Squamous-Cell Non-Small-Cell Lung Cancer
Conditions
Keywords
Squamous-Cell Non-Small-Cell Lung Cancer, FGFR2b-positive Squamous-Cell Non-Small-Cell Lung Cancer, SqNSCLC, Bemarituzumab, Docetaxel
Brief summary
The primary objectives of this study are to evaluate the safety and tolerability of bemarituzumab monotherapy and combination with other anti-cancer therapies, and to determine the recommended phase 3 dose of bemarituzumab in combination with other anti-cancer therapies.
Interventions
DRUGPaclitaxel
IV infusion
DRUGNab-paclitaxel
IV infusion
DRUGBemarituzumab
Intravenous (IV) infusion
DRUGDocetaxel
IV infusion
DRUGPembrolizumab
IV infusion
DRUGCarboplatin
IV infusion
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Participant has provided informed consent/assent prior to initiation of any study specific activities/procedures * Age ≥ 18 years old (or legal adult within country, whichever is older) at the time that the Informed Consent Form (ICF) is signed * Pathologically confirmed squamous cell lung carcinoma * Disease that is unresectable, locally advanced or metastatic (not amenable to curative therapy) * Participants must have archived tumor tissue sample (formalin fixed, paraffin embedded \[FFPE\] sample \[FFPE of excisional, or core needle\]) taken within last 5 years or be willing to undergo pre-treatment tumor biopsy (excisional, or core needle) for tissue prior to enrollment * Participant must have progressed on, or recurred after at least 1 prior systemic therapy (Part 1 and 2 only) or at least 2 prior systemic therapies (Part 3 only) for locally advanced and unresectable or metastatic disease. Prior treatment must include a platinum-based doublet chemotherapy and checkpoint inhibitor for advanced or metastatic disease, either given as one line of therapy or as individual lines of therapy, unless the participant has a medical contraindication to one of the required therapies (which must be documented in the electronic case report form \[eCRF\]). Additionally, if the participant's tumor was previously identified as having a driver mutation (according to local standard of care or guidelines, e.g., Kirsten rat sarcoma \[KRAS\] G12C, neurotrophic tyrosine receptor kinase \[NTRK\]), which has an approved therapy for which the participant is eligible and available, the participant must have received the approved therapy in a prior line of treatment. * For Part 4, participants may not have received prior systemic therapy for their locally advanced and unresectable or metastatic disease. For Part 4, participants who received peri-operative systemic therapy are eligible if that adjuvant/neoadjuvant therapy was completed at least 12 months prior to diagnosis of locally advanced and unresectable or metastatic disease. * Measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Adequate organ function as determined per protocol * Part 2, 3 and 4 only: FGFR2b overexpression as determined by centrally performed immunohistochemistry (IHC) testing
Exclusion criteria
* Mixed small-cell lung cancer or mixed non-small cell lung cancer (NSCLC) histology * Untreated or symptomatic central nervous system (CNS) metastases or leptomeningeal disease * Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures at a frequency greater than monthly * Impaired cardiac function or clinically significant cardiac disease including: unstable angina within 6 months prior to first dose of study treatment, acute myocardial infarction \< 6 months prior to first dose of study treatment, New York Heart Association (NYHA) class II-IV congestive heart failure, uncontrolled hypertension (defined as an average systolic blood pressure \>160 mmHg or diastolic \>100 mm Hg despite optimal treatment (measured following European Society for Hypertension/European Society of Cardiology \[ESH/ESC\] 2013 guidelines; Section 11.11), uncontrolled cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin, active coronary artery disease, Fridericia's correction formula (QTc) ≥ 470 * Evidence of any ongoing ophthalmologic abnormalities or symptoms that are acute (within 4 weeks) or actively progressing * Recent (within 6 months) corneal surgery or ophthalmic laser treatment or recent (within 6 months) history of, or evidence of, corneal defects, corneal ulcerations, keratitis, or keratoconus, or other known abnormalities of the cornea that may pose an increased risk of developing a corneal ulcer * Part 1 and Part 2: participants that experienced toxicity or hypersensitivity requiring discontinuation of prior docetaxel treatment * Part 1 only: participants that had disease progression on prior therapy with docetaxel * Part 2 only: participants have received prior docetaxel in unresectable or metastatic setting (including participants who received prior docetaxel in first line for metastatic disease, but not including participants who received prior docetaxel neoadjuvantly or adjuvantly and did not progress within 6 months of end of therapy) * Prior treatment with any selective inhibitor of the fibroblast growth factor-fibroblast growth factor receptor (FGF-FGFR) pathway
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced a Dose Limiting Toxicity (DLT): Parts 1 and 4 | Day 1 to Day 21 of Cycle 1 (each cycle was 21 days) | DLTs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and included the below if considered by the investigator to be related to study drug, excluding toxicities related to disease progression or intercurrent illness: Grade 3 thrombocytopenia for \> 7 days or with Grade \> 2 bleeding, vomiting/diarrhea for \> 3 days, fatigue; Grade ≥ 3 febrile neutropenia, nausea for \> 3 days; Grade 4 neutropenia, thrombocytopenia, anemia, ophthalmologic AE, laboratory value, vomiting/diarrhea; Grade 5 toxicity (death not due to disease progression). CTCAE Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, and Grade 5 results in death. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Day 1 of cycle 1 to 100 days after the last dose of study treatment or end of study date, whichever occurred earlier (Parts 1, 2, and 4 cycle length = 21 days; Part 3 cycle length = 14 days). Median treatment duration was 6.2 weeks. | An AE was defined as any untoward medical occurrence in a clinical trial participants. TEAEs were any AE that started on or after receiving the first dose of investigational product and up to 28 days after the last dose of investigational product or the end of study date, whichever is earlier. Treatment-related TEAEs were those considered possibly related to study treatment by the investigator. Any clinically significant changes in electrocardiograms, vital signs, physical examination with a neurological assessment, clinical laboratory tests, and visual acuity were recorded as TEAEs. A serious TEAE resulted in death, was immediately life threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or another medically important serious event. AEs of special interest (AESIs) were ocular events of any CTCAE grade or seriousness occurring up to 100 days after the last dose of bemarituzumab. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Observed Concentration at the End of a Dose Interval (Ctrough) of Bemarituzumab | Pre-dose Cycle 2 Day 1 and Cycle 3 day 1 | Bemarituzumab serum concentrations with values below the limit of quantification were set to zero for analysis. PK parameters were determined from the time concentration profile using noncompartmental analysis. |
| Percentage of Participants Who Achieved an Objective Response (OR) | Every 6 (+/- 1) weeks from the first dose of bemarituzumab (cycle 1 day 1) up to week 54, then every 12 (+/- 2 weeks), up to the end of the long term follow-up (LTFU) period (median time on study was approximately 21 weeks) | OR was defined as the best overall response of confirmed complete response (CR) or confirmed partial response (PR) as defined by the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). CR: disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to \<10 mm. All lymph nodes must have been non-pathological in size (\< 10 mm). PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Duration of Response (DOR) | Every 6 (+/- 1) weeks from the first dose of bemarituzumab (cycle 1 day 1) up to week 54, then every 12 (+/- 2 weeks), up to the end of the LTFU period (median time on study was approximately 21 weeks) | DOR was defined as the time from the first documentation of OR (determined by the investigator per RECIST v1.1) until first documentation of disease progression or death due to any cause, whichever occurred first. DOR was censored at the last evaluable post-baseline tumor assessment prior to subsequent anticancer therapy; otherwise, at date of first documentation of OR (i.e., assigned a one-day interval). |
| Area Under the Serum Drug Concentration-time Curve From Time 0 to End of Dosing Interval (AUCtau) of Bemarituzumab | Parts 1, 2, 3, and 4: Cycles 1 and 2 pre-dose, 0.25, 3, 6, 24, 72, 168, 336, 504 (except Part 3) hours post-dose | Bemarituzumab serum concentrations with values below the limit of quantification were set to zero for analysis. Pharmacokinetic (PK) parameters were determined from the time concentration profile using noncompartmental analysis. |
| Progression-free Survival (PFS) | Participants completed the LTFU for survival every 3 months ± 1 month after the safety follow-up visit (at 28 days after the last dose of bemarituzumab), up to the end of the study. Median time on study was approximately 21 weeks | PFS was defined as the time from date of first dose of investigational product until the first documentation of radiologic disease progression or death due to any cause, whichever occurred first, in the absence of subsequent anticancer therapy. PFS was censored at the last evaluable post-baseline tumor assessment prior to subsequent anticancer therapy; otherwise, at first dose of investigational product. Progression was based on RECIST v1.1 criteria. PD: at least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an increase of at least 5 mm. Unequivocal progression of existing non-target lesions. |
| Overall Survival (OS) | Participants completed the LTFU for survival every 3 months ± 1 month after the safety follow-up visit (at 28 days after the last dose of bemarituzumab), up to the end of the study. Median time on study was approximately 21 weeks | OS was defined as the time from the date of first dose of investigational product until event of death due to any cause through the analysis cutoff date. Participants still alive were censored at the date last known to be alive through the analysis cutoff date. |
| Disease Control Rate (DCR) | Every 6 (+/- 1) weeks from the first dose of bemarituzumab (cycle 1 day 1) up to week 54, then every 12 (+/- 2 weeks), up to the end of the LTFU period (median time on study was approximately 21 weeks) | DCR was defined as the percentage of participants documented to have a CR, PR or stable disease (SD) per RECIST v1.1. CR: disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to \<10 mm. All lymph nodes must have been non-pathological in size (\< 10 mm). PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD: at least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an increase of at least 5 mm. Unequivocal progression of existing non-target lesions. |
| Maximum Observed Serum Concentration (Cmax) of Bemarituzumab | Parts 1, 2, 3, and 4: Cycles 1 and 2 pre-dose, 0.25, 3, 6, 24, 72, 168, 336, 504 (except Part 3) hours post-dose | Bemarituzumab serum concentrations with values below the limit of quantification were set to zero for analysis. PK parameters were determined from the time concentration profile using noncompartmental analysis. |
Countries
Belgium, France, Japan, Poland, South Korea, Spain, Taiwan, United States
Participant flow
Recruitment details
A total of 74 participants were enrolled across 8 countries from March 2022 and the last participant last visit was in May 2024.
Pre-assignment details
The study consisted of 4 Parts: * Part 1: Combination dose exploration with docetaxel * Part 2: Combination dose expansion with docetaxel * Part 3: Monotherapy * Part 4: Combination with carboplatin, paclitaxel or nab-paclitaxel, and pembrolizumab. The planned dose levels were dose level 1 (lower) and dose level 2 (higher).
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Bemarituzumab Dose 1 With Docetaxel Participants received multiple IV doses of bemarituzumab dose level 1 and IV docetaxel (cycle length = 21 days). | 4 |
| Part 1: Bemarituzumab Dose 2 With Docetaxel Participants received multiple IV doses of bemarituzumab dose level 2 and IV docetaxel (cycle length = 21 days). | 9 |
| Part 2: Bemarituzumab Dose 2 With Docetaxel Participants who had an overexpression of FGFR2b received multiple IV doses of bemarituzumab dose level 2 and IV docetaxel (cycle length = 21 days). | 29 |
| Part 3: Bemarituzumab Dose 1 Participants who had an overexpression of FGFR2b received multiple IV doses of bemarituzumab dose level 1 (cycle length = 14 days). | 28 |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy Participants who had an overexpression of FGFR2b received multiple IV doses of bemarituzumab dose level 2 in combination with pembrolizumab, carboplatin and either paclitaxel or nab-paclitaxel (cycle length = 21 days). | 4 |
| Total | 74 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Death | 3 | 5 | 8 | 18 | 1 |
| Overall Study | Decision by sponsor | 0 | 3 | 19 | 7 | 3 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 2 | 2 | 0 |
Baseline characteristics
| Characteristic | Part 1: Bemarituzumab Dose 1 With Docetaxel | Part 1: Bemarituzumab Dose 2 With Docetaxel | Part 2: Bemarituzumab Dose 2 With Docetaxel | Part 3: Bemarituzumab Dose 1 | Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 64.0 years STANDARD_DEVIATION 4.5 | 65.9 years STANDARD_DEVIATION 8.5 | 65.3 years STANDARD_DEVIATION 6.2 | 63.0 years STANDARD_DEVIATION 8.2 | 63.0 years STANDARD_DEVIATION 7.9 | 64.3 years STANDARD_DEVIATION 7.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 9 Participants | 27 Participants | 27 Participants | 4 Participants | 71 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 4 Participants | 12 Participants | 12 Participants | 3 Participants | 33 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 1 Participants | 1 Participants | 5 Participants | 0 Participants | 7 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 2 Participants | 4 Participants | 14 Participants | 11 Participants | 1 Participants | 32 Participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 2 Participants | 8 Participants | 0 Participants | 12 Participants |
| Sex: Female, Male Male | 4 Participants | 7 Participants | 27 Participants | 20 Participants | 4 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 4 | 5 / 9 | 8 / 29 | 18 / 28 | 1 / 4 |
| other Total, other adverse events | 4 / 4 | 9 / 9 | 26 / 29 | 23 / 28 | 4 / 4 |
| serious Total, serious adverse events | 4 / 4 | 5 / 9 | 16 / 29 | 8 / 28 | 4 / 4 |
Outcome results
Primary
Number of Participants Who Experienced a Dose Limiting Toxicity (DLT): Parts 1 and 4
DLTs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and included the below if considered by the investigator to be related to study drug, excluding toxicities related to disease progression or intercurrent illness: Grade 3 thrombocytopenia for \> 7 days or with Grade \> 2 bleeding, vomiting/diarrhea for \> 3 days, fatigue; Grade ≥ 3 febrile neutropenia, nausea for \> 3 days; Grade 4 neutropenia, thrombocytopenia, anemia, ophthalmologic AE, laboratory value, vomiting/diarrhea; Grade 5 toxicity (death not due to disease progression). CTCAE Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, and Grade 5 results in death.
Time frame: Day 1 to Day 21 of Cycle 1 (each cycle was 21 days)
Population: The safety analysis set included all participants who received at least one dose of bemarituzumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Bemarituzumab Dose 1 With Docetaxel | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT): Parts 1 and 4 | 0 Participants |
| Part 1: Bemarituzumab Dose 2 With Docetaxel | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT): Parts 1 and 4 | 1 Participants |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT): Parts 1 and 4 | 0 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An AE was defined as any untoward medical occurrence in a clinical trial participants. TEAEs were any AE that started on or after receiving the first dose of investigational product and up to 28 days after the last dose of investigational product or the end of study date, whichever is earlier. Treatment-related TEAEs were those considered possibly related to study treatment by the investigator. Any clinically significant changes in electrocardiograms, vital signs, physical examination with a neurological assessment, clinical laboratory tests, and visual acuity were recorded as TEAEs. A serious TEAE resulted in death, was immediately life threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or another medically important serious event. AEs of special interest (AESIs) were ocular events of any CTCAE grade or seriousness occurring up to 100 days after the last dose of bemarituzumab.
Time frame: Day 1 of cycle 1 to 100 days after the last dose of study treatment or end of study date, whichever occurred earlier (Parts 1, 2, and 4 cycle length = 21 days; Part 3 cycle length = 14 days). Median treatment duration was 6.2 weeks.
Population: The safety analysis set included all participants who received at least one dose of bemarituzumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Bemarituzumab Dose 1 With Docetaxel | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any treatment-related TEAE | 3 Participants |
| Part 1: Bemarituzumab Dose 1 With Docetaxel | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any AESI | 2 Participants |
| Part 1: Bemarituzumab Dose 1 With Docetaxel | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any TEAE | 4 Participants |
| Part 1: Bemarituzumab Dose 1 With Docetaxel | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any treatment-related SAE | 0 Participants |
| Part 1: Bemarituzumab Dose 1 With Docetaxel | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any SAE | 4 Participants |
| Part 1: Bemarituzumab Dose 2 With Docetaxel | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any treatment-related SAE | 0 Participants |
| Part 1: Bemarituzumab Dose 2 With Docetaxel | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any AESI | 6 Participants |
| Part 1: Bemarituzumab Dose 2 With Docetaxel | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any SAE | 5 Participants |
| Part 1: Bemarituzumab Dose 2 With Docetaxel | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any TEAE | 9 Participants |
| Part 1: Bemarituzumab Dose 2 With Docetaxel | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any treatment-related TEAE | 9 Participants |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any treatment-related TEAE | 21 Participants |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any treatment-related SAE | 2 Participants |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any SAE | 16 Participants |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any TEAE | 29 Participants |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any AESI | 17 Participants |
| Part 3: Bemarituzumab Dose 1 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any treatment-related TEAE | 16 Participants |
| Part 3: Bemarituzumab Dose 1 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any SAE | 8 Participants |
| Part 3: Bemarituzumab Dose 1 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any treatment-related SAE | 0 Participants |
| Part 3: Bemarituzumab Dose 1 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any TEAE | 25 Participants |
| Part 3: Bemarituzumab Dose 1 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any AESI | 9 Participants |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any treatment-related SAE | 2 Participants |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any AESI | 2 Participants |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any treatment-related TEAE | 2 Participants |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any TEAE | 4 Participants |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any SAE | 4 Participants |
Secondary
Area Under the Serum Drug Concentration-time Curve From Time 0 to End of Dosing Interval (AUCtau) of Bemarituzumab
Bemarituzumab serum concentrations with values below the limit of quantification were set to zero for analysis. Pharmacokinetic (PK) parameters were determined from the time concentration profile using noncompartmental analysis.
Time frame: Parts 1, 2, 3, and 4: Cycles 1 and 2 pre-dose, 0.25, 3, 6, 24, 72, 168, 336, 504 (except Part 3) hours post-dose
Population: The PK analysis set included all participants who received at least one dose of bemarituzumab and had at least one PK sample collected. Participants with data available at each timepoint are presented.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: Bemarituzumab Dose 1 With Docetaxel | Area Under the Serum Drug Concentration-time Curve From Time 0 to End of Dosing Interval (AUCtau) of Bemarituzumab | Cycle 1 | 3370 day*mcg/mL |
| Part 1: Bemarituzumab Dose 1 With Docetaxel | Area Under the Serum Drug Concentration-time Curve From Time 0 to End of Dosing Interval (AUCtau) of Bemarituzumab | Cycle 2 | 2610 day*mcg/mL |
| Part 1: Bemarituzumab Dose 2 With Docetaxel | Area Under the Serum Drug Concentration-time Curve From Time 0 to End of Dosing Interval (AUCtau) of Bemarituzumab | Cycle 2 | 4850 day*mcg/mL |
| Part 1: Bemarituzumab Dose 2 With Docetaxel | Area Under the Serum Drug Concentration-time Curve From Time 0 to End of Dosing Interval (AUCtau) of Bemarituzumab | Cycle 1 | 5300 day*mcg/mL |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Area Under the Serum Drug Concentration-time Curve From Time 0 to End of Dosing Interval (AUCtau) of Bemarituzumab | Cycle 2 | 4000 day*mcg/mL |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Area Under the Serum Drug Concentration-time Curve From Time 0 to End of Dosing Interval (AUCtau) of Bemarituzumab | Cycle 1 | 3920 day*mcg/mL |
| Part 3: Bemarituzumab Dose 1 | Area Under the Serum Drug Concentration-time Curve From Time 0 to End of Dosing Interval (AUCtau) of Bemarituzumab | Cycle 1 | 2800 day*mcg/mL |
| Part 3: Bemarituzumab Dose 1 | Area Under the Serum Drug Concentration-time Curve From Time 0 to End of Dosing Interval (AUCtau) of Bemarituzumab | Cycle 2 | 3580 day*mcg/mL |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Area Under the Serum Drug Concentration-time Curve From Time 0 to End of Dosing Interval (AUCtau) of Bemarituzumab | Cycle 1 | 3020 day*mcg/mL |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Area Under the Serum Drug Concentration-time Curve From Time 0 to End of Dosing Interval (AUCtau) of Bemarituzumab | Cycle 2 | 2340 day*mcg/mL |
Secondary
Disease Control Rate (DCR)
DCR was defined as the percentage of participants documented to have a CR, PR or stable disease (SD) per RECIST v1.1. CR: disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to \<10 mm. All lymph nodes must have been non-pathological in size (\< 10 mm). PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD: at least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an increase of at least 5 mm. Unequivocal progression of existing non-target lesions.
Time frame: Every 6 (+/- 1) weeks from the first dose of bemarituzumab (cycle 1 day 1) up to week 54, then every 12 (+/- 2 weeks), up to the end of the LTFU period (median time on study was approximately 21 weeks)
Population: The safety analysis set included all participants who received at least one dose of bemarituzumab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Bemarituzumab Dose 1 With Docetaxel | Disease Control Rate (DCR) | 75.0 percentage of participants |
| Part 1: Bemarituzumab Dose 2 With Docetaxel | Disease Control Rate (DCR) | 66.7 percentage of participants |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Disease Control Rate (DCR) | 65.5 percentage of participants |
| Part 3: Bemarituzumab Dose 1 | Disease Control Rate (DCR) | 53.6 percentage of participants |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Disease Control Rate (DCR) | 75.0 percentage of participants |
Secondary
Duration of Response (DOR)
DOR was defined as the time from the first documentation of OR (determined by the investigator per RECIST v1.1) until first documentation of disease progression or death due to any cause, whichever occurred first. DOR was censored at the last evaluable post-baseline tumor assessment prior to subsequent anticancer therapy; otherwise, at date of first documentation of OR (i.e., assigned a one-day interval).
Time frame: Every 6 (+/- 1) weeks from the first dose of bemarituzumab (cycle 1 day 1) up to week 54, then every 12 (+/- 2 weeks), up to the end of the LTFU period (median time on study was approximately 21 weeks)
Population: The safety analysis set included all participants who received at least one dose of bemarituzumab. Only participants who had achieved OR were evaluated for DOR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Bemarituzumab Dose 2 With Docetaxel | Duration of Response (DOR) | 5.5 months |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Duration of Response (DOR) | 2.8 months |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Duration of Response (DOR) | 4.5 months |
Secondary
Maximum Observed Serum Concentration (Cmax) of Bemarituzumab
Bemarituzumab serum concentrations with values below the limit of quantification were set to zero for analysis. PK parameters were determined from the time concentration profile using noncompartmental analysis.
Time frame: Parts 1, 2, 3, and 4: Cycles 1 and 2 pre-dose, 0.25, 3, 6, 24, 72, 168, 336, 504 (except Part 3) hours post-dose
Population: The PK analysis set included all participants who received at least one dose of bemarituzumab and had at least one PK sample collected. Participants with data available at each timepoint are presented.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: Bemarituzumab Dose 1 With Docetaxel | Maximum Observed Serum Concentration (Cmax) of Bemarituzumab | Cycle 1 | 599 mcg/mL |
| Part 1: Bemarituzumab Dose 1 With Docetaxel | Maximum Observed Serum Concentration (Cmax) of Bemarituzumab | Cycle 2 | 379 mcg/mL |
| Part 1: Bemarituzumab Dose 2 With Docetaxel | Maximum Observed Serum Concentration (Cmax) of Bemarituzumab | Cycle 1 | 746 mcg/mL |
| Part 1: Bemarituzumab Dose 2 With Docetaxel | Maximum Observed Serum Concentration (Cmax) of Bemarituzumab | Cycle 2 | 715 mcg/mL |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Maximum Observed Serum Concentration (Cmax) of Bemarituzumab | Cycle 1 | 646 mcg/mL |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Maximum Observed Serum Concentration (Cmax) of Bemarituzumab | Cycle 2 | 601 mcg/mL |
| Part 3: Bemarituzumab Dose 1 | Maximum Observed Serum Concentration (Cmax) of Bemarituzumab | Cycle 2 | 532 mcg/mL |
| Part 3: Bemarituzumab Dose 1 | Maximum Observed Serum Concentration (Cmax) of Bemarituzumab | Cycle 1 | 398 mcg/mL |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Maximum Observed Serum Concentration (Cmax) of Bemarituzumab | Cycle 1 | 561 mcg/mL |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Maximum Observed Serum Concentration (Cmax) of Bemarituzumab | Cycle 2 | 322 mcg/mL |
Secondary
Observed Concentration at the End of a Dose Interval (Ctrough) of Bemarituzumab
Bemarituzumab serum concentrations with values below the limit of quantification were set to zero for analysis. PK parameters were determined from the time concentration profile using noncompartmental analysis.
Time frame: Pre-dose Cycle 2 Day 1 and Cycle 3 day 1
Population: The PK analysis set included all participants who received at least one dose of bemarituzumab and had at least one PK sample collected. Participants with data available at each timepoint are presented.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: Bemarituzumab Dose 1 With Docetaxel | Observed Concentration at the End of a Dose Interval (Ctrough) of Bemarituzumab | Pre-dose Cycle 2 Day 1 | 51.5 mcg/mL |
| Part 1: Bemarituzumab Dose 1 With Docetaxel | Observed Concentration at the End of a Dose Interval (Ctrough) of Bemarituzumab | Pre-dose Cycle 3 Day 1 | 79.1 mcg/mL |
| Part 1: Bemarituzumab Dose 2 With Docetaxel | Observed Concentration at the End of a Dose Interval (Ctrough) of Bemarituzumab | Pre-dose Cycle 2 Day 1 | 93.7 mcg/mL |
| Part 1: Bemarituzumab Dose 2 With Docetaxel | Observed Concentration at the End of a Dose Interval (Ctrough) of Bemarituzumab | Pre-dose Cycle 3 Day 1 | 149 mcg/mL |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Observed Concentration at the End of a Dose Interval (Ctrough) of Bemarituzumab | Pre-dose Cycle 2 Day 1 | 88.9 mcg/mL |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Observed Concentration at the End of a Dose Interval (Ctrough) of Bemarituzumab | Pre-dose Cycle 3 Day 1 | 111 mcg/mL |
| Part 3: Bemarituzumab Dose 1 | Observed Concentration at the End of a Dose Interval (Ctrough) of Bemarituzumab | Pre-dose Cycle 3 Day 1 | 140 mcg/mL |
| Part 3: Bemarituzumab Dose 1 | Observed Concentration at the End of a Dose Interval (Ctrough) of Bemarituzumab | Pre-dose Cycle 2 Day 1 | 147 mcg/mL |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Observed Concentration at the End of a Dose Interval (Ctrough) of Bemarituzumab | Pre-dose Cycle 2 Day 1 | 29.9 mcg/mL |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Observed Concentration at the End of a Dose Interval (Ctrough) of Bemarituzumab | Pre-dose Cycle 3 Day 1 | 69.2 mcg/mL |
Secondary
Overall Survival (OS)
OS was defined as the time from the date of first dose of investigational product until event of death due to any cause through the analysis cutoff date. Participants still alive were censored at the date last known to be alive through the analysis cutoff date.
Time frame: Participants completed the LTFU for survival every 3 months ± 1 month after the safety follow-up visit (at 28 days after the last dose of bemarituzumab), up to the end of the study. Median time on study was approximately 21 weeks
Population: The safety analysis set included all participants who received at least one dose of bemarituzumab.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Bemarituzumab Dose 1 With Docetaxel | Overall Survival (OS) | 6.0 months |
| Part 1: Bemarituzumab Dose 2 With Docetaxel | Overall Survival (OS) | 12.8 months |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Overall Survival (OS) | NA months |
| Part 3: Bemarituzumab Dose 1 | Overall Survival (OS) | 5.4 months |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Overall Survival (OS) | NA months |
Secondary
Percentage of Participants Who Achieved an Objective Response (OR)
OR was defined as the best overall response of confirmed complete response (CR) or confirmed partial response (PR) as defined by the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). CR: disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to \<10 mm. All lymph nodes must have been non-pathological in size (\< 10 mm). PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Every 6 (+/- 1) weeks from the first dose of bemarituzumab (cycle 1 day 1) up to week 54, then every 12 (+/- 2 weeks), up to the end of the long term follow-up (LTFU) period (median time on study was approximately 21 weeks)
Population: The safety analysis set included all participants who received at least one dose of bemarituzumab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Bemarituzumab Dose 1 With Docetaxel | Percentage of Participants Who Achieved an Objective Response (OR) | 0.0 percentage of participants |
| Part 1: Bemarituzumab Dose 2 With Docetaxel | Percentage of Participants Who Achieved an Objective Response (OR) | 22.2 percentage of participants |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Percentage of Participants Who Achieved an Objective Response (OR) | 10.3 percentage of participants |
| Part 3: Bemarituzumab Dose 1 | Percentage of Participants Who Achieved an Objective Response (OR) | 0.0 percentage of participants |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Percentage of Participants Who Achieved an Objective Response (OR) | 25.0 percentage of participants |
Secondary
Progression-free Survival (PFS)
PFS was defined as the time from date of first dose of investigational product until the first documentation of radiologic disease progression or death due to any cause, whichever occurred first, in the absence of subsequent anticancer therapy. PFS was censored at the last evaluable post-baseline tumor assessment prior to subsequent anticancer therapy; otherwise, at first dose of investigational product. Progression was based on RECIST v1.1 criteria. PD: at least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an increase of at least 5 mm. Unequivocal progression of existing non-target lesions.
Time frame: Participants completed the LTFU for survival every 3 months ± 1 month after the safety follow-up visit (at 28 days after the last dose of bemarituzumab), up to the end of the study. Median time on study was approximately 21 weeks
Population: The safety analysis set included all participants who received at least one dose of bemarituzumab.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Bemarituzumab Dose 1 With Docetaxel | Progression-free Survival (PFS) | 4.2 months |
| Part 1: Bemarituzumab Dose 2 With Docetaxel | Progression-free Survival (PFS) | 4.2 months |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Progression-free Survival (PFS) | 4.0 months |
| Part 3: Bemarituzumab Dose 1 | Progression-free Survival (PFS) | 1.8 months |
| Part 4: Bemarituzumab Dose 2 First-line Combination Therapy | Progression-free Survival (PFS) | 5.6 months |