Solid TumorPhase 1/2NCT05383482
Afuresertib +Sintilimab+Chemotherapy in Patients With Selected Solid Tumors That Resistance to Prior Anti-PD-1/PD-L1
A Phase 1/2 study testing Afuresertib, Nab paclitaxel and Docetaxel in people with Solid Tumor and NSCLC, run by Laekna Limited at 5 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor, NSCLC, Cervical Cancer
- What is being tested?
- Afuresertib, Nab paclitaxel and Docetaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 5 sitesChina
- Study dates
- 1 Jul 2022to 18 Jul 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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:
- In phase I, the biomarker test with tumor sample is optional. However, blood test of cfDNA is required.
- In phase II, if patient has prior tumor sample PTEN/PI3K/AKT gene alterations or immunohistochemistry test with a report, no further tumor sample biomarker test is needed, but the blood cfDNA test is still required in this study. Otherwise, patient should be able to provide archival or biopsy tumor samples for PTEN immunohistochemistry and PTEN/PI3K/AKT gene alterations, and/or the blood sample for PTEN/PI3K/AKT gene alterations for the cell-free DNA (cfDNA) test. The archival tumor tissue sample obtained better within 2 year from study enrollment or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated will be accepted for IHC test and gene sequencing test. Formalin-fixed, paraffin embedded tissue blocks are preferred to be sectioned on the slides.
- Please contact sponsor if patient cannot provide archival or biopsy tumor samples.
- Patients who are suitable for nab-paclitaxel or docetaxel judged by investigator.
- Have measurable disease per RECIST 1.1 as assessed by local radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
- Patients must have an Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2.
- Have adequate organ function as defined below. Specimens must be collected within 10 days prior to the start of study treatment.
- Hematological:
- Absolute neutrophil count (ANC) ≥ 1.5 × 109 /L Platelet count ≥100 × 109 /L Hemoglobin ≥ 90 g/L
- Criteria must be met without granulocyte-colony stimulating factor, erythropoietin dependency and without packed red blood cell transfusion within last 2 weeks.
- Renal Creatinine ≤1.5 × upper limit of normal (ULN) OR Measured or calculated per institutional standard creatinine clearance (glomerular filtration rate can also be used in place of creatinine or creatinine clearance) ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN.
- Hepatic Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN.
- AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases).
- Coagulation International normalized ratio (INR) OR prothrombin time (PT) and Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy, as long as PT or aPTT is within therapeutic range of intended use of anticoagulants.
- Fasting glucose ≤126 mg/dL or ≤7.0 mmol/L for patients without type 2 diabetes and ≤167 mg/dL or ≤9.3 mmol/L for patients with type 2 diabetes; OR glycosylated hemoglobin (HbA1c) ≤8%.
- Life expectancy of 12 weeks or more based on investigator's assessment.
- Patients have recovered from adverse events associated with chemotherapy, radiation and surgical operation as pre-treatment to Grade 1 or lower with CTCAE v5.0 excluding stable symptoms (e.g. alopecia, skin hyperpigmentation.).
- Patients must agree to use effective contraception during the study and for at least 16 weeks after discontinuation as following:
- Total abstinence (if it is their preferred and usual lifestyle)
- An intrauterine device or hormone-releasing system
- A contraceptive implant
- An oral contraceptive (with additional barrier method) OR
- Have a vasectomized partner with confirmed azoospermia.
- Male patients must agree to use an adequate method of contraception.
- Patient is able to swallow and retain oral medication without gastrointestinal diseases to interfere with drug absorption.
Who cannot join
- 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);
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- 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.
- Has an active infection requiring systemic therapy, active syphilis infection, active pulmonary tuberculosis infection，HIV-infection (i.e., HIV 1 or 2 antibody positive).
- New York Heart Association congestive heart failure of grade II or above, unstable angina, myocardial infarction within the past 6 months or serious cardiac arrhythmia associated with significant cardiovascular impairment within the past 6 months.
- Prolongation of corrected QTc interval, as corrected by the Fridericia's correction formula to greater than 450 mSec for males and 470 mSec for females: unless prolonged QTc interval due to right bundle branch block or left bundle branch block with a pacemaker.
- Presence of uncontrolled hypertension (systolic blood pressure (BP) >160 mmHg or diastolic BP>100 mmHg). Patients with a history of hypertension are allowed, provided that BP is controlled to within these limits by anti-hypertensive treatment.
- Has known untreated active Hepatitis B (defined as HBsAg (+) and HBV DNA ≥200 IU/mL (1000 copies/ml)) or active Hepatitis C virus infection (defined as HCV antibody positive and HCV-RNA level above the lower limit of detection).
- Note: Subjects with HBV DNA < 200 IU/ml or below the lower limit of detection are eligible. Those on active HBV therapy with viral loads under 200 IU/mL should stay on the same therapy throughout study treatment.
- Has a known psychiatric or substance abuse disorder that would interfere with the patient's ability to cooperate with the requirements of the study.
- Patients receiving a strong CYP3CA, OATP, BRCP substrate or inducer are not eligible. Please see protocol related section for the list of prohibited medications.
- Has had an allogenic tissue/solid organ transplant.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
- Patient needs radiotherapy during this study.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
China5 sites
Beijing Cancer Hospital
Beijing, Beijing Municipality, 100142
Jilin Cancer Hospital
Changchun, Jilin
West China Second University Hosital, Sichuan University
Chengdu, Sichuan
Chongqing Cancer Hospital
Chongqing, Chengdu
Zhongshan Hospital, Fudan University
Shanghai, Shanghai Municipality
About this study
Official title: 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
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.
Read the 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
- Solid Tumor, NSCLC, Cervical Cancer, Endometrial Cancer, Esophageal Cancer, Gastric and Gastroesophageal Junction Adenocarcinoma
- Being tested
- Afuresertib, Nab paclitaxel, Docetaxel, Sintilimab
- Medical subject headings
- Uterine Cervical Neoplasms, Endometrial Neoplasms, Esophageal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AfuresertibDrug
Also called LAE002
Afuresertib 125 mg PO on days 1-5, 8-12, 15-19 or Afuresertib 125 mg QD
Nab paclitaxelDrug
Nab-paclitaxel 80 mg/M2 IV D1,8, Q3W or 100 mg/M2 IV D1,8, Q3W
DocetaxelDrug
Docetaxel 50 mg/M2 IV D1 Q3W or Docetaxel 60 mg/M2 IV D1 Q3W
SintilimabDrug
Sintilimab 200 mg Q3W
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Afuresertib; Drug: Docetaxel; Drug: Sintilimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 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
Phase I: Anti-tumor activity of Afuresertib in combination with Sintilimab and Nab-paclitaxel or Docetaxel
Measured: 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
Anti-tumor activity of Afuresertib in combination with Sintilimab and Nab-paclitaxel or Docetaxel
Measured: 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
Anti-tumor activity of Afuresertib in combination with Sintilimab and Nab-paclitaxel or Docetaxel
Measured: 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
Anti-tumor activity of Afuresertib in combination with Sintilimab and Nab-paclitaxel or Docetaxel
Measured: 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
Calculated from plasma concentrations of afuresertib obtained at various time points
Measured: Assessed on Day 1, Day 15 of Cycle 1 and Day1 of Cycle 3 (each cycle is 21 days)
Phase II: Overall Response Rate (ORR) based on immune-related iRECIST
Anti-tumor activity of Afuresertib in combination with Sintilimab and Nab-paclitaxel or Docetaxel
Measured: 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)
Phase II: Overall Survival (OS) based on RECIST 1.1
Phase II: Anti-tumor activity of Afuresertib in combination with Sintilimab and Nab-paclitaxel or Docetaxel in EC/CC/ GC/GEJC/EsC/NSCLC
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2022
- Study start1 Jul 2022
- Primary completion25 Jun 2024
- Study completion18 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Laekna Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Lin Shen, Director, Principal investigator, Beijing Cancer Hospital, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05383482
- Sponsor's protocol ID
- LAE202CN2101
- Status last verified
- Nov 2025
- First submitted
- 20 Apr 2022
- Last updated
- 17 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05383482
- Acronym / sponsor ID
- LAE202CN2101
- Conditions
- Solid Tumor, NSCLC, Cervical Cancer, Endometrial Cancer, Esophageal Cancer, Gastric and Gastroesophageal Junction Adenocarcinoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Laekna LimitedIndustry (pharma, biotech, devices)
- Study start
- 1 Jul 2022 (actual)
- Primary completion
- 25 Jun 2024 (actual)
- Study completion
- 18 Jul 2024 (actual)
- First posted
- 20 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Afuresertib in combination with Sintilimab and Nab-paclitaxel | Experimental | Drug: Afuresertib, Drug: Nab paclitaxel, Drug: SintilimabAfuresertib in combination with Sintilimab and Nab-paclitaxel in patients with Endometrial Cancer and Cervical Cancer |
| Afuresertib in combination with Sintilimab and Docetaxel | Experimental | Drug: Afuresertib, Drug: Docetaxel, Drug: SintilimabAfuresertib in combination with Sintilimab and Docetaxel in patients with Gastric and Gastroesophageal Junction Adenocarcinoma, Non-Small Cell Lung Cancer and Esophageal Cancer |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (40 listed)
- 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:
- 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:
Key exclusion criteria (26 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AfuresertibAlso: LAE002Afuresertib 125 mg PO on days 1-5, 8-12, 15-19 or Afuresertib 125 mg QD | Drug | Afuresertib in combination with Sintilimab and Docetaxel, Afuresertib in combination with Sintilimab and Nab-paclitaxel |
| Nab paclitaxelNab-paclitaxel 80 mg/M2 IV D1,8, Q3W or 100 mg/M2 IV D1,8, Q3W | Drug | Afuresertib in combination with Sintilimab and Nab-paclitaxel |
| DocetaxelDocetaxel 50 mg/M2 IV D1 Q3W or Docetaxel 60 mg/M2 IV D1 Q3W | Drug | Afuresertib in combination with Sintilimab and Docetaxel |
| SintilimabSintilimab 200 mg Q3W | Drug | Afuresertib in combination with Sintilimab and Docetaxel, Afuresertib in combination with Sintilimab and Nab-paclitaxel |
Primary outcome
Phase I: Frequency and severity of Adverse Events (AEs),including incidence rate of DLTs
Time frame: Through study completion for an average of 12 months
Phase I: Findings on physical examination, ECG, vital signs, and reports of the laboratory results based on the CTCAE v5.0
Phase I: Recommended Phase II dose
Time frame: about 12 months
Phase I: Determining the RP2D of the Combination therapy for phase II
Phase II: Overall Response Rate (ORR) based on RECIST 1.1
Time frame: 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)
Anti-tumor activity of Afuresertib in combination with Sintilimab and Nab-paclitaxel or Docetaxel in EC/CC/ GC/GEJC/EsC/NSCLC
7 secondary outcomes
Phase I：Overall Response Rate (ORR) based on RECIST 1.1
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Assessed on Day 1, Day 15 of Cycle 1 and Day1 of Cycle 3 (each cycle is 21 days)
Phase II: Overall Response Rate (ORR) based on immune-related iRECIST
Time frame: 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)
Phase II: Overall Survival (OS) based on RECIST 1.1
Time frame: 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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lin Shen, Director principal investigator
Beijing Cancer Hospital, China
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Afuresertib, Nab paclitaxel and Docetaxel in people with Solid Tumor and NSCLC, run by Laekna Limited at 5 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 40 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I: Frequency and severity of Adverse Events (AEs),including incidence rate of DLTs (time frame: Through study completion for an average of 12 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Nov 2025.