Study to Evaluate the Efficacy and Safety of Pemigatinib in Participants With Relapsed or Refractory Advanced Non-Small Cell Lung Cancer With an FGFR Alteration
- Registration Number
- NCT05253807
- Lead Sponsor
- Incyte Corporation
- Brief Summary
This is an open-label, single arm study to study the safety, efficacy and tolerability of Pemigatinib when used on participants with squamous or nonsquamous NSCLC with a documented FGFR1-3 mutations or fusions/rearrangement who have progressed on prior therapies and have no available standard treatment options
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 8
- Histologically or cytologically confirmed advanced or metastatic NSCLC (Stage IIIB/C or IV per the AJCC Cancer Staging Manual, 8th Edition). Both squamous and nonsquamous NSCLC are eligible.
- Radiographically measurable disease (per RECIST v1.1). Tumor lesions located in a previously irradiated area, or in an area subjected to other loco-regional therapy, are considered measurable if progression has been clearly demonstrated in the lesion.
- Documentation of known/likely actionable known or likely FGFR1-3 alterations.
- Must have objective documented progression after at least 1 prior therapy, and must have no therapy available that is likely to provide clinical benefit. Participants who are intolerant of or decline the approved therapy are eligible only if they have no therapy available that is likely to provide clinical benefit.
- ECOG performance status of 0 to 2.
- Baseline archival tumor specimen (if less than 24 months from date of screening) or willingness to undergo a pretreatment tumor biopsy to obtain the specimen. Must be a tumor block or approximately 15 unstained slides from biopsy or resection of primary tumor or metastasis.
- Willingness to avoid pregnancy or fathering a child.
Exclusion Criteria
- Prior receipt of a selective FGFR inhibitor.
- Receipt of anticancer medications or investigational drugs for any indication or reason within 28 days before the first dose of pemigatinib. Participants must have recovered (≤ Grade 1 as per CTCAE v5.0 or at pretreatment baseline) from AEs from previously administered therapies (excluding alopecia).
- Concurrent anticancer therapy (eg, chemotherapy, immunotherapy, biologic therapy, hormonal therapy, or investigational therapy).
- Candidate for potentially curative surgery.
- Current evidence of clinically significant corneal (including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, and keratoconjunctivitis) or retinal disorder (including but not limited to macular/retinal degeneration, diabetic retinopathy, and retinal detachment) as confirmed by ophthalmologic examination.
- Radiation therapy administered for the treatment of cancer lesions within 2 weeks before enrollment/first dose of study drug. Participants must have recovered from all radiation related toxicities, not require corticosteroids, and not have had radiation pneumonitis. Evidence of fibrosis within a radiation field from prior radiotherapy is permitted with medical monitor approval. A 1-week washout is permitted for palliative radiation to non-CNS disease.
- Untreated brain or CNS metastases or brain or CNS metastases that have progressed (eg, evidence of new or enlarging brain metastasis or new neurological symptoms attributable to brain or CNS metastases). Participants who have previously treated and clinically stable brain or CNS metastases are eligible if there is no evidence of progression for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT scan) during the screening period, and if they are on a stable or decreasing dose of corticosteroids for at least 1 week.
- Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
- Participants with defined laboratory values at screening.
- History of calcium and phosphate hemostasis disorder or systemic mineral imbalance with ectopic calcification of soft tissues (exception: commonly observed calcifications in soft tissues such as the skin, kidney tendon, or vessels due to injury, disease, or aging in the absence of systemic mineral imbalance).
- History of hypovitaminosis D requiring supraphysiologic doses (eg, 50,000 UI/weekly) to replenish the deficiency. Vitamin D supplements are allowed.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort A: Squamous NSCLC Pemigatinib Participants with squamous NSCLC with known or likely FGFR1-3 driver mutations outside the kinase domain or fusions/rearrangements will receive intermittent dosing. Cohort B: Non-squamous NSCLC Pemigatinib Participants with non-squamous NSCLC with known or likely FGFR1-3 driver mutations outside the kinase domain or fusions/rearrangements will receive intermittent dosing.
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) in Cohort A up to 267 days ORR was defined as the percentage of participants who achieved a complete response (CR) or a partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Response was determined by an Independent Central Radiology (ICR) review. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions.
- Secondary Outcome Measures
Name Time Method Progression-free Survival (PFS) in Cohort A up to 267 days PFS was defined as the time from the first dose of study treatment until progressive disease (PD) (according to RECIST v1.1 as assessed by an ICR review) or death, whichever occurred first. PD was defined as the progression of a target or non-target lesion or presence of a new lesion.
Overall Survival (OS) in Cohort A up to 267 days OS was defined as the time from the first dose of study treatment to death of any cause.
ORR in Cohort B up to 80 days ORR was defined as the percentage of participants who achieved a CR or PR based on RECIST v1.1. Response was determined by an ICR review. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions.
Duration of Response (DOR) in Cohort A up to 182 days DOR was defined as the time from the date of the first CR or PR until the date of the first PD (according to RECIST v1.1 as assessed by an ICR review) or death, whichever occurred first. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion.
Number of Participants With Any Treatment-emergent Adverse Event (TEAE) up to 302 days An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug-related. An AE could therefore have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. A TEAE was defined as an AE that was reported for the first time or the worsening of a pre-existing event after the first dose of pemigatinib and within 30 days of the last dose of pemigatinib.
Number of Participants With Any Treatment-related TEAE According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 up to 302 days An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug-related. An AE could therefore have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. A TEAE was defined as an AE that was reported for the first time or the worsening of a pre-existing event after the first dose of pemigatinib and within 30 days of the last dose of pemigatinib. The investigator assessed the relationship between study drug and each occurrence of each AE/serious adverse event.
Trial Locations
- Locations (36)
Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Valkyrie Clinical Trials
🇺🇸Los Angeles, California, United States
Florida Cancer Specialists & Research Institute
🇺🇸Fort Myers, Florida, United States
Miami Cancer Institute
🇺🇸Miami, Florida, United States
Memorial Healthcare System
🇺🇸Pembroke Pines, Florida, United States
University of Kentucky Hospital
🇺🇸Lexington, Kentucky, United States
Chu de Toulouse Hopital Larrey Centre de Reference Des Maladies Rares de La Peau Service de Dermatol
🇫🇷Toulouse, France
Spoknwrd Clinical Trials Inc.
🇺🇸Easton, Pennsylvania, United States
H�PITAL NORD - CHU MARSEILLE
🇫🇷Marseille Cedex 5, France
Zentralklinik Bad Berka Gmbh
🇩🇪Bad Berka, Germany
Lungenklinik Hemer
🇩🇪Hemer, Germany
University Hospital Mannheim
🇩🇪Mannheim, Germany
Lki Lungenfachklinik Immenhausen
🇩🇪Immenhausen, Germany
Irccs Centro Di Riferimento Oncologico
🇮🇹Aviano, Italy
Istituto Tumori Giovanni Paolo Ii Irccs Ospedale Oncologico Bari
🇮🇹Bari, Italy
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori
🇮🇹Meldola, Italy
Azienda Ospedaliera Universitaria San Luigi Gonzaga Orbassano
🇮🇹Orbassano, Italy
Hospital Regional Universitario de Malaga
🇪🇸Malaga, Spain
Azienda Ospedaliera Di Perugia - Ospedale Santa Maria Della Misericordia
🇮🇹Perugia, Italy
Azienda Ospedaliero Universitaria Pisana
🇮🇹Pisa, Italy
Istituto Nazionale Tumori Regina Elena Irccs
🇮🇹Roma, Italy
Irccs Istituto Clinico Humanitas
🇮🇹Rozzano, Italy
Complejo Hospitalario Universitario A Coruna
🇪🇸A Coru?a, Spain
Hospital de La Santa Creu I Sant Pau
🇪🇸Barcelona, Spain
Ico Girona Hospital Universitari de Girona Dr Josep Trueta
🇪🇸Girona, Spain
Hospital General Universitario Vall D Hebron
🇪🇸Barcelona, Spain
Hospital Universitario Ciudad de Jaen
🇪🇸Jaen, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Ico Institut Catala D Oncologia
🇪🇸L'hospitalet de Llobregat, Spain
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Hospital Universitario Ramon Y Cajal
🇪🇸Madrid, Spain
Hospital Universitario de La Paz
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Hospital Universitario Hm Sanchinarro
🇪🇸Madrid, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain