Cited 23 times in
Safety and Clinical Activity of a New Anti-PD-L1 Antibody as Monotherapy or Combined with Targeted Therapy in Advanced Solid Tumors: The PACT Phase Ia/Ib Trial
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 정현철 | - |
dc.date.accessioned | 2022-09-14T01:18:03Z | - |
dc.date.available | 2022-09-14T01:18:03Z | - |
dc.date.issued | 2021-03 | - |
dc.identifier.issn | 1078-0432 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/190381 | - |
dc.description.abstract | Purpose: This phase Ia/Ib PACT study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of a new programmed cell death ligand 1 (PD-L1) inhibitor, LY3300054, as monotherapy or in combination with ramucirumab, abemaciclib, or merestinib (a type II MET kinase inhibitor) in patients with advanced, refractory solid tumors (NCT02791334). Patients and methods: Patients were enrolled into cohorts of escalating LY3300054 dose (phase Ia) as monotherapy (N = 15) or combined with ramucirumab (N = 10), abemaciclib (N = 24), or merestinib (N = 12). The phase Ib dose expansion enrolled 8 patients with melanoma in the monotherapy arm and 12 patients with pancreatic cancer in the merestinib combination arm. Combination treatments were administered concurrently from day 1 of each cycle. A 14-day lead-in abemaciclib arm was also explored. Primary endpoints were dose-limiting toxicity (DLT) and safety. Results: Treatment-related adverse events included fatigue and nausea in the monotherapy arm (13% for each), hypothyroidism (30%) in the ramucirumab arm, diarrhea (54%) in the abemaciclib arm, and nausea (25%) in the merestinib arm. DLTs associated with hepatoxicity were observed in 3 of 4 patients in the abemaciclib lead-in cohorts. No DLTs or grade 3 or 4 hepatoxicity were reported in the concurrent abemaciclib arm. Pharmacokinetic characteristics were comparable with other PD-L1 inhibitors. One patient in each arm experienced a partial response per RECIST v1.1 lasting ≥7 months. Conclusions: LY3300054 was well tolerated without unexpected safety concerns when administered alone or concurrently with ramucirumab, abemaciclib, or merestinib. Lead-in abemaciclib before combining with LY3300054 was not feasible due to hepatotoxicity. Durable clinical benefits were seen in all regimens. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | American Association for Cancer Research | - |
dc.relation.isPartOf | CLINICAL CANCER RESEARCH | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Adult | - |
dc.subject.MESH | Aged | - |
dc.subject.MESH | Aged, 80 and over | - |
dc.subject.MESH | Aminopyridines / administration & dosage | - |
dc.subject.MESH | Antibodies, Monoclonal / therapeutic use* | - |
dc.subject.MESH | Antibodies, Monoclonal, Humanized / administration & dosage | - |
dc.subject.MESH | Antineoplastic Combined Chemotherapy Protocols / therapeutic use* | - |
dc.subject.MESH | B7-H1 Antigen / antagonists & inhibitors* | - |
dc.subject.MESH | B7-H1 Antigen / immunology | - |
dc.subject.MESH | Benzimidazoles / administration & dosage | - |
dc.subject.MESH | Drug Therapy, Combination | - |
dc.subject.MESH | Female | - |
dc.subject.MESH | Follow-Up Studies | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Indazoles / administration & dosage | - |
dc.subject.MESH | Male | - |
dc.subject.MESH | Maximum Tolerated Dose | - |
dc.subject.MESH | Middle Aged | - |
dc.subject.MESH | Neoplasms / drug therapy* | - |
dc.subject.MESH | Neoplasms / immunology | - |
dc.subject.MESH | Neoplasms / pathology | - |
dc.subject.MESH | Niacinamide / administration & dosage | - |
dc.subject.MESH | Niacinamide / analogs & derivatives | - |
dc.subject.MESH | Prognosis | - |
dc.title | Safety and Clinical Activity of a New Anti-PD-L1 Antibody as Monotherapy or Combined with Targeted Therapy in Advanced Solid Tumors: The PACT Phase Ia/Ib Trial | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | Amita Patnaik | - |
dc.contributor.googleauthor | Timothy A Yap | - |
dc.contributor.googleauthor | Hyun Cheol Chung | - |
dc.contributor.googleauthor | Maria J de Miguel | - |
dc.contributor.googleauthor | Yung-Jue Bang | - |
dc.contributor.googleauthor | Chia-Chi Lin | - |
dc.contributor.googleauthor | Wu-Chou Su | - |
dc.contributor.googleauthor | Antoine Italiano | - |
dc.contributor.googleauthor | Kay Hoong Chow | - |
dc.contributor.googleauthor | Anna M Szpurka | - |
dc.contributor.googleauthor | Danni Yu | - |
dc.contributor.googleauthor | Yumin Zhao | - |
dc.contributor.googleauthor | Michelle Carlsen | - |
dc.contributor.googleauthor | Shelly Schmidt | - |
dc.contributor.googleauthor | Burkhard Vangerow | - |
dc.contributor.googleauthor | Leena Gandhi | - |
dc.contributor.googleauthor | Xiaojian Xu | - |
dc.contributor.googleauthor | Johanna Bendell | - |
dc.identifier.doi | 10.1158/1078-0432.CCR-20-2821 | - |
dc.contributor.localId | A03773 | - |
dc.relation.journalcode | J00564 | - |
dc.identifier.pmid | 33229456 | - |
dc.identifier.url | https://aacrjournals.org/clincancerres/article/27/5/1267/83962/Safety-and-Clinical-Activity-of-a-New-Anti-PD-L1 | - |
dc.contributor.alternativeName | Chung, Hyun Cheol | - |
dc.contributor.affiliatedAuthor | 정현철 | - |
dc.citation.volume | 27 | - |
dc.citation.number | 5 | - |
dc.citation.startPage | 1267 | - |
dc.citation.endPage | 1277 | - |
dc.identifier.bibliographicCitation | CLINICAL CANCER RESEARCH, Vol.27(5) : 1267-1277, 2021-03 | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.