Qi Zhou

Suvemcitug plus chemotherapy in women with platinum-resistant recurrent ovarian cancer: the SCORES randomized, double-blinded, phase 3 trial

Abstract In the SCORES study ( NCT04908787 ), women with ovarian cancer that progressed within 6 months after completing platinum-based therapy were randomized (2:1) to receive suvemcitug (1.5 mg kg −1 ), an antibody to vascular endothelial growth factor or placebo every 2 weeks, with chemotherapy (paclitaxel, topotecan or PEGylated liposomal doxorubicin). The primary endpoint was progression-free survival (PFS). The key secondary endpoint was overall survival (OS). Other secondary endpoints included objective response rate, disease control rate, duration of response, quality of life, safety, pharmacokinetics and antidrug antibodies. Between June 5, 2021 and October 11, 2024, 421 participants were randomized (49.4% and 49.4% previously exposed to antiangiogenic agents and poly(ADP-ribose) polymerase inhibitors, respectively). Median PFS was 5.5 and 2.7 months in the suvemcitug and placebo arms, respectively (hazard ratio: 0.46, 95% confidence interval (CI): 0.35–0.60, P  < 0.001), meeting the primary endpoint. Median OS was 15.3 versus 14.0 months, respectively (hazard ratio: 0.77, 95% CI: 0.60–0.99, P  = 0.03). Decreased neutrophil count and decreased white blood cell count were the most common grade ≥3 treatment-emergent adverse events (TEAEs) in the suvemcitug arm. No suvemcitug-related grade 5 TEAE occurred. In conclusion, the addition of suvemcitug to chemotherapy significantly improved PFS and OS, with tolerable toxicities.

Fruquintinib plus sintilimab in patients with advanced endometrial cancer with mismatch-repair proficient status: a multicenter, single-arm, phase Ib/II trial

This report presents the primary analysis of the endometrial cancer (EMC) cohort of FRUSICA-1 (ClinicalTrials.gov identifier, NCT03903705), a multicenter, single-arm, phase Ib/II study evaluating fruquintinib plus sintilimab. The cohort included Chinese patients with inoperable or advanced mismatch-repair proficient (pMMR) EMC who had progressed on or could not tolerate up to two prior platinum-based therapies, and comprised exploratory and pivotal phases. Patients received fruquintinib (5 mg orally once daily on a 2 weeks on/1 week off schedule) plus sintilimab (200 mg intravenously once every 3 weeks). The primary endpoint was objective response rate (ORR) assessed by an independent review committee (IRC). Secondary endpoints included ORR as assessed by the investigator, disease control rate, time to response, duration of response, progression-free survival (PFS) and tumor shrinkage as assessed by both the IRC and investigator, overall survival, and safety. By May 15, 2024, 98 patients with pMMR EMC were enrolled and treated. IRC-assessed ORR was 32.7% (95% confidence interval [CI] 23.5-42.9) for the total pMMR population (n = 98) and 31.6% (95% CI 21.4-43.3) for the pivotal population (n = 76). Median PFS was 8.6 months (95% CI 5.5-16.6) for the total population and 7.1 months (95% CI 5.4-16.6) for the pivotal population. The most common grade ≥3 treatment-related adverse event was hypertension (17.3%). In conclusion, fruquintinib plus sintilimab showed promising efficacy and tolerable safety in previously treated, advanced pMMR EMC.

One‐stop molecular classification of endometrial carcinoma using comprehensive next‐generation sequencing

AbstractThis study aims to investigate the feasibility of molecular classification using only comprehensive next‐generation sequencing‐based techniques and its relationship with survival outcomes in patients with endometrial cancer. Paired tumor‐normal sequencing data of 1021 cancer‐related genes using tumor tissues or peripheral blood samples and clinical data were retrospectively collected from a cohort of endometrial cancers. The microsatellite instability status was inferred using the MSIsensor (v0.5) with a cut‐off of 8%. Sixty patients were classified into four groups: POLEMUT group (13.3%), MSI‐H group (20%), TP53WT group (45%) and TP53MUT group (21.7%). Patients within TP53MUT group were more common in serous carcinoma compared to endometrioid carcinoma (P = .0098). TP53WT was significantly correlated with early stage and low grade. TP53MUT group was associated with significantly worse DFS compared to MSI‐H group and TP53WT group (P = .014 and .004, respectively). Comprehensive next‐generation sequencing is a reliable and simple method to stratify the prognosis of endometrial carcinoma. It can be potentially used to guide treatment of patients with endometrial cancer in routine practice.

Genetic analysis of cervical cancer with lymph node metastasis

To find out the differences in gene characteristics between cervical cancer patients with and without lymph node metastasis, and to provide reference for therapy. From January 2018 to June 2022, recurrent cervical cancer patients 39 cases with lymph node metastasis and 73 cases without lymph node metastasis underwent testing of 1,021 cancer-related genes by next-generation sequencing. Maftools software was used to analyze somatic single nucleotide/insertion-deletion variation mutation, co-occurring mutation, cosmic mutation characteristics, oncogenic signaling pathways. EP300 and FBXW7 were significantly enriched in lymph node-positive patients. Lymph node-positive patients with EP300 or FBXW7 mutations had lower overall survival (OS) after recurrence. Both lymph node-positive and -negative patients had plenty of co-occurring mutations but few mutually exclusive mutations. Lymph node-positive co-occurring mutation number ≥6 had lower OS, while lymph node-negative co-occurring mutation number ≥3 had lower OS after recurrence. The etiology of SBS3 was defects in DNA double strand break repair by homologous recombination, which exclusively exist in lymph node-positive patients. There was no difference in median tumor mutation burden (TMB) between positive and negative lymph nodes, but TMB was significantly associated with PIK3CA mutation. The somatic SNV/Indels of EP300 and FBXW7, SBS3 homologous recombination-mediated DNA repair defect were enriched in lymph node-positive patients. For lymph node-positive patients, EP300 or FBXW7 mutations predicted poor prognosis. No matter lymph node-positive or negative, more co-occurring mutation number predicted poor prognosis. PIK3CA mutation may account for the higher TMB and help identify patients who benefit from immunotherapy.

A clinical study of pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) in preventing neutropenia during concurrent chemoradiotherapy of cervical cancer

Abstract Purpose To evaluate the effectiveness and safety of pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) in preventing neutropenia during chemoradiotherapy in patients with cervical cancer. Methods From August 2018 to April 2020, 60 patients who were pathologically confirmed as cervical cancer were randomly divided into two groups at a ratio of 2:1: PEG-modified-rhG-CSF experimental group and control group. The primary endpoints were the incidence of grade 3–4 neutropenia. Secondary endpoints included the duration of grade 3–4 neutropenia, the incidence of grade 4 neutropenia, the incidence of febrile neutropenia (FN), delay rate of chemotherapy, prolonged time of chemotherapy, time to complete radiotherapy and safety. Results The incidence of grade 3–4 neutropenia in the experimental group was significantly lower than the control group (10% vs. 77.78%, P < 0.001). However, there was no statistical significance between the two groups in the duration of grade 3–4 neutropenia (3.75 days vs. 5.07 days, P = 0.871). The experimental group was better than the control group in the incidence of grade 4 neutropenia, the incidence of FN and delay rate of chemotherapy, and the difference was statistically significant (P < 0.05). Besides, the prolonged time of chemotherapy and the time to complete radiotherapy in the experimental group were less than those in the control group, but the difference was not statistically significant (P > 0.05). The incidence of adverse events in the experimental group and control group were 55.00 and 94.44%, respectively, and the difference was statistically significant (P = 0.003). Conclusion PEG-rhG-CSF preventive treatment used in the course of chemoradiotherapy for patients with cervical cancer can reduce the incidence of neutropenia and improve the incidence of delayed chemotherapy cycles. Trial registration ClinicalTrials.gov, NCT04542356. Registered 9 September 2020 - Retrospectively registered.

A multicenter phase 2 trial of camrelizumab plus famitinib for women with recurrent or metastatic cervical squamous cell carcinoma

AbstractThis phase 2 study assesses the efficacy and safety of camrelizumab (an anti-PD-1 antibody) plus famitinib (anti-angiogenic agent) in women with pretreated recurrent or metastatic cervical cancer (ClinicalTrials.gov NCT03827837). Patients with histologically or cytologically confirmed cervical squamous cell carcinoma experiencing relapse or progression during or after 1–2 lines of systemic therapy for recurrent or metastatic disease are enrolled. Eligible patients receive camrelizumab 200 mg intravenously on day 1 of each 3-week cycle plus famitinib 20 mg orally once daily. The primary endpoint is the objective response rate. Secondary endpoints are duration of response, disease control rate, time to response, progression-free survival, overall survival, and safety. The trial has met pre-specified endpoint. Thirty-three patients are enrolled; median follow-up lasts for 13.6 months (interquartile range: 10.0–23.6). Objective responses are observed in 13 (39.4%, 95% confidence interval [CI]: 22.9–57.9) patients; the 12-month duration of response rate is 74.1% (95% CI: 39.1–90.9). Median progression-free survival is 10.3 months (95% CI: 3.5–not reached) and the 12-month overall survival rate is 77.7% (95% CI: 58.9–88.7). All patients experience treatment-related adverse events; grade ≥3 events occur in 26 (78.8%) patients. Treatment-related serious adverse events and deaths are observed in 9 (27.3%) and 2 (6.1%) patients, respectively. Camrelizumab plus famitinib shows promising antitumor activity with a manageable and tolerable safety profile in patients with pretreated recurrent or metastatic cervical squamous cell carcinoma. This combination may represent a treatment option for this population.

Efficacy and Safety of the Anti–PD-L1 mAb Socazolimab for Recurrent or Metastatic Cervical Cancer: a Phase I Dose-Escalation and Expansion Study

Abstract Purpose: This study (ClinicalTrials.gov identifier, NCT03676959) is an open, phase I dose-escalation and expansion study investigating the safety and efficacy of the recombinant, fully human anti–programmed death ligand 1 (PD-L1) mAb socazolimab in patients diagnosed with recurrent or metastatic cervical cancer. Patients and Methods: Patients received socazolimab every 2 weeks until disease progression. The study was divided into a dose-escalation phase and a dose-expansion phase. Safety and tolerability were primary endpoints of the dose-escalation phase. The primary endpoints of the dose-expansion phase were safety and the objective response rate (ORR) of the 5 mg/kg dose. Efficacy was assessed by the third-party independent review committee (IRC) using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Results: 104 patients were successfully enrolled into the study. Twelve patients were included in the dose-escalation phase, with one complete response and two partial responses in the 5 mg/kg treatment group. Ninety-two patients (5 mg/kg) were enrolled in the dose-expansion phase. Fifty-four patients (59.3%) had baseline PD-L1–positive tumor expression (combined positive score ≥1). ORR was 15.4% [95% confidence interval (CI), 8.7%–24.5%]. Median PFS was 4.44 months (95% CI, 2.37–5.75 months), and the median OS was 14.72 months (95% CI, 9.59–NE months). ORR of PD-L1–positive patients was 16.7%, and the ORR of PD-L1–negative patients was 17.9%. No treatment-related deaths occurred. Conclusions: Our study demonstrates that socazolimab has durable safety and efficacy for the treatment of recurrent or metastatic cervical cancer and exhibits a safety profile similar to other anti–PD-1/PD-L1 mAbs.

Efficacy and safety of zimberelimab (GLS-010) monotherapy in patients with recurrent or metastatic cervical cancer: a multicenter, single-arm, phase II study

There is an unmet need to improve clinical outcomes for patients with recurrent/metastatic cervical cancer. Checkpoint inhibitors represent a promising treatment strategy. We evaluated the safety and anti-tumor activity of zimberelimab, an anti-programmed cell death protein-1 antibody, in patients with previously treated, recurrent, metastatic cervical cancer. This phase II, single-arm, open-label study used a Simon two-stage minimax design. Eligible patients were women aged 18-75 years with programmed death ligand-1-positive recurrent or metastatic cervical cancer that had progressed after first- or subsequent-line chemotherapy (Eastern Cooperative Oncology Group (ECOG) performance status 0-1). Patients received intravenous zimberelimab (240 mg every 2 weeks) for 2 years until disease progression, intolerable adverse effects, or withdrawal from the study. The primary endpoint was objective response rate assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, by an independent review committee. A total of 105 patients were enrolled. Median age was 51 (range, 31-75) years; 63.8% had an ECOG performance status of 1. The median number of previous treatment lines was 1 (range, 1-4). Median follow-up was 16.9 (range, 16.3-18.4) months. The objective response rate was 27.6%, and the disease control rate was 55.2%. Median duration of response was not reached. Median overall survival was 16.8 months, and median progression-free survival was 3.7 months. The incidence of treatment-related adverse events of any grade was 78.1%, of which the most common were hypothyroidism (26.7%) and anemia (19.0%). Zimberelimab monotherapy demonstrated durable anti-tumor activity and an acceptable safety profile in patients with cervical cancer. NCT03972722.

QL1604 plus paclitaxel-cisplatin/carboplatin in patients with recurrent or metastatic cervical cancer: an open-label, single-arm, phase II trial

QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46). The median duration of response was 9.6 months (95% confidence interval [CI]=5.5-not estimable). The median progression-free survival was 8.1 months (95% CI=5.7-14.0). Forty-five (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can't tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.

A Single-arm, Multicenter Clinical Study of Becotatug Vedotin Combined With Zimberelimab in the Treatment of Recurrent and Metastatic Cervical Cancer, Vulvar Cancer and Vaginal Cancer

This is a prospective, multicenter, single-arm clinical trial investigating Becotatug Vedotin in combination with Zimberelimab for the treatment of patients with recurrent and metastatic cervical cancer, vulvar cancer, and vaginal cancer. A total of 30 patients are expected to be enrolled. The study consists of a screening period (within 28 days), a treatment period, and a follow-up period (safety follow-up and survival follow-up). Trial treatment will continue until the patient has received Becotatug Vedotin for 1 year, or until disease progression, unacceptable toxicity, withdrawal of informed consent, or death, whichever occurs first. Subjects will sign the informed consent form and undergo baseline examinations during the screening period. Patients who meet the inclusion and exclusion criteria will enter the treatment period. All subjects will complete the relevant examinations specified in the protocol during treatment to observe safety, tolerability, and efficacy.

Study of GLS-010 Injection in Patients With Recurrent or Metastatic Cervical Cancer

Patients with recurrent or metastatic cervical cancer，and will be treated with GLS-010.

Famitinib Plus Anti-PD1 Therapy for Advanced Urinary System Tumor, Advanced Gynecological Tumors

Phase II multi-chort, adaptive two-stage, open label, nonrandomized study. The aim of our study is to evaluate the efficacy and safety of anti-PD-1 antibody SHR-1210(Camrelizumab) in combination with a small-molecule multikinase inhibitor Famitinib in subjects with advanced RCC/UC/CC/EC and recurrent OC. chort1: Renal Cell Carcinoma (RCC) chort2: Urothelial Carcinoma(UC) chort3: Ovarian Cancer (OC) chort4: Cervical Cancer (CC) chort5: Endometrial Cancer (EC)

A Clinical Study of PD-L1 Antibody ZKAB001（Drug Code） in Recurrent or Metastatic Cervical Cancer

This is a Phase 1, open-label, dose-escalation, and multidose study, aiming to investigate the safety, tolerability and pharmacokinetics(PK) of ZKAB001 (a fully human monoclonal antibody targeting the Programmed Death - Ligand 1 (PD-L1) membrane receptor on T lymphocytes and other cells of the immune system) administered every 14 days in subjects with recurrent or metastatic cervical cancer.

Study on the Efficacy and Safety of PEG-rhG-CSF in Preventing Neutropenia During Concurrent Chemoradiotherapy of Cervical Cancer

This randomized controlled prospective study aims to explore the efficacy and safety of using (PEGylated Recombinant Human Granulocyte Stimulating Factor) PEG-rhG-CSF to prevent neutropenia during concurrent chemoradiotherapy of paclitaxel and cisplatin (TP) regimen for cervical cancer. To find out the best time to use PEG-rhG CSF, and to explore investigate the effect of PEG-rhG-CSF on long-term bone marrow function in the process of concurrent chemoradiotherapy, and finally to explore the clinical feasibility of using PEG-rhG-CSF to prevent neutropenia during concurrent chemoradiotherapy of TP regimen for cervical cancer.