Non-Small Cell Lung Cancer (NSCLC)
Conditions
Keywords
Advanced Non-Small Cell Lung Cancer (NSCLC), fibroblast growth factor receptor (FGFR), FGFR1-3 mutations, FGFR1-3 fusions, FGFR1-3 rearrangements, squamous NSCLC, nonsquamous NSCLC, relapsed or refractory
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
Interventions
DRUGPemigatinib
13.5 mg tablet
Sponsors
Incyte Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants enrolled in this study will be assigned to 1 of 2 cohorts: Cohort A (squamous NSCLC) will enroll approximately 100 participants, and Cohort B (nonsquamous NSCLC) will enroll approximately 25 participants.
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
France, Germany, Italy, Spain, United States
Participant flow
Pre-assignment details
This study was conducted at 8 study centers in Spain, Italy, France, and the United States.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A: Squamous NSCLC Participants with squamous non-small cell lung cancer (NSCLC) with known or likely fibroblast growth factor receptor 1, 2, or 3 (FGFR1-3) driver mutations outside the kinase domain or fusions/rearrangements self-administered pemigatinib 13.5 milligrams (mg) (starting dose) as a once daily (QD) oral treatment on a 21-day cycle. Participants took study drug every day on an intermittent dose regimen (2 weeks on treatment, followed by no study drug for 1 week \[dose holiday\]), until documented disease progression or unacceptable toxicity was reported. | 3 |
| Cohort B: Nonsquamous NSCLC Cohort B: Nonsquamous NSCLC (Experimental) Participants with nonsquamous NSCLC with known or likely FGFR1-3 driver mutations outside the kinase domain or fusions/rearrangements, including participants who had relapsed on prior targeted therapy, self-administered pemigatinib 13.5 mg (starting dose) as a QD oral treatment on a 21-day cycle. Participants took study drug every day on an intermittent dose regimen (2 weeks on treatment, followed by no study drug for 1 week \[dose holiday\]), until documented disease progression or unacceptable toxicity was reported. | 5 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 4 |
| Overall Study | Study Terminated by Sponsor | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Cohort A: Squamous NSCLC | Cohort B: Nonsquamous NSCLC | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 0 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 5 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 3 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 4 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 4 / 5 | 5 / 8 |
| other Total, other adverse events | 3 / 3 | 5 / 5 | 8 / 8 |
| serious Total, serious adverse events | 0 / 3 | 2 / 5 | 2 / 8 |
Outcome results
Primary
Objective Response Rate (ORR) in Cohort A
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.
Time frame: up to 267 days
Population: Full Analysis Population: all enrolled participants who received at least 1 dose of pemigatinib. The confidence interval was calculated based on the exact method for binomial distribution.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Squamous NSCLC | Objective Response Rate (ORR) in Cohort A | 33.3 percentage of participants |
Secondary
Duration of Response (DOR) in Cohort A
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.
Time frame: up to 182 days
Population: Full Analysis Population. Only those participants with available data were analyzed. The 95% confidence interval was calculated using the Brookmeyer and Crowley's method.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Squamous NSCLC | Duration of Response (DOR) in Cohort A | NA months |
Secondary
Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
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.
Time frame: up to 302 days
Population: Safety Population: all enrolled participants who received at least 1 dose of pemigatinib
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A: Squamous NSCLC | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 3 Participants |
| Cohort B: Nonsquamous NSCLC | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 5 Participants |
Secondary
Number of Participants With Any Treatment-related TEAE According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0
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.
Time frame: up to 302 days
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A: Squamous NSCLC | Number of Participants With Any Treatment-related TEAE According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 | 3 Participants |
| Cohort B: Nonsquamous NSCLC | Number of Participants With Any Treatment-related TEAE According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 | 5 Participants |
Secondary
ORR in Cohort B
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.
Time frame: up to 80 days
Population: Full Analysis Population. The confidence interval was calculated based on the exact method for binomial distribution.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort B: Nonsquamous NSCLC | ORR in Cohort B | 0.0 percentage of participants |
Secondary
Overall Survival (OS) in Cohort A
OS was defined as the time from the first dose of study treatment to death of any cause.
Time frame: up to 267 days
Population: Full Analysis Population. The 95% confidence interval was calculated using the Brookmeyer and Crowley's method.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Squamous NSCLC | Overall Survival (OS) in Cohort A | NA months |
Secondary
Progression-free Survival (PFS) in Cohort A
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.
Time frame: up to 267 days
Population: Full Analysis Population. The 95% confidence interval was calculated using the Brookmeyer and Crowley's method.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Squamous NSCLC | Progression-free Survival (PFS) in Cohort A | 8.31 months |