Phase I Study to Evaluate SCR-6852 Alone or in Combination in ER+, HER2- Locally Advanced or Metastatic Breast Cancer
Study Details
Study Description
Brief Summary
This study is a multi-center, open-label, Phase 1 clinical study to evaluate the safety, kinetics and anti-tumor efficacy of SCR-6852 and SCR-6852 in combination with palbociclib in subjects with estrogen receptor (ER) -positive, human epidermal growth factor receptor (HER-2) -negative locally advanced or metastatic breast cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
The study is comprised of two parts: Phase Ia and Phase Ib. Phase 1a is a dose-escalating phase of SCR-6852 to determine the MTD and/or RP2D, safety, and tolerability of SCR-6852; Phase 1b is a 2-part dose-finding phase of SCR-6852 in combination with palbociclib to determine the MTD and/or RP2D, safety, and tolerability of SCR-6852 in combination with palbociclib; and the second part of Phase Ib is a dose-expansion phase of SCR-6852 in combination with palbociclib to explore the efficacy of combination therapy in locally advanced or metastatic breast cancer.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: SCR-6852 Phase Ia SCR-6852 monotherapy dose escalation and expansion |
Drug: SCR-6852
SCR-6852 is an oral, selective estrogen receptor degrader (SERD)
Other Names:
|
| Experimental: SCR-6852+palbociclib Phase Ib SCR6852 with palbociclib dose escalation and expansion |
Drug: SCR-6852
SCR-6852 is an oral, selective estrogen receptor degrader (SERD)
Other Names:
Drug: Palbociclib
palbociclib is a selective inhibitor of cyclin D-cyclin-dependent kinase (CDK) 4/6
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Maximum Tolerated Dose [At the end of Cycle 1 (each cycle is 28 days)]
Dose Escalation: Maximum Tolerated Dose (MTD) of SCR-6852 When Administered as a Single Agent or in Combination with Palbociclib
- recommended phase 2 Dose [At the end of Cycle 1 (each cycle is 28 days)]
Dose Escalation: recommended phase 2 Dose (RP2D) of SCR-6852 When Administered as a Single Agent or in Combination with Palbociclib
- Dose-Limiting Toxicities [At the end of Cycle 1 (each cycle is 28 days)]
Dose Escalation: Number of Participants with Dose-Limiting Toxicities When SCR-6852 is Administered as a Single Agent or in Combination with Palbociclib
- objective response rate [through study completion, an average of 1 year]
Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumor (RECIST 1.1) or Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM)
Secondary Outcome Measures
- Adverse event [From Baseline until 30 days after the last dose of study treatment]
Number of Participants with Adverse Events by Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0)
- Number of Participants with Clinical Laboratory Abnormalities [From Baseline until 30 days after the last dose of study treatment]
Number of Participants with Clinical Laboratory Abnormalities by Highest Grade According to NCI-CTCAE v5.0
- Peak Plasma Concentration (Cmax) of SCR-6852 as monotherapy or combination with palbociclib [At the end of Cycle 4 (each cycle is 28 days)]
Peak Plasma Concentration (Cmax)
- Time of Peak Plasma Concentration (Tmax) of SCR-6852 as monotherapy or combination with palbociclib [At the end of Cycle 4 (each cycle is 28 days)]
Time of Peak Plasma Concentration (Tmax)
- Area under the plasma concentration versus time curve (AUC) of SCR-6852 as monotherapy or combination with palbociclib [At the end of Cycle 4 (each cycle is 28 days)]
Area under the plasma concentration versus time curve (AUC)
- clinical benefit rate [through study completion, an average of 1 year]
Antitumour activity by evaluation of clinical benefit rate assessments using Response Evaluation Criteria in breast cancer (RECIST 1.1)or Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM)
- disease control rate [through study completion, an average of 1 year]
Antitumour activity by evaluation of disease control rate assessments using Response Evaluation Criteria in breast cancer (RECIST 1.1)or Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM)
- duration of response [through study completion, an average of 1 year]
Antitumour activity by evaluation of duration of response assessments using Response Evaluation Criteria in breast cancer (RECIST 1.1)or Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM)
- progression free survival [From date of C1D1 until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months]
Antitumour activity by evaluation of progression free survival assessments using Response Evaluation Criteria in breast cancer (RECIST 1.1)or Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM)
- time to progression [From date of C1D1 until the date of first documented progression, assessed up to100 months]
Antitumour activity by evaluation of time to progression assessments using Response Evaluation Criteria in breast cancer (RECIST 1.1)or Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM)
- time to response [through study completion, an average of 1 year]
Antitumour activity by evaluation of time to response assessments using Response Evaluation Criteria in breast cancer (RECIST 1.1)or Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM)
- overall survival [From date of C1D1 until the date of death from any cause, assessed up to 100 months]
Antitumour activity by evaluation of overall survival assessments
Eligibility Criteria
Criteria
key Inclusion Criteria:
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voluntary participation in clinical trials and signature of informed consent.
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age ≥ 18 years, male or female.
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Histologically or cytologically confirmed metastatic/locally advanced ER-positive, HER-2 negative breast cancer subjects.
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previous treatment meets the criteria of the protocol defined.
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ECOG score of 0 or 1 .
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at least one measurable lesion that meets RECISTv1.1 criteria.
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expected survival ≥ 12 weeks.
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Adequate organ and bone marrow function.
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Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose.
key Exclusion Criteria:
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Documented medical history or ongoing gastrointestinal disease or other malabsorption that may affect the absorption of oral study drug.
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Participated in other clinical trials of investigational drugs or investigational devices within 28 days before the first medication; or received chemotherapy, targeted therapy, immunotherapy and clinical trial medication and other anti-tumor treatment within 4 days or 5 half-lives of the first medication (whichever is shorter), or received radiotherapy, endocrine drugs or Chinese patent medicines with anti-tumor indications 2 weeks before the first medication;
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The toxicity of previous anti-tumor treatment has not recovered to grade 0 or 1 (alopecia, chemotherapy-induced peripheral neurotoxicity ≤ grade 2 can be included).
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Major surgical surgery (except biopsy) or incomplete healing of the surgical incision 4 times before the first study drug treatment;
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Known other malignant tumors within 2 years before enrollment (except treated basal cell carcinoma, scaly cell carcinoma and/or radical carcinoma in situ);
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meningeal metastasis confirmed by MRI or cerebrospinal fluid cytology, increased intracranial pressure or unstable central nervous symptoms of brain metastasis (need to use any intracranial antihypertensive agents, glucocorticoids or anticonvulsant drugs within 2 weeks before the first dose);
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Previous history of interstitial lung disease, drug-induced interstitial lung disease, symptomatic interstitial lung disease or any evidence of active pneumonia on chest CT scan 4 before the first study drug treatment;
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known to interfere with the test requirements of mental illness or drug abuse disease.
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History of human immunodeficiency virus HIV infection, or active bacterial or fungal infection requiring systemic treatment 14.
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presence of active syphilis infection.
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Subjects with known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection with abnormal liver function.
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History of clinically significant cardiovascular disease.
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History of serious allergic reactions to the study drugs or excipients used in the protocol.
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Women who are pregnant or lactating.
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Prior use of SERD oral medications.
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Subjects who use drugs or herbal supplements known to be moderate/strong inhibitors of CYP3A 2. Subjects who use drugs or herbal supplements known to be moderate/strong inducers of CYP3A 4 weeks before the first dose.
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Other conditions that the investigator considers unsuitable for this study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Fudan University Shanghai Cancer Center | Shanghai | Shanghai | China |
Sponsors and Collaborators
- Jiangsu Simcere Pharmaceutical Co., Ltd.
Investigators
- Principal Investigator: Jiong Wu, phD, chief physician
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SIM-1907-02-SERD-101