An open-label phase IB study to evaluate GSK3052230 in combination with paclitaxel and carboplatin, or docetaxel, in FGFR1-amplified non-small cell lung cancer

Daniel Morgensztern, Nina Karaseva, Enriqueta Felip, Ignacio Delgado, Olga Burdaeva, Manuel Dómine, Primo N Lara, Paul K. Paik, Ulrik Lassen, Sergey Orlov, José Trigo, Marina Shomova, Katherine Baker-Neblett, James Vasquez, Xiaowei Wang, Li Yan, Ionel Mitrica, M. Phillip DeYoung, Pilar Garrido

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Objectives: GSK3052230 (FP-1039) is a soluble fusion protein that acts as ligand trap sequestering fibroblast growth factors (FGFs) involved in tumor growth and angiogenesis, while sparing the hormonal FGFs. Because of this selectivity, the molecule is predicted to avoid toxicities associated with small molecule inhibitors of FGFR, including hyperphosphatemia and retinal, nail, and skin toxicities. Herein we report the results of a phase 1b study where GSK3052330 was administered with standard of care chemotherapy in FGFR1-amplified squamous non-small cell lung cancer (sqNSCLC) patients. Methods and Methods: Eligible patients with stage IV or recurrent metastatic sqNSCLC harboring FGFR1 gene amplification received escalating doses of GSK3052230 in combination with paclitaxel and carboplatin at the starting doses 200 mg/m2 and AUC of 6, respectively, in the first line setting (Arm A) or docetaxel 75 mg/m2 in second line (Arm B). The primary endpoints of the study were safety and tolerability, to identify a maximum tolerated dose (MTD), and to assess overall response rate (ORR) based on investigator assessment. Results: Twenty-nine patients were enrolled into the study, including 20 patients on Arm A and 9 patients on Arm B. There were no dose limiting toxicities in either Arm and the MTD was not reached. The most common adverse events (AEs) were compatible with the chemotherapy backbone used in each Arm, including neutropenia, alopecia, nausea, arthralgia, asthenia, diarrhea and peripheral neuropathy. The overall response rate and median progression-free survival were 47% and 5.5 months, respectively, for Arm A and 0% and 4.6 months, respectively, for Arm B. Conclusion: GSK3052230 is a novel FGFR pathway inhibitor, which is well tolerated in combination with chemotherapy. Importantly, AEs associated with small molecule inhibitors of FGFR were not observed, as predicted by the unique mechanism of action of this drug.

Original languageEnglish (US)
Pages (from-to)74-79
Number of pages6
JournalLung Cancer
Volume136
DOIs
StatePublished - Oct 1 2019

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docetaxel
Carboplatin
Paclitaxel
Non-Small Cell Lung Carcinoma
Maximum Tolerated Dose
Fibroblast Growth Factors
Hyperphosphatemia
Asthenia
Drug Therapy
Gene Amplification
Alopecia
Arthralgia
Peripheral Nervous System Diseases
Standard of Care
Nails
Combination Drug Therapy
Neutropenia
Nausea
Disease-Free Survival
Area Under Curve

Keywords

  • Combination therapy
  • FGFR1
  • Ligand trap
  • Phase 1
  • Squamous non-small cell lung cancer

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

An open-label phase IB study to evaluate GSK3052230 in combination with paclitaxel and carboplatin, or docetaxel, in FGFR1-amplified non-small cell lung cancer. / Morgensztern, Daniel; Karaseva, Nina; Felip, Enriqueta; Delgado, Ignacio; Burdaeva, Olga; Dómine, Manuel; Lara, Primo N; Paik, Paul K.; Lassen, Ulrik; Orlov, Sergey; Trigo, José; Shomova, Marina; Baker-Neblett, Katherine; Vasquez, James; Wang, Xiaowei; Yan, Li; Mitrica, Ionel; DeYoung, M. Phillip; Garrido, Pilar.

In: Lung Cancer, Vol. 136, 01.10.2019, p. 74-79.

Research output: Contribution to journalArticle

Morgensztern, D, Karaseva, N, Felip, E, Delgado, I, Burdaeva, O, Dómine, M, Lara, PN, Paik, PK, Lassen, U, Orlov, S, Trigo, J, Shomova, M, Baker-Neblett, K, Vasquez, J, Wang, X, Yan, L, Mitrica, I, DeYoung, MP & Garrido, P 2019, 'An open-label phase IB study to evaluate GSK3052230 in combination with paclitaxel and carboplatin, or docetaxel, in FGFR1-amplified non-small cell lung cancer', Lung Cancer, vol. 136, pp. 74-79. https://doi.org/10.1016/j.lungcan.2019.08.011
Morgensztern, Daniel ; Karaseva, Nina ; Felip, Enriqueta ; Delgado, Ignacio ; Burdaeva, Olga ; Dómine, Manuel ; Lara, Primo N ; Paik, Paul K. ; Lassen, Ulrik ; Orlov, Sergey ; Trigo, José ; Shomova, Marina ; Baker-Neblett, Katherine ; Vasquez, James ; Wang, Xiaowei ; Yan, Li ; Mitrica, Ionel ; DeYoung, M. Phillip ; Garrido, Pilar. / An open-label phase IB study to evaluate GSK3052230 in combination with paclitaxel and carboplatin, or docetaxel, in FGFR1-amplified non-small cell lung cancer. In: Lung Cancer. 2019 ; Vol. 136. pp. 74-79.
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abstract = "Objectives: GSK3052230 (FP-1039) is a soluble fusion protein that acts as ligand trap sequestering fibroblast growth factors (FGFs) involved in tumor growth and angiogenesis, while sparing the hormonal FGFs. Because of this selectivity, the molecule is predicted to avoid toxicities associated with small molecule inhibitors of FGFR, including hyperphosphatemia and retinal, nail, and skin toxicities. Herein we report the results of a phase 1b study where GSK3052330 was administered with standard of care chemotherapy in FGFR1-amplified squamous non-small cell lung cancer (sqNSCLC) patients. Methods and Methods: Eligible patients with stage IV or recurrent metastatic sqNSCLC harboring FGFR1 gene amplification received escalating doses of GSK3052230 in combination with paclitaxel and carboplatin at the starting doses 200 mg/m2 and AUC of 6, respectively, in the first line setting (Arm A) or docetaxel 75 mg/m2 in second line (Arm B). The primary endpoints of the study were safety and tolerability, to identify a maximum tolerated dose (MTD), and to assess overall response rate (ORR) based on investigator assessment. Results: Twenty-nine patients were enrolled into the study, including 20 patients on Arm A and 9 patients on Arm B. There were no dose limiting toxicities in either Arm and the MTD was not reached. The most common adverse events (AEs) were compatible with the chemotherapy backbone used in each Arm, including neutropenia, alopecia, nausea, arthralgia, asthenia, diarrhea and peripheral neuropathy. The overall response rate and median progression-free survival were 47{\%} and 5.5 months, respectively, for Arm A and 0{\%} and 4.6 months, respectively, for Arm B. Conclusion: GSK3052230 is a novel FGFR pathway inhibitor, which is well tolerated in combination with chemotherapy. Importantly, AEs associated with small molecule inhibitors of FGFR were not observed, as predicted by the unique mechanism of action of this drug.",
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T1 - An open-label phase IB study to evaluate GSK3052230 in combination with paclitaxel and carboplatin, or docetaxel, in FGFR1-amplified non-small cell lung cancer

AU - Morgensztern, Daniel

AU - Karaseva, Nina

AU - Felip, Enriqueta

AU - Delgado, Ignacio

AU - Burdaeva, Olga

AU - Dómine, Manuel

AU - Lara, Primo N

AU - Paik, Paul K.

AU - Lassen, Ulrik

AU - Orlov, Sergey

AU - Trigo, José

AU - Shomova, Marina

AU - Baker-Neblett, Katherine

AU - Vasquez, James

AU - Wang, Xiaowei

AU - Yan, Li

AU - Mitrica, Ionel

AU - DeYoung, M. Phillip

AU - Garrido, Pilar

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Objectives: GSK3052230 (FP-1039) is a soluble fusion protein that acts as ligand trap sequestering fibroblast growth factors (FGFs) involved in tumor growth and angiogenesis, while sparing the hormonal FGFs. Because of this selectivity, the molecule is predicted to avoid toxicities associated with small molecule inhibitors of FGFR, including hyperphosphatemia and retinal, nail, and skin toxicities. Herein we report the results of a phase 1b study where GSK3052330 was administered with standard of care chemotherapy in FGFR1-amplified squamous non-small cell lung cancer (sqNSCLC) patients. Methods and Methods: Eligible patients with stage IV or recurrent metastatic sqNSCLC harboring FGFR1 gene amplification received escalating doses of GSK3052230 in combination with paclitaxel and carboplatin at the starting doses 200 mg/m2 and AUC of 6, respectively, in the first line setting (Arm A) or docetaxel 75 mg/m2 in second line (Arm B). The primary endpoints of the study were safety and tolerability, to identify a maximum tolerated dose (MTD), and to assess overall response rate (ORR) based on investigator assessment. Results: Twenty-nine patients were enrolled into the study, including 20 patients on Arm A and 9 patients on Arm B. There were no dose limiting toxicities in either Arm and the MTD was not reached. The most common adverse events (AEs) were compatible with the chemotherapy backbone used in each Arm, including neutropenia, alopecia, nausea, arthralgia, asthenia, diarrhea and peripheral neuropathy. The overall response rate and median progression-free survival were 47% and 5.5 months, respectively, for Arm A and 0% and 4.6 months, respectively, for Arm B. Conclusion: GSK3052230 is a novel FGFR pathway inhibitor, which is well tolerated in combination with chemotherapy. Importantly, AEs associated with small molecule inhibitors of FGFR were not observed, as predicted by the unique mechanism of action of this drug.

AB - Objectives: GSK3052230 (FP-1039) is a soluble fusion protein that acts as ligand trap sequestering fibroblast growth factors (FGFs) involved in tumor growth and angiogenesis, while sparing the hormonal FGFs. Because of this selectivity, the molecule is predicted to avoid toxicities associated with small molecule inhibitors of FGFR, including hyperphosphatemia and retinal, nail, and skin toxicities. Herein we report the results of a phase 1b study where GSK3052330 was administered with standard of care chemotherapy in FGFR1-amplified squamous non-small cell lung cancer (sqNSCLC) patients. Methods and Methods: Eligible patients with stage IV or recurrent metastatic sqNSCLC harboring FGFR1 gene amplification received escalating doses of GSK3052230 in combination with paclitaxel and carboplatin at the starting doses 200 mg/m2 and AUC of 6, respectively, in the first line setting (Arm A) or docetaxel 75 mg/m2 in second line (Arm B). The primary endpoints of the study were safety and tolerability, to identify a maximum tolerated dose (MTD), and to assess overall response rate (ORR) based on investigator assessment. Results: Twenty-nine patients were enrolled into the study, including 20 patients on Arm A and 9 patients on Arm B. There were no dose limiting toxicities in either Arm and the MTD was not reached. The most common adverse events (AEs) were compatible with the chemotherapy backbone used in each Arm, including neutropenia, alopecia, nausea, arthralgia, asthenia, diarrhea and peripheral neuropathy. The overall response rate and median progression-free survival were 47% and 5.5 months, respectively, for Arm A and 0% and 4.6 months, respectively, for Arm B. Conclusion: GSK3052230 is a novel FGFR pathway inhibitor, which is well tolerated in combination with chemotherapy. Importantly, AEs associated with small molecule inhibitors of FGFR were not observed, as predicted by the unique mechanism of action of this drug.

KW - Combination therapy

KW - FGFR1

KW - Ligand trap

KW - Phase 1

KW - Squamous non-small cell lung cancer

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