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

NCT05383482 | Completed Phase 1

• 1 other identifier: LAE202CN2101
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Solid Tumor; NSCLC; Cervical Cancer; Endometrial Cancer; Esophageal Cancer; Gastric and Gastroesophageal Junction Adenocarcinoma

Outcome Measures

Primary Outcomes (3)

• Phase I: Frequency and severity of Adverse Events (AEs),including incidence rate of DLTs

  Phase I: Findings on physical examination, ECG, vital signs, and reports of the laboratory results based on the CTCAE v5.0

  Through study completion for an average of 12 months

• Phase I: Recommended Phase II dose

  Phase I: Determining the RP2D of the Combination therapy for phase II

  about 12 months

• Phase II: Overall Response Rate (ORR) based on RECIST 1.1

  Anti-tumor activity of Afuresertib in combination with Sintilimab and Nab-paclitaxel or Docetaxel in EC/CC/ GC/GEJC/EsC/NSCLC

  Change from Baseline beginning at Cycle 3 Day 1 and then every 6 weeks × 18weeks then every 9 weeks through study completion, an average of 2 years (each cycle is 21 days)

Secondary Outcomes (7)

• Phase I：Overall Response Rate (ORR) based on RECIST 1.1

  Change from Baseline beginning at Cycle 3 Day 1 and then every 6 weeks × 18weeks then every 9 weeks through study completion, an average of 1 year (each cycle is 21 days)

• Disease Control Rate (DCR) based on RECIST 1.1

  Change from Baseline beginning at Cycle 3 Day 1 and then every 6 weeks × 18weeks then every 9 weeks through study completion, an average of 1 year (each cycle is 21 days)

• Duration of Response (DOR) based on RECIST 1.1

  Change from Baseline beginning at Cycle 3 Day 1 and then every 6 weeks × 18weeks then every 9 weeks through study completion, an average of 1 year (each cycle is 21 days)

• Progression Free Survival (PFS) based on RECIST 1.1

  Change from Baseline beginning at Cycle 3 Day 1 and then every 6 weeks × 18weeks then every 9 weeks through study completion, an average of 1 year (each cycle is 21 days)

• Assessing pharmacokinetics parameters

  Assessed on Day 1, Day 15 of Cycle 1 and Day1 of Cycle 3 (each cycle is 21 days)

Study Arms (2)

Afuresertib in combination with Sintilimab and Nab-paclitaxel

EXPERIMENTAL

Afuresertib in combination with Sintilimab and Nab-paclitaxel in patients with Endometrial Cancer and Cervical Cancer

Drug: Afuresertib; Drug: Nab paclitaxel; Drug: Sintilimab

Afuresertib in combination with Sintilimab and Docetaxel

EXPERIMENTAL

Afuresertib in combination with Sintilimab and Docetaxel in patients with Gastric and Gastroesophageal Junction Adenocarcinoma, Non-Small Cell Lung Cancer and Esophageal Cancer

Drug: Afuresertib; Drug: Docetaxel; Drug: Sintilimab

Interventions

Afuresertib DRUG

Afuresertib 125 mg PO on days 1-5, 8-12, 15-19 or Afuresertib 125 mg QD

Also known as: LAE002

Afuresertib in combination with Sintilimab and Docetaxel; Afuresertib in combination with Sintilimab and Nab-paclitaxel

Nab paclitaxel DRUG

Nab-paclitaxel 80 mg/M2 IV D1,8, Q3W or 100 mg/M2 IV D1,8, Q3W

Afuresertib in combination with Sintilimab and Nab-paclitaxel

Docetaxel DRUG

Docetaxel 50 mg/M2 IV D1 Q3W or Docetaxel 60 mg/M2 IV D1 Q3W

Afuresertib in combination with Sintilimab and Docetaxel

Sintilimab DRUG

Sintilimab 200 mg Q3W

Afuresertib in combination with Sintilimab and Docetaxel; Afuresertib in combination with Sintilimab and Nab-paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be \>=18 years of age on the day of signing the informed consent and be able to provide written informed consent for the trial.
• Prior treatments:
• In phase I, patients had at least 1 prior systemic anti-cancer treatment (including neoadjuvant/adjuvant therapy are qualified to be enrolled). Patients who resistant to anti-PD-1/PD-L1 are preferred.
• In phase II, patients should meet the following 2 criteria simultaneously:
• A: resistant to anti-PD-1/PD-L1: previously received at least 6 weeks （2 cycles） anti-PD-1/PD-L1 (including neoadjuvant/adjuvant therapy) and progressed after anti-PD-1/PD-L1 or their combination therapies.
• B: received \<=3 lines systematic therapy during recurrent/metastatic period.
• Tumor diagnosis:
• In phase I, patients had a histology confirmed diagnosis of locally advanced or metastatic solid tumors who had at least 1 prior systemic anti-cancer treatment including neoadjuvant/adjuvant therapy are qualified to be enrolled. The patients with the 5 selected cancer types below who resistant to prior anti-PD-1/PL-1 or its combination therapies will be enrolled with a higher priority.
• In phase II, the patients have only the following diagnoses will be allowed:
• CC: Patients with histologically confirmed metastatic, recurrent or persistent squamous cell carcinoma, adenosquamous carcinoma, adenocarcinoma of the cervix are allowed. The other histological types of cervical cancer will be excluded.
• EC: Patients with histologically confirmed metastatic, recurrent or persistent Epithelial Endometrial Carcinoma with endometrioid, high grade serous, or clear cell carcinoma. The other histological types of endometrial cancer will be excluded.
• EsC: Patients with histologically confirmed local advanced, recurrent or metastasis esophageal squamous cell carcinoma or Her2- adenocarcinoma.
• NSCLC: Patients with histologically confirmed locally advanced, recurrent, or metastatic Non-Small Cell Lung Cancer (squamous cell carcinoma or adenocarcinoma, adenosquamous carcinoma), who have EGFR wild type status, KRAS wild type status and ALK- negative rearrangement status.
• GC/GEJC: Patients with histologically confirmed locally advanced, recurrent, or metastatic Her2- gastric adenocarcinoma or gastroesophageal junction adenocarcinoma or squamous cell carcinoma allowed.
• Biomarker test:

You may not qualify if:

• Pregnancy or lactation. A woman of child-bearing potential, who has a positive urine pregnancy test prior to treatment. If the urine test is cannot be confirmed as negative, a serum pregnancy test will be required.
• Prior anti-cancer treatment or any investigational agent within 28 days (or 5 half-lives, whichever is shorter) prior to the first dose of study drugs.
• Patients that have previously received AKT or PI3 kinase pathway or mTOR inhibitors will not be enrolled.
• Patients that discontinued prior anti PD-1/PD-L1 due to immune related AE.
• Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
• With clinically uncontrolled pleural effusion/ascites (patients who do not need effusion drainage or have no significant increase in effusion 3 days after stopping drainage can be enrolled);
• With a tumor compressing the surrounding important organs, compressing the superior vena cava, or invading the mediastinal great vessels, heart, etc.;
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, transitional cell carcinoma of urothelial cancer, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• History of seizure of condition that may predispose to seizure that needs anti-epileptic medications; brain arteriovenous malformation; or intracranial masses, such as schwannomas and meningiomas that are causing edema or mass effect.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• Has severe hypersensitivity (≥Grade 3) to Sintilimab or afuresertib and/or any of their excipients.
• Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs) prior to the first dose of study treatment. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
• Has a history of (non-infectious) pneumonitis that required steroids or has concurrent interstitial pneumonia.

Sponsors & Collaborators

• Laekna Limited: lead

Study Sites (5)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Chongqing Cancer Hospital

Chongqing, Chengdu, China

Location

Jilin Cancer Hospital

Changchun, Jilin, China

Location

Zhongshan Hospital, Fudan University

Shanghai, Shanghai Municipality, China

Location

West China Second University Hosital, Sichuan University

Chengdu, Sichuan, China

Location

MeSH Terms

Conditions

Uterine Cervical Neoplasms; Endometrial Neoplasms; Esophageal Neoplasms

Interventions

afuresertib; Taxes; Docetaxel; sintilimab

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Economics; Health Care Economics and Organizations; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Lin Shen, Director

  Beijing Cancer Hospital, China

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2022
• First Posted: May 20, 2022
• Study Start: July 1, 2022
• Primary Completion: June 25, 2024
• Study Completion: July 18, 2024
• Last Updated: November 17, 2025

Record last verified: 2025-11

Locations

CN (5)