A Phase Ib/II, Open-label Clinical Study to Evaluate the Safety, Tolerability and Antitumor Activities of IN10018 in Combination With Standard Chemotherapy in Subjects With High-grade Serous Epithelial Ovarian Cancer
Overview
- Phase
- Phase 1
- Intervention
- IN10018 in combination with PLD
- Conditions
- Platinum-resistant Ovarian Cancer
- Sponsor
- InxMed (Shanghai) Co., Ltd.
- Enrollment
- 150
- Locations
- 7
- Primary Endpoint
- Incidence of Treatment-Emergent Adverse Events per NCI-CTCAE version 5.0.
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
This is a phase Ib/II, open label clinical study to evaluate the safety, tolerability and antitumor activities of IN10018 in combination with standard chemotherapy in subjects with high-grade serous ovarian cancer (including fallopian tube cancer and primary peritoneum cancer, collectively defined as ovarian cancer).
Detailed Description
Study will evaluate IN10018 in combination with pegylated liposomal doxorubicin (PLD) in subjects with platinum-resistant recurrent ovarian cancer. All the subjects will receive combination therapy until documented progressive disease or unacceptable toxicity.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Ability to understand and willingness to sign informed consent(s). Signed informed consent must be obtained before any study specific procedures, except those procedures used as institutional standard of care falling into the protocol specified window and fulfilling study specific requirements such as tumor imaging.
- •Female subjects ≥ 18 years at the time of signing informed consent.
- •Histologically confirmed epithelia ovarian cancer, fallopian tube cancer or primary peritoneum cancer with the subtype limited to high-grade serous carcinoma (HGSC) only.
- •Subjects with platinum-resistant disease, defined as having relapsed or progressed between 1- 6 months after completion of prior platinum-based therapy (at least 4 cycles).
- •Have maximum total of 5 prior lines of systemic therapy and maximum 2 prior lines of systemic therapy following diagnosis of platinum-resistance.
- •At least one measurable lesion can be accurately measured per RECIST 1.1 as assessed by investigator.
- •ECOG performance status of 0 or
- •Life expectancy of at least 3 months as assessed by investigator.
- •Availability of archival or fresh (newly obtained) tumor tissue sample during Screening Phase: Fresh tumor tissue sample obtained after most recent relapse or progression is preferred; if no sample or not sufficient number of slides can be provided or collected, a joint decision between Sponsor and investigator is needed for the enrollment of this subject.
- •Must have recovered from all AEs due to previous therapies to ≤ Grade 1 (CTCAE 5.0) or stable status as assessed by investigator.
Exclusion Criteria
- •Has had major surgery or significant traumatic injury within 28 days prior to first dose of study treatment, or diagnostic biopsies within 14 days prior to first dose of study treatment.
- •Has received prior systemic anticancer therapy including investigational agents, such as within 14 days or less than 5 half-lives (whichever is shorter) of chemotherapy or targeted therapy, or within 28 days of immunotherapy, prior to first dose of study treatment.
- •Has received prior radiotherapy within 14 days prior to first dose of study treatment.
- •Has received prior treatment of any FAK inhibitor or prior treatment of PLD.
- •Has a known previous or concurrent cancer that is distinct in primary site or histology from current ovarian cancer within 3 years prior to first dose of study treatment, except for curatively treated cancers such as cervical carcinoma in situ.
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- •Has a history of major cardiovascular, cerebrovascular or thromboembolic diseases (e.g., congestive heart failure, acute myocardial infarction, unstable angina, stroke, transient ischemic attack, deep vein thrombosis or pulmonary embolism) within 6 months before first dose of study treatment, or has any of the following abnormality:
- •QTc interval \> 480 msec;
- •Left ventricular ejection fraction (LVEF) \< 50%;
- •New York Heart Association (NYHA) functional classification ≥ Grade 2；
Arms & Interventions
IN10018 in combination with PLD
IN10018 in combination with PLD in platinum-resistant recurrent epithelial ovarian cancer, fallopian tube cancer or primary peritoneum cancer with the subtype limited to high-grade serous carcinoma subjects.
Intervention: IN10018 in combination with PLD
Outcomes
Primary Outcomes
Incidence of Treatment-Emergent Adverse Events per NCI-CTCAE version 5.0.
Time Frame: Up to 24 months
Incidence of Treatment-Emergent Adverse Events per NCI-CTCAE version 5.0.
Recommended phase 2 dose (RP2D) of the combination.
Time Frame: Up to 2 months
Defined based on the incidence of dose limiting toxicities (DLTs).
Objective response rate (ORR) as assessed by investigator.
Time Frame: Up to 24 months
ORR is defined as the proportion of subjects with complete response (CR) and partial response (PR), as assessed by investigator per RECIST 1.1.
Secondary Outcomes
- Progression free survival (PFS) as assessed by investigator and BICR.(Up to 24 months)
- Overall survival (OS)(Up to 24 months)
- Objective response rate (ORR) as assessed by blinded independent central review (BICR).(Up to 24 months)
- Duration of response (DOR) as assessed by investigator and BICR.(Up to 24 months)
- CA 125 response rate per Gynecological Cancer Inter-group (GCIG) criteria.(Up to 24 months)
- Disease control rate (DCR) as assessed by investigator and BICR.(Up to 24 months)