A phase 1/2 clinical trial examining the combination of afuresertib, sintilimab, and chemotherapy in patients with specific solid tumors who were resistant to anti-PD-1/PD-L1 therapy has dosed its first patient.
Trial Name: Afuresertib +Sintilimab+Chemotherapy in Patients With Selected Solid Tumors That Resistance to Prior Anti-PD-1/PD-L1
ClinicalTrials.gov Indentifier: NCT05383482
Completion Date: December 31, 2025
Recruitment Status: Recruiting
Sponsor: Laekna Limited
Recruitment Contacts: Shimei Liu (86-021-50716089) shimei.liu@laeknatp.com and Li Qiu (86-021-50716089) li.qiu@laeknatp.com
The first patient has been dosed in a phase 1/2 clinical trial (NCT05383482) of the combination therapy consisting of afuresertib, sintilimab (Tyvyt), and chemotherapy in patients with specific solid tumors who were resistant to anti-PD-1/PD-L1 therapy, according to Innovent Biologics, Inc.1
This multi-center phase 1/2 clinical study will assess the recommended phase 2 dose (RP2D) of the combination along with its safety, tolerability and anti-tumor activity in this patient population.2
Afuresertib, an AKT inhibitor, is the focus of the study as it is a potential new therapy for drug resistant-cancer. The trial aims to address the unmet medical needs in cancer immunotherapy resistance and bring hope to patients with solid tumors who have previously received prior anti-PD-1/PD-L1 treatments.
“Immunotherapy plays an increasingly important role in the treatment of recurrent or metastatic cervical cancer, and there is a huge unmet need. With the launch of new immunosuppressants, they've been applied to more patients and become essential for the treatment of cervical cancer,” said Rutie Yin, PhD, investigator of the center where the first patient was dosed and director of the Department of Chemoradiotherapy Oncology at the West China Second Hospital of Sichuan University, in the press release. “AKT inhibitor, a serine/threonine-specific protein kinase, is considered a potential new target for cancer treatment as results of multiple preclinical studies showed that inhibition of AKT could restore the sensitivity of cancer cells to anti-tumor therapies. We look forward to the progress of the clinical trial and hope it will bring new breakthroughs to the later-line treatment of cervical cancer in China."
Afuresertib is an investigational highly selective adenosine triphosphate (ATP) competitive AKT inhibitor which has been examined in over 10 clinical trials in order to determine its safety and efficacy profiles. In a phase 1b trial (NCT01653912), the inhibitor demonstrated potential anti-tumor efficacy in patients with platinum-resistant ovarian cancer with an overall response rate (ORR) of 32.1% and progression-free survival (PFS) of 7.1 months.
Pre-clinical studies also showed afuresertib to restore platinum/paclitaxel sensitivity in PROC cell lines, and the therapeutic potential of combining afuresertib and LAE001, an investigational potential first-in-class next-generation androgen synthesis inhibitor, was observed. Further,synergistic anti-tumor efficacy was demonstrated, according to findings from a completed phase 1 study as well as an ongoing phase 2 study in metastatic castration-resistant prostate cancer (mCRPC).
The single-arm, open-label, dose-escalation study aims to find the RP2D of afuresertib in combination with sintilimab and nab-paclitaxel or docetaxel, respectively, as well as the maximum tolerated dose (MTD). Further, the study will characterize the pharmacokinetics (PK) profile of afuresertib in phase 1 and will evaluate the clinical efficacy and safety of the combination therapy within phase 2.
In phase 2, the study population will consist of patients with 1 of the 5 selected cancers being assessed which include non—small cell lung cancer (NSCLC), gastric cancer/gastroesophageal junction cancer (GEJC), esophageal cancer, cervical cancer, and endometrial cancer.
Patients enrolled in the first arm are those with endometrial and cervical cancer and will receive afuresertib in combination with sintilimab and nab-paclitaxel. Those in the second arm will be patients with gastric and GEJC, NSCLC, and esophageal cancer, and will be given afuresertib in combination with sintilimab and docetaxel.
Enrollment is open to patients aged 18 years and older with a histology confirmed diagnosis of one of the locally advanced or metastatic solid tumors resistant to the prior anti-PD-1/PL-1 treatments. Further eligibility requirements include being suitable for nab-paclitaxel or docetaxel judged by investigator, measurable disease per RECIST 1.1 as assessed by local radiology, an ECOG performance status of 0-2, adequate organ function, and a life expectancy of 12 weeks or greater.
Patients must also 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 and agree to use contraception during the study period and for at least 16 weeks after discontinuation.
Primary end points of the phase 1 dose-escalation portion of the study are MTD, RP2D, and frequency of adverse events while the primary end point of the phase 2 portion of the study is ORR. Secondary end points for phase 1 include ORR, disease control rate, duration of response, PFS, and assessing PK parameters. The secondary end points for phase 2 include ORR and overall survival. The study is expected to be extended as a multi-regional clinical trial at the pivotal stage.
"Innovation never stops in oncology as we are always looking for new ways to treat cancer patients. Based on results from the preclinical and clinical studies, the combination of an immune checkpoint inhibitor, an AKT inhibitor and taxanes shows potential to be a new treatment option for patients who were resistant to immune checkpoint inhibitors. The trial conducted by Laekna and Innovent aims to explore this innovative combination therapy and validate this new promising solution. There is a significant clinical need for patients with digestive system and gynecologic solid tumors in China; we hope to see that AKT-targeting therapy will prove to be an effective strategy to overcome drug resistance," stated Lin Shen, PhD, principal investigator of the study, director of the Department of Gastrointestinal Oncology of from Beijing Cancer Hospital, in the press release.
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