Trials / Completed

CompletedNCT05383482

Afuresertib +Sintilimab+Chemotherapy in Patients With Selected Solid Tumors That Resistance to Prior Anti-PD-1/PD-L1

A Phase I/II Dose-Escalation and Efficacy/Safety Study of Afuresertib Plus Sintilimab Plus Chemotherapy in Patients With Selected Solid Tumors That Resistance to Prior Anti-PD-1/PD-L1 Treatment

Status: Completed
Phase: Phase 1 / Phase 2
Study type: Interventional
Enrollment: 22 (actual)

Sponsor: Laekna Limited · Industry
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

Detailed description

This is a multicenter, open-label, dose-escalation and efficacy/safety Phase I/II study to assess RP2D, safety, tolerability and anti-tumor activity of Sintilimab + afuresertib + nab-paclitaxel or docetaxel administered as a combination therapy. This study is designed to identify the MTD and recommended Phase II dose (RP2D) of afuresertib in combination with sintilimab and nab-paclitaxel or docetaxel, respectively, to characterize the PK profile of afuresertib in phase I and to evaluate clinical efficacy and safety of the combination therapy in phase II. The study population in phase II is the patients with one of the five selected cancers who resistant to the prior anti-PD-1/PL-1 treatments (as a monotherapy or in combination with other anti-cancer drugs including chemotherapy) , such as EC, GC/GEJC, EsC, CC, and NSCLC. For phase I, the MTD is defined as the combination dose level with a DLT rate that is closest to the target toxicity rate (0.3). Patients in each dose level are planned to be enrolled in each cohort of size 3 and maximum to 9. Totally there would be no more than 42 cases in 2 combination groups (maximum 21 patients for each combination group). RP2D evaluation will be based on the observed safety profiles,PK ，PK was analyzed on 3-9 patients per dose of albumin-paclitaxel and docetaxel (pk Sample collection may be less than 3 if the group was discontinued due to DLT observed) . The dose escalation decision will be made based on the observed safety profiles of the tested combined doses and reviewed by the safety committee. The recommended combined dose level will be as follows based on BOIN dose escalation design. Once the RP2D of Sintilimab + afuresertib + nab-paclitaxel or docetaxel has been established, a cohort consisting of 50-125 patients with stratifying for each cancer type (10 -25 patients for each cancer type) who resistant to anti-PD-1/PD-L1 or its combination therapy (except for CC and EC, who did not receive prior anti-PD-1/PD-L1 could be enrolled. The preliminary anti-tumor efficacy of Sintilimab + afuresertib + nab-paclitaxel or docetaxel therapy will be assessed by the measurement of ORR, PFS, OS, DOR, DCR based on the tumor assessment in each of the five solid tumors. Patients with biomarkers, such as PTEN/PI3K/AKT alternations, will be analysed retrospectively as the subpopulations for their anti-tumor efficacy in each cancer type.

Conditions

Interventions

Type	Name	Description
DRUG	Afuresertib	Afuresertib 125 mg PO on days 1-5, 8-12, 15-19 or Afuresertib 125 mg QD
DRUG	Nab paclitaxel	Nab-paclitaxel 80 mg/M2 IV D1,8, Q3W or 100 mg/M2 IV D1,8, Q3W
DRUG	Docetaxel	Docetaxel 50 mg/M2 IV D1 Q3W or Docetaxel 60 mg/M2 IV D1 Q3W
DRUG	Sintilimab	Sintilimab 200 mg Q3W

Timeline

Start date: 2022-07-01
Primary completion: 2024-06-25
Completion: 2024-07-18
First posted: 2022-05-20
Last updated: 2025-11-17

Locations

5 sites across 1 country: China

Source: ClinicalTrials.gov record NCT05383482. Inclusion in this directory is not an endorsement.