Dataset Information

AZD8186 in Combination With Paclitaxel in Patients With Advanced Gastric Cancer: Results From a Phase Ib/II Study (KCSG ST18-20).

ABSTRACT:

Background

Loss of PTEN function leads to increased PI3Kβ signaling. AZD8186, a selective PI3Kβ/δ inhibitor, has shown anti-tumor activity in PTEN-deficient preclinical models. Although the combination of AZD8186 and paclitaxel was well tolerated, limited clinical efficacy was observed in advanced gastric cancer with PTEN loss.

Methods

In the phase Ib dose-escalation, subjects with advanced solid tumors received oral AZD8186 (60 mg or 120 mg; twice daily (BID); 5 days on/2 days off) plus intravenous paclitaxel (70 mg/m2 or 80 mg/m2; days 1, 8, and 15) every 4 weeks. In the phase II part, MRGC patients with PTEN loss or PTEN/PIK3CB gene abnormality were enrolled and received recommended phase II dose (RP2D) of AZD8186 plus paclitaxel. Primary endpoints were to determine maximum tolerated dose (MTD) and RP2D in phase Ib and 4-month progression-free survival (PFS) rate in phase II.

Results

In phase Ib, both MTD and RP2D were determined at paclitaxel 80 mg/m2 and AZD8186 120 mg BID. In phase II, 18 patients were enrolled [PTEN loss (n = 18) and PIK3CB mutation (n = 1)]. The 4-month PFS rate was 18.8% (3 of 16 evaluable patients) and further enrollment stopped due to futility.

Conclusion

Although the combination of AZD8186 and paclitaxel was well tolerated, limited clinical efficacy was observed.ClinicalTrials.gov Identifier: NCT04001569.

SUBMITTER: Suh KJ

PROVIDER: S-EPMC10485284 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

AZD8186 in Combination With Paclitaxel in Patients With Advanced Gastric Cancer: Results From a Phase Ib/II Study (KCSG ST18-20).

Suh Koung Jin KJ Ryu Min-Hee MH Zang Dae Young DY Bae Woo Kyun WK Lee Hye Seung HS Oh Hyeon Jeong HJ Kang Minsu M Kim Ji-Won JW Kim Bum Jun BJ Mortimer Peter G S PGS Kim Hee Jung HJ Lee Keun-Wook KW

The oncologist 20230901 9

<h4>Background</h4>Loss of PTEN function leads to increased PI3Kβ signaling. AZD8186, a selective PI3Kβ/δ inhibitor, has shown anti-tumor activity in PTEN-deficient preclinical models. Although the combination of AZD8186 and paclitaxel was well tolerated, limited clinical efficacy was observed in advanced gastric cancer with PTEN loss.<h4>Methods</h4>In the phase Ib dose-escalation, subjects with advanced solid tumors received oral AZD8186 (60 mg or 120 mg; twice daily (BID); 5 days on/2 days of ...[more]

PMID: 37036671

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Dataset Information

AZD8186 in Combination With Paclitaxel in Patients With Advanced Gastric Cancer: Results From a Phase Ib/II Study (KCSG ST18-20).

Background

Methods

Results

Conclusion

Publications

AZD8186 in Combination With Paclitaxel in Patients With Advanced Gastric Cancer: Results From a Phase Ib/II Study (KCSG ST18-20).

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