Phase 1 N=65 Treatment

Study to Evaluate GSK3052230 in Combination With Paclitaxel and Carboplatin, or Docetaxel or as Single Agent in Subjects With Solid Malignancies and Deregulated Fibroblast Growth Factor (FGF) Pathway Signaling

Neoplasms

Bottom Line

View on ClinicalTrials.gov: NCT01868022 ↗

Enrolled (actual)

Serious AEs

35.4%

Results posted

Feb 2019

Primary outcome: Primary: Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs) — 3; 3; 14; 3 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 1
Interventions: GSK3052230 (Drug); paclitaxel (Drug); carboplatin (Drug); docetaxel (Drug); pemetrexed (Drug); cisplatin (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: GlaxoSmithKline
Primary completion: Oct 2017

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs)	3; 3; 14; 3; 3; 3	—
PRIMARY Number of Participants With Severe AEs and SAEs	0; 0; 0; 0; 0; 0	—
PRIMARY Number of Participants Withdrew Due to AEs	0; 0; 0; 0; 1; 0	—
PRIMARY Number of Participants With Dose Reduction	1; 0; 3; 1; 0; 2	—
PRIMARY Number of Participants With Dose Delays	0; 2; 4; 2; 1; 0	—
PRIMARY Treatment Duration With GSK3052230	7.0; 15.0; 8.0; 6.0; 4.0; 6.0	—
PRIMARY Number of Participants With Dose-Limiting Toxicities (DLT)	0; 0; 0; 0; 0; 0	—
PRIMARY Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)	6.3; 0.5; 2.0; -0.6; 6.0; 3.5	—
PRIMARY Change From Baseline in Heart Rate	-0.3; 3.2; 8.0; 28.0; 10.5; 0.6	—
PRIMARY Change From Baseline in Temperature	-0.30; -0.38; 0.35; 0.10; 1.03; -0.03	—
PRIMARY Number of Participants With Clinically Significant Findings for 12-lead Electrocardiogram (ECG)	0; 2; 8; 2; 2; 3	—
PRIMARY Number of Participants With Abnormal Echocardiogram (ECHO) Findings	0; 1; 0; 1; 2; 2	—
PRIMARY Number of Participants With Clinical Chemistry Changes From Baseline With Respect to the Normal Range	0; 0; 0; 0; 0; 1	—
PRIMARY Number of Participants With the Abnormal Urinalysis Findings	0; 0; 1; 0; 0; 0	—
PRIMARY Number of Participants With Hematology Change From Baseline With Respect to the Normal Range	0; 0; 1; 0; 1; 0	—
PRIMARY Number of Participants With Maximum Tolerated Dose (MTD) or Maximum Feasible Dose (MFD)	14; 3; 25	—
PRIMARY Number of Participants With Best Response	0; 0; 0; 0; 0; 0	—
PRIMARY Number of Participants With Overall Response Rate (ORR)	1; 2; 6; 0; 0; 0	—
SECONDARY Progression Free Survival (PFS) as Assessed by Investigator	4.1; NA; 5.5; 4.6; 9.5; 5.1	—
SECONDARY Clearance of GSK3052230	—	—
SECONDARY Volume of Distribution of GSK3052230	—	—
SECONDARY Number of Participants With Relevant Covariates That Influence Exposure of GSK3052230	—	—
SECONDARY Change From Baseline in Forced Vital Capacity (FVC) in of Arm C Participants With Malignant Pleural Mesothelioma (MPM)	0.303; 0.280; 0.138; -0.340; 0.413; 0.600	—

Summary

This phase IB trial aims to identify anticancer activity of GSK3052230 in subjects with malignancies with abnormal dependence on FGF pathway signaling. Combination doses of GSK3052230 with standard of care chemotherapy in the first and second line or greater setting of metastatic squamous non-small cell lung cancer (NSCLC) and first line malignant pleural mesothelioma subjects will be studied in the 3+3 dose-escalation design. This will be a multi-arm, multicenter, non-randomized, parallel-group, uncontrolled, open-label Phase IB study designed to evaluate the safety, tolerability and preliminary activity of GSK3052230 in combination with paclitaxel + carboplatin (Arm A), in combination with docetaxel (Arm B), or in combination with pemetrexed + cisplatin (Arm C). Approximately 70 subjects will be enrolled in the study (approximately up to 120 may be enrolled).

Eligibility Criteria

Inclusion Criteria

Signed written informed consent
Histologically or cytologically confirmed diagnosis: Arm A and B- stage IV recurrent metastatic squamous NSCLC with Fibroblast growth factor receptor 1 (FGFR1) gene amplification by central laboratory testing. Arm C- recurrent after local therapy or unresectable MPM with measurable lesions.

For specific arms the following requirements:

Arm A: Subjects who have received no prior therapy for Stage IIIB or Stage IV or recurrent metastatic disease. Note, to avoid any undue delay of initiating systemic chemotherapy for these subjects with newly diagnosed metastatic disease, it is allowed to initiate the first cycle of chemotherapy while eligibility for the study is still being determined, as long as the first dose of GSK3052230 is given no later than Cycle 2 Day 1 of chemotherapy. In addition, subjects with Stage IIIB or Stage IV disease and recurrence after previous NSCLC that has been treated with surgery and adjuvant chemotherapy or a radio- chemotherapy regimen with curative intent are eligible, provided 6 months has passed since this treatment ended.

Arm B: Subjects who have documented tumor progression (based on radiological imaging) or intolerability after receiving at least one prior line of platinum containing combination chemotherapy for Stage IIIB or Stage IV or recurrent metastatic disease. Note: Prior treatment should not include docetaxel but may have included paclitaxel.

Arm C: Subjects who have received no prior systemic therapy for MPM.

Availability of archival tumor tissue required for assessment of deregulated FGF pathway signalling, but not limited to, FGFR1 amplification or FGF2 or FGFR1 expression. If archival tissue is not available, a fresh biopsy is required. In Arms A and B, subjects will be prospectively screened for FGFR1 gene amplification using a Fluorescence in situ hybridization (FISH) assay for the dose expansion and the MTD/MFD cohorts only. For inclusion in this study, based on the central laboratory testing, FGFR1 gene amplification must meet one of the following criteria: a ratio of FGFR1/CEN 8 of >=2; or average number of FGFR1 signals per tumor nucleus of >=6; or the percentage of tumor nuclei containing >=5 FGFR1 signals is >=50%.

In Arm C, FGF2 expression by IHC will be evaluated retrospectively in tissue samples by a central laboratory and is not a requirement for study entry.

Measurable disease per RECIST version 1.1 (Arm A and B) and modified RECIST for Arm C.
Male or female >=18 years of age.
Women of childbearing potential must have a negative serum pregnancy test within 7 days of first dose of study treatment and agree to use effective contraception, from 14 days prior to the first dose of study treatment, throughout the study, and for 6 months following the last dose of chemotherapy or 4 weeks after the last dose of GSK3052230, whichever is latest. .
Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception for at least 2 weeks prior to administration of the first dose of study treatment and for at least 6 months after the last dose of chemotherapy to allow for clearance of any altered sperm.
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 for Arm A and C subjects and 0-2 for Arm B.
French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category
Must have adequate organ function as defined by the following baseline values: Absolute neutrophil count >=1.5 x 10^9/Liter, Hemoglobin >=9 gram (g)/decilitre(dL), Platelets >=100 x 10^9/L, Partial thromboplastin time (PTT) =2.5 g/dL, Serum total bilirubin =45 mL/min (Arm A or B), >=65 mL/min (Arm C), Left ventricular ejection fraction >=50% by ECHO.

Exclusion Criteria

For Arms A and C: Treatment with any FGFR inhibitor. For Arm B: Treatment with any anti-cancer therapy (for bi

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01868022). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.