Clinical trial NCT06173037: RC88 in Platinum-Resistant Recurrent Epithelial Ovarian Cancer, Fallopian Tube Cancer, and Primary Peritoneal Cancer
Official title: A Multicenter, Single-arm, Phase 2 Study to Evaluate the Efficacy, Safety and Pharmacokinetics of RC88 Monotherapy in Platinum-resistant Recurrent Epithelial Ovarian, Fallopian Tube and Primary Peritoneal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Primary Peritoneal Cancer
Fallopian Tube Cancer
Epithelial Ovarian Cancer
Keywords: Primary Peritoneal Cancer
Fallopian Tube Cancer
Epithelial Ovarian Cancer
Lead sponsor: RemeGen Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-12-15
Enrollment: 88
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of RC88 monotherapy in subjects with Platinum-Resistant Recurrent Epithelial Ovarian, Fallopian Tube and Primary Peritoneal Cancer.


Eligibility criteria: Inclusion Criteria:

1. Agree to participate in the study and sign an Informed Consent Form;
2. Female subjects aged 18 years or older at the time of signing the Informed Consent Form;
3. Histology confirmed high grade serous ovarian, fallopian tube or primary peritoneal cancer;
4. Must be newly developed platinum-resistant (Must not have received systemic therapy after developing platinum resistance status);
5. Received at least 3 prior lines of systemic therapies；
6. Imaging evidence of disease progression during or at the end of last-line therapy;
7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
8. Life expectancy of at least 12 weeks;
9. Subjects are willing to provide archival tumor tissue samples or accept a low-risk routine medical procedure to collect the fresh biopsy sample for immunohistochemical (IHC) MSLN testing;
10. Measurable lesion according to RECIST v1.1；
11. The interval between previous focal radiotherapy and the first dose should be at least 2 weeks；
12. Have laboratory tests that meet the relevant requirements to demonstrate adequate organ function;
13. Subjects of childbearing potential are required to use effective contraception from the time of informed consent and continuing through 6 months after the final dose of study intervention; Fertile subjects included those who were not menopausal or had been menopausal for less than 2 years and had not undergone bilateral adnexectomy or hysterectomy；Subjects of childbearing potential must have a negative pregnancy test within 7 days prior to the first dose of study intervention.

Exclusion Criteria:

1. The presence of clinically uncontrollable third-space fluids, such as massive pleural effusion or pericardial effusion accompanied by clinical symptoms or requiring symptomatic management; and ascites that cannot be effectively controlled with treatment;
2. Subjects with asymptomatic brain metastases who have received prior treatment may participate in this study if they meet all the following criteria:

   * Only supratentorial and/or cerebellar metastases are present.
   * Corticosteroids should be discontinued for at least 7 days prior to the first dose;
   * No disease progression is observed on imaging from completion of brain-directed therapy until randomization compared to pre-treatment imaging (at least 4 weeks interval).
   * Subjects must undergo radiotherapy and/or surgery for brain metastases if new asymptomatic brain metastases are detected during screening period.
3. Subjects with a history of other invasive malignancies within 3 years prior to the first dose, except for adequately treated papillary thyroid carcinoma, basal cell or squamous cell skin cancers without evidence of recurrence, and other adequately treated carcinoma in situ without evidence of disease recurrence；
4. Subjects with ongoing clinically significant toxicity associated with prior treatment that has not resolved to Grade 0 or 1 by NCI CTCAE 5.0;
5. Subjects who have received systemic anti-tumor therapy (including chemotherapy, targeted therapy, biologic therapy, hormonal therapy, etc.) within 28 days or 5 half-lives of prior therapy (whichever is shorter) prior to first dose;
6. Subjects who have received herbal or proprietary Chinese medicines for tumor control within 14 days prior to the first dose;
7. Subjects who have received previous mesothelin target-related drugs or MMAE, MMAF, DM1, DM4 and other microtubule inhibitor ADCs；
8. Subjects with clinical symptoms or signs of gastrointestinal obstruction;
9. History of cirrhotic liver disease (Child-Pugh Class B or C);
10. Subjects with immunodeficiency diseases, currently receiving systemic glucocorticoid therapy (dose\>10 mg/d of prednisone or equivalent dose among drugs in the same class), or receiving immune suppressant therapy within 7 days prior to the first dose；
11. Major surgery within 4 weeks and no fully recovered prior to the first dose or anticipation of surgery；
12. Patients with active or progressive infection that requiring systemic therapy within 14 days prior to first dose, such as active tuberculosis;
13. serum virological testing (based on study center normal values)

    * Positive results of Hepatitis B virus surface antigen (HBsAg) should be further tested for HBV DNA, HBV DNA \> 200IU/ml or 2000 copies /ml cannot be enrolled. However, if subjects received nucleotide-based antiviral therapy and test result below the criteria above, they could be enrolled;
    * Positive results of Hepatitis C antibody (HCVAb) (HCV RNA\>103 copies/ml) cannot be enrolled. However, if subjects received nucleotide-based antiviral therapy and the test result below the criteria above, they could be enrolled;
    * Positive results for human immunodeficiency virus antibody (HIVAb).
14. Subjects with prior allogeneic haematopoietic stem cell transplantation or solid organ transplantation, or those who are waiting for organ transplantation;
15. Uncontrolled or significant cardiovascular and cerebrovascular diseases;
16. A history of interstitial lung disease requiring treatment or currently having a severe pulmonary disease, including but not limited to interstitial lung disease;
17. In the investigator's opinion, any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory findings, that raise reasonable suspicion of a disease or condition affecting the interpretation of the study results or placing the patient at high risk of participating in the study；
18. Subjects with active corneal disease and those who, in the judgement of the ophthalmologist, are unsuitable for inclusion by funduscopic examination and other ocular related examinations；
19. Subjects with known allergies to RC88 or its excipients or have had a history of severe allergic reactions to the other monoclonal antibodies or chemotherapies;
20. Subjects who have received a live or live-attenuated vaccine within 4 weeks prior to the first dose or plan to receive the above vaccines during the study；
21. Known psychiatric or substance abuse disorders that may have an impact on compliance with the study requirements.
22. Pregnant and/or breast-feeding women；
23. The subject's compliance are estimated to be insufficient to participate in this study, or other factors that, in the investigator's opinion, make the subjects unsuitable for participation of this study.

Primary outcomes:
measure: Overall Response Rate (ORR) by Independent Review Committee (IRC)
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Overall Response Rate (ORR) by investigator
timeFrame: Up to approximately 2 years
measure: Duration of response (DOR) by Independent Review Committee (IRC)
timeFrame: Up to approximately 2 years
measure: Duration of response (DOR) by investigator
timeFrame: Up to approximately 2 years
measure: Progression-free survival (PFS) by Independent Review Committee (IRC)
timeFrame: Up to approximately 2 years
measure: Progression-free survival (PFS) by investigator
timeFrame: Up to approximately 2 years
measure: Overall survival (OS)
timeFrame: Up to approximately 2 years
measure: CA-125 relieve defined by GCIG
timeFrame: Up to approximately 2 years
measure: The peak and trough concentrations of RC88 binding antibody (ADC), total antibody (TAb) and free MMAE
timeFrame: Up to approximately 2 years
measure: Incidence of Anti-Drug Antibodies (ADA), titers, and/or neutralizing antibodies (NAb) Rate etc.
timeFrame: Up to approximately 2 years
measure: Safety: The types, incidence, correlation, and severity of various adverse events (AES), as well as the types, incidence, and severity of laboratory abnormalities
timeFrame: Up to approximately 2 years
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Xingtai
country: China
facility: Xingtai People's Hospital
state: Hebei
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Xiangyang
country: China
facility: Xiangyang Central Hospital
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Zhongda Hospital Southeast University
state: Jiangsu
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Jinan
country: China
facility: Shandong Cancer Hospital, Shandong Cancer Institute
state: Shandong
city: Qingdao
country: China
facility: Qingdao Central Hospital
state: Shandong
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shangdong
city: Shanghai
country: China
facility: Obstetrics & Gynecology Hospital of Fudan University
state: Shanghai
city: Taiyuan
country: China
facility: Second hospital of Shanxi Medical University
state: Shanxi
city: Chengdu
country: China
facility: The West China Second University Hospital of Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
state: Tianjin
city: Kunming
country: China
facility: Yunnan Cancer Hospital
state: Yunnan
city: Hangzhou
country: China
facility: The Second Affiliated Hospital Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: Yuankai Shi, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Qilu Hospital of Shandong University
name: Beihua Kong, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Qilu Hospital of Shandong University
name: Jie Jiang, M.D
role: PRINCIPAL_INVESTIGATOR
References: