Camrelizumab Plus Anlotinib in Patients With Recurrent Sporadic MMRd Endometrial Cancer

NCT05550558 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 2021-KY-111
• Study Type: interventional
• Target: 43
• Locations: 0 countries
• Sites: N/A

Brief Summary

Patients with advanced mismatch repair-deficient (MMRd) or microsatellite instability-high (MSI-H) endometrial cancer (EC) are currently treated as one entity, and immune checkpoint inhibitor (ICI) monotherapy is the treatment of choice. However, different molecular mechanisms drive the development of dMMR/MSI-H tumors, including germline mutations in canonical MMR genes (Lynch syndrome), somatically acquired MMR gene mutations (Lynch-like), and homozygous methylation of the MLH1 gene promoter (sporadic). There is increasing evidence that patients with sporadic MMRd EC have a worse response to ICI monotherapy than those with Lynch/Lynch-like tumors. Antiangiogenic therapy can relieve immunosuppression through blood vessel normalization and the oxygen metabolism pathway, thereby having a synergistic effect with ICIs. Anlotinib is an oral anti-angiogenic tyrosine kinase inhibitor (TKI). Camrelizumab is a fully humanized, high-affinity monoclonal antibody against PD-1. The purpose of this trial is to assess the efficacy and safety and tolerability of anlotinib plus camrelizumab in recurrent EC patients with sporadic MMRd tumors.

Conditions

Endometrial Cancer

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  ORR is defined as the percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria.

  24 months

Secondary Outcomes (5)

• Frequency and severity of adverse events (AEs)

  24 months

• Progression-free Survival (PFS)

  24 months

• Overall Survival (OS)

  24 months

• Disease Control Rate (DCR)

  24 months

• Duration of Response (DOR)

  24 months

Study Arms (1)

Anlotinib + Camrelizumab

EXPERIMENTAL

Anlotinib 12 mg QD p.o for 2 weeks and then stop for 1 week plus Camrelizumab 200 mg (fixed dose) IV every 3 weeks (+/- 3 days) until progression or adverse effects prohibit therapy

Drug: Anlotinib + Camrelizumab

Interventions

Anlotinib + Camrelizumab DRUG

Anlotinib PO plus Camrelizumab IV

Anlotinib + Camrelizumab

Eligibility Criteria

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

You may qualify if:

• Patients must receive have completed at least 1 but no more than 3 prior lines of therapy including at least one prior platinum-based chemotherapy:
• Patients with recurrent endometrial cancer that has failed at least one line of platinum-based chemotherapy;
• Patients with newly diagnosed advanced (metastatic and/or unresectable) disease has persist lesion after frontline treatment with surgery and platinum-based chemotherapy ± radiotherapy;
• Patients with newly diagnosed advanced disease that is not amenable to curative treatment with surgery and/or radiation therapy cannot tolerate chemotherapy;
• Patients may have received prior hormonal therapy for treatment of endometrial carcinoma. All hormonal therapy must be discontinued at least one week prior to the first date of study therapy.
• Histologically proven diagnosis of endometrial cancer.
• Tumors must demonstrate MMRd and MLH1 methylation.
• ° Endometrial tumor MMR and MLH1 methylation status: All participants must be screened using Immunohistochemistry (IHC) for MMR proteins MLH1, MSH2, MSH6, and PMS2. MLH1 gene promoter methylation is performed in tumors exhibiting MLH1 and/or PMS2 IHC loss. MLH1 methylation status is determined by the bisulfite mediated detection of methylated cytosines, as described by Benhamida (Benhamida JK, et al. Reliable Clinical MLH1 Promoter Hypermethylation Assessment Using a High-Throughput Genome-Wide Methylation Array Platform. J Mol Diagn. 2020 Mar;22:368-375. doi: 10.1016/j.jmoldx.2019.11.005).
• All patients must have measurable disease by RECIST 1.1.
• ECOG performance status 0-2.
• Life expectancy ≥ 12 weeks.
• Patients must have adequate organ function:
• Absolute neutrophil count (ANC) ≥ 1.5×10\^9/L;
• Platelet count ≥ 70 × 10\^9/L;
• Hemoglobin ≥ 80 g/L;

You may not qualify if:

• Histologically confirmed diagnosis of sarcoma components including malignant mixed mullerian tumors.
• Patients who have had prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune check point pathways.
• History of severe hypersensitivity reaction (≥Grade 3) to any monoclonal antibody.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure and unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Uncontrolled hypertension (blood pressure \>140/90 mmHg) after adequate treatment.
• Central nervous system diseases, including uncontrollable epilepsy and central nervous system metastases.
• Radiographically confirmed major blood vessel invasion/infiltration.
• Prior chemotherapy, targeted small molecule therapy, bevacizumab, or radiation therapy within 4 weeks of study Day 1 or not recovered from adverse events caused by previously administered treatment.
• Prior hormonal therapy for the treatment of endometrial carcinoma within 1 weeks of study Day 1.
• Known history of Human Immunodeficiency Virus (HIV).
• Known active tuberculosis (TB, Bacillus tuberculosis).
• Known active Hepatitis B or C.
• known active ulcer, or active colitis.
• Received live vaccine within 30 days of planned start of study treatment.
• Patients who have gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of anlotinib.

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

anlotinib; camrelizumab

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Yan-fang Ye, PhD

  Clinical Research Design Division, Sun Yat-sen Memorial Hospital

  STUDY DIRECTOR

Central Study Contacts

Jing Li, MD

CONTACT

008602034071260; lijing228@mail.sysu.edu.cn

Miao-fang Wu, MD

CONTACT

008602034071153; wumiaofang@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2022
• First Posted: September 22, 2022
• Study Start: November 1, 2022
• Primary Completion: November 30, 2025
• Study Completion (Estimated): November 30, 2027
• Last Updated: September 28, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication.
• Access Criteria: email lijing228@mail.sysu.edu.cn