Safety, Tolerability, and Pharmacokinetics of Senaparib, a Novel PARP1/2 Inhibitor, in Chinese Patients With Advanced Solid Tumors : A Phase I Trial
© The Author(s) 2023. Published by Oxford University Press..
BACKGROUND: Senaparib, a novel poly(ADP-ribose) polymerase 1/2 inhibitor, demonstrated antitumor activity in preclinical studies. This phase I, first-in-human, dose-escalation/-expansion study explored the pharmacokinetics, safety and tolerability, and preliminary antitumor activity of senaparib in Chinese patients with advanced solid tumors.
PATIENTS AND METHODS: Adults with advanced solid tumors who had failed ³1 line of prior systemic treatment were enrolled. Senaparib (once daily [QD]) dose was escalated from 2 mg until the maximum tolerated dose (MTD)/recommended phase II dose (RP2D) using a modified 3 + 3 design. Dose expansion included: dose groups with ≥1 objective response and one dose higher, as well as those at the MTD/RP2D. Primary objectives were to evaluate the safety and tolerability, and determine the MTD and/or RP2D of senaparib.
RESULTS: Fifty-seven patients were enrolled across 10 dose groups (2-120 mg QD, and 50 mg twice daily). No dose-limiting toxicities were observed. The most common senaparib-related adverse events were anemia (80.9%), white blood cell count decreased (43.9%), platelet count decreased (28.1%), and asthenia (26.3%). Senaparib exposure increased dose proportionately at 2-80 mg; absorption saturated at 80-120 mg. Senaparib accumulation was minimal after repeated QD administration (accumulation ratio=1.1-1.5). The objective response rate was 22.7% (n=10/44) overall (all partial responses) and 26.9% (n=7/26) for patients harboring BRCA1/BRCA2 mutations. Disease control rates were 63.6% and 73.1%, respectively.
CONCLUSIONS: Senaparib was well tolerated and demonstrated promising antitumor activity in Chinese patients with advanced solid tumors. The RP2D for this clinical study in China was identified as 100 mg QD.
CLINICALTRIALS.GOV IDENTIFIER: NCT03508011.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:28 |
|---|---|
| Enthalten in: |
The oncologist - 28(2023), 12 vom: 11. Dez., Seite e1259-e1267 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Cao, Junning [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 16.12.2023 Date Revised 26.12.2023 published: Print ClinicalTrials.gov: NCT03508011 Citation Status MEDLINE |
|---|
| doi: |
10.1093/oncolo/oyad163 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM358396794 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM358396794 | ||
| 003 | DE-627 | ||
| 005 | 20231227141250.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1093/oncolo/oyad163 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1239.xml |
| 035 | |a (DE-627)NLM358396794 | ||
| 035 | |a (NLM)37338150 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Cao, Junning |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Safety, Tolerability, and Pharmacokinetics of Senaparib, a Novel PARP1/2 Inhibitor, in Chinese Patients With Advanced Solid Tumors |b A Phase I Trial |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 16.12.2023 | ||
| 500 | |a Date Revised 26.12.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a ClinicalTrials.gov: NCT03508011 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2023. Published by Oxford University Press. | ||
| 520 | |a BACKGROUND: Senaparib, a novel poly(ADP-ribose) polymerase 1/2 inhibitor, demonstrated antitumor activity in preclinical studies. This phase I, first-in-human, dose-escalation/-expansion study explored the pharmacokinetics, safety and tolerability, and preliminary antitumor activity of senaparib in Chinese patients with advanced solid tumors | ||
| 520 | |a PATIENTS AND METHODS: Adults with advanced solid tumors who had failed ³1 line of prior systemic treatment were enrolled. Senaparib (once daily [QD]) dose was escalated from 2 mg until the maximum tolerated dose (MTD)/recommended phase II dose (RP2D) using a modified 3 + 3 design. Dose expansion included: dose groups with ≥1 objective response and one dose higher, as well as those at the MTD/RP2D. Primary objectives were to evaluate the safety and tolerability, and determine the MTD and/or RP2D of senaparib | ||
| 520 | |a RESULTS: Fifty-seven patients were enrolled across 10 dose groups (2-120 mg QD, and 50 mg twice daily). No dose-limiting toxicities were observed. The most common senaparib-related adverse events were anemia (80.9%), white blood cell count decreased (43.9%), platelet count decreased (28.1%), and asthenia (26.3%). Senaparib exposure increased dose proportionately at 2-80 mg; absorption saturated at 80-120 mg. Senaparib accumulation was minimal after repeated QD administration (accumulation ratio=1.1-1.5). The objective response rate was 22.7% (n=10/44) overall (all partial responses) and 26.9% (n=7/26) for patients harboring BRCA1/BRCA2 mutations. Disease control rates were 63.6% and 73.1%, respectively | ||
| 520 | |a CONCLUSIONS: Senaparib was well tolerated and demonstrated promising antitumor activity in Chinese patients with advanced solid tumors. The RP2D for this clinical study in China was identified as 100 mg QD | ||
| 520 | |a CLINICALTRIALS.GOV IDENTIFIER: NCT03508011 | ||
| 650 | 4 | |a Clinical Trial, Phase I | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a BRCA mutation | |
| 650 | 4 | |a PARP inhibitor | |
| 650 | 4 | |a phase I study | |
| 650 | 4 | |a senaparib | |
| 650 | 4 | |a solid tumors | |
| 650 | 4 | |a synthetic lethality | |
| 650 | 7 | |a Poly(ADP-ribose) Polymerase Inhibitors |2 NLM | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a PARP1 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.4.2.30 |2 NLM | |
| 650 | 7 | |a Poly (ADP-Ribose) Polymerase-1 |2 NLM | |
| 650 | 7 | |a EC 2.4.2.30 |2 NLM | |
| 700 | 1 | |a Guo, Hongqian |e verfasserin |4 aut | |
| 700 | 1 | |a Ji, Dongmei |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Weina |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Shun |e verfasserin |4 aut | |
| 700 | 1 | |a Hsieh, Chih-Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Xiong Cai, Sui |e verfasserin |4 aut | |
| 700 | 1 | |a Edward Tian, Ye |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Cong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Pin |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Binghe |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The oncologist |d 1998 |g 28(2023), 12 vom: 11. Dez., Seite e1259-e1267 |w (DE-627)NLM095483306 |x 1549-490X |7 nnns |
| 773 | 1 | 8 | |g volume:28 |g year:2023 |g number:12 |g day:11 |g month:12 |g pages:e1259-e1267 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1093/oncolo/oyad163 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 28 |j 2023 |e 12 |b 11 |c 12 |h e1259-e1267 | ||