination of the FGFR inhibitor Pemigatinib and the EGFR inhibitor Afatinib in Advanced Refractory Solid Tumors
ClinicalTrials.gov Identifier (if applicable)
	NCT06302621
Clinical Trial Category (check all that apply)
	Beyond First Line Therapy Targeted Therapy
Study Center
Institution Name
	Massachusetts General Hospital
Institution Address
	55 Fruit Street
City
	Boston
State
	Massachusetts
Zip Code
	02114
Country
	United States
Phone
	(617) 643-1765
Website
	https://www.massgeneral.org/cancer-center/clinical-trials-and-research/termeer-center
Study Contacts
Principal Investigator
	Haley Ellis, MD
P.I. Phone
	(617) 724-4000
P.I. Email
	hellis@mgh.harvard.edu
List additional Principal Investigators (include phone number and email)
	Andreas Varkaris, MD
Study Coordinator
	Susan Waddick, BS, RN OCN
Study Coordinator Phone
	(617) 643-1765
Study Coordinator Email
	swaddick@mgh.harvard.edu
OVERVIEW – in layman’s terms (150 words max)
	Studying the combination of pemigatinib and afatinib in patients with FGFR-altered advanced solid tumors, including cholangiocarcinoma. Preclinical work demonstrates this combination is effective in overcoming treatment resistance by blocking bypass growth pathways. Patients with and without prior FGFR inhibitor treatment are eligible.
Enrollment
	40
Study Start Date
	04/01/2024
Estimated Completion Date
	04/01/2026
Purpose of the Study – in Layman’s Terms (use the “+” to add more list items)
	Safety Tolerability Efficacy
Inclusion Criteria – Patients Must:
	Unresectable or metastatic, histologically confirmed advanced solid tumor, where standard curative or palliative measures are no longer effective or are not considered appropriate/safe FGFR1-3 fusion, rearrangement, activating mutation, or FGFR2 extracellular domain in-frame deletions on tumor profiling Eastern Cooperative Oncology Group (ECOG) 0-1 At least 18 years of age Ability to swallow tablets Life expectancy >/=3 months Ability to comply with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation Patients with cholangiocarcinoma must have adequate biliary drainage (per investigator’s discretion), with no evidence of ongoing infection Willingness of men and women of reproductive potential to observe conventional and effective birth control for the duration of treatment and for 3 months following the last dose of study treatment Measurable or non-measurable disease as determined by RECIST 1.1 Adequate organ function
Exclusion Criteria – Patients Must NOT:
	For patients treated with a prior FGFR inhibitor, there is a list of excluded secondary FGFR2 kinase domain mutations. Please discuss with the study coordinator and PI. Systemic or liver-directed anticancer therapy within 2 weeks; or anticancer monoclonal antibody within 4 weeks prior to planned start of pemigatinib and afatinib Patient has adverse events from prior therapy that have not resolved to ≤ grade 1; exceptions for non-clinically meaningful AEs can be made with input from the principal investigator Major surgery within 4 weeks prior to planned start of pemigatinib and afatinib (tumor biopsy, biliary stent or catheter placement, and feeding tube placement are not considered major surgical procedures) Received prior palliative non-CNS radiation within 2 weeks or extended-field radiation administered within 4 weeks of first dose of study drug. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. Fibrotic pulmonary disease from prior radiotherapy is permissible with approval of the study PI Known pre-existing interstitial lung disease Current hypovitaminosis D requiring supraphysiologic (eg 50,000 IU/weekly) to replenish the deficiency. Vitamin D supplements are allowed. History and/or current evidence of clinically significant ectopic mineralization/calcification or non-tumor related alteration of calcium-phosphorus homeostasis. History and/or current evidence of clinically significant corneal or retinal disorder confirmed by ophthalmological examination Child-Pugh B and C cirrhosis Chronic nausea, vomiting, or diarrhea considered to be clinically significant in the opinion of the investigator. This includes significant or recent gastrointestinal disorders with diarrhea as a major symptom. Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drug Patients with a history of another primary malignancy that is currently clinically significant, and has potential for metastases or currently requires active intervention (except for gonadotropin-releasing hormone (GnRH) or luteinizing hormone-releasing hormone (LH-RH) agonists in prostate cancer or hormonal therapy in breast cancer Have history of hepatic encephalopathy of any grade Active central nervous system (CNS) metastases are not eligible. Patients with asymptomatic and treated brain metastases may participate provided that they are stable for ≥ 2 months. Patients with suspected or confirmed leptomeningeal disease are not eligible even if treated. Patients with gliblastoma multiforme (GBM) are not eligible. Clinically significant, active cardiovascular disease such as uncontrolled hypertension, congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia, or history of myocardial infarction within 6 months prior to planned start of pemigatinib and afatinib Active uncontrolled systemic bacterial, viral, fungal or parasitic infection (except for fungal nail infection), or other clinically significant active disease process which in the opinion of the investigator and the sponsor-investigator makes it undesirable for the patient to participate in the trial. Screening for chronic conditions is not required.
REQUIRED TESTS PRIOR TO BEGINNING STUDY TREATMENT – in layman’s terms
	Tissue/tumor and liquid biopsies
POTENTIAL SIDE-EFFECTS – in layman’s terms
	Decreased appetite Diarrhea Dry eyes, mouth, nose, skin Eye issues, including blurry vision and retinal detachment (reversible) Fatigue Hair thinning or loss Hand-foot syndrome High phosphorus Mouth sores Nail and skin changes Nausea/vomiting Rash Taste changes
Financial Assistance is available to participants for travel, lodging, etc.
	No