A Study of BPI-1178 in Patients With Advanced Solid Tumor and HR+/HER2- Breast Cancer

NCT04282031 | Recruiting Phase 1

• 1 other identifier: BPI-1178-2019-001
• Study Type: interventional
• Target: 224
• Locations: 1 country
• Sites: 1

Brief Summary

BPI-1178 is a novel, orally administered inhibitor of both cyclin-dependent kinase 4（CDK4）and CDK6 kinase activity. This Phase I study is a first-in-human (FIH) clinical trial designed to evaluate the safety, tolerability, and pharmacokinetic (PK) profile of oral BPI-1178 in patients with advanced solid tumors. The Phase IIa trial is designed to investigate the anti-tumor activity and safety of BPI-1178 in combination with endocrine therapy in patients with HR+/HER2-advanced breast cancer and to determine the dosing regimen for combination with endocrine therapy in a later confirmatory study.

Conditions

Advanced Solid Tumor; HR+/HER2- Breast Cancer

Outcome Measures

Primary Outcomes (3)

• phase 1 and 2a: Number of subjects with dose limiting toxicity (DLT)

  Up to Day 28 of Cycle 1 (28 days/cycle)

• phase 1: Maximum tolerated dose (MTD)

  Up to Day 28 in Cycle 1 (28 days/cycle)

• phase 2a: Objective response rate (ORR)

  Up to approximately 18 months

Secondary Outcomes (5)

• phase 1 and 2a: Number of subjects with adverse events

  Up to 30 days after the last dose of BPI-1178

• phase 1: Objective response rate (ORR)

  Up to approximately 18 months

• Phase 1 and 2a: Maximum plasma concentration (Cmax) of BPI-1178 and its main metabolites

  From single dosing in phase 1 or from baseline in phase 2a to the end of Cycle 1 (28 days/cycle)

• Phase 1 and 2a: Peak Plasma Time (Tmax) of BPI-1178 and its main metabolites

  From single dosing in phase 1 or from baseline in phase 2a to the end of Cycle 1 (28 days/cycle)

• Phase 1 and 2a: Area under the plasma concentration versus time curve (AUC) of BPI-1178 and its main metabolites

  From single dosing in phase 1 or from baseline in phase 2a to the end of Cycle 1 (28 days/cycle)

Other Outcomes (6)

• Clearance of BPI-1178 and its main metabolites

  From single dosing in phase 1 or from baseline in phase 2a to the end of Cycle 1 (28 days/cycle)

• Half life of BPI-1178 and its main metabolites

  From single dosing in phase 1 or from baseline in phase 2a to the end of Cycle 1 (28 days/cycle)

• Disease control rate ( DCR)

  Up to approximately 18 months

Study Arms (3)

phase 1 (dose escalation study, dose expansion study and PK trail)

EXPERIMENTAL

Participants will first receive single dose BPI-1178 orally at dose levels of 25mg, 75mg, 150mg, 250mg, 400mg and 500mg followed by a 7-day washout period , and then start receiving the 28 days/cycle continuous treatment until disease progression or unacceptable toxicity. After the 500 mg dose escalation trial is completed, the PK study will be conducted for the 400 mg dose group, the 300 mg dose group and the 200 mg dose group.

Drug: BPI-1178

phase 2a cohort A

EXPERIMENTAL

Participants will receive BPI-1178 at dose levels of MTD, MTD-1 or MTD-2 in combination with fulvestrant for 3 consecutive weeks, followed by 1 week drug withdrawal or continuous dosing for 28 days, in each 28-day treatment cycle, until disease progression or unacceptable toxicity.

Drug: BPI-1178; Drug: Fulvestrant

phase 2a cohort B

EXPERIMENTAL

Participants will receive BPI-1178 at dose levels of MTD, MTD-1 or MTD-2 in combination with letrozole for 3 consecutive weeks, followed by 1 week drug withdrawal or continuous dosing for 28 days, in each 28-day treatment cycle, until disease progression or unacceptable toxicity.

Drug: BPI-1178; Drug: Letrozole

Interventions

BPI-1178 DRUG

BPI-1178 once daily on Days 1 to 21 of a 28-day cycle

phase 1 (dose escalation study, dose expansion study and PK trail); phase 2a cohort A; phase 2a cohort B

Fulvestrant DRUG

Fulvestrant 500mg intramuscularly on Days 1 and 15 of Cycle 1, and on Day 1 of Cycle 2 and beyond

phase 2a cohort A

Letrozole DRUG

Letrozole 2.5 mg once daily of a 28-day cycle

phase 2a cohort B

Eligibility Criteria

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

You may qualify if:

• Have given written informed consent prior to any study specific procedures.
• Male or female, aged ≥18 years.
• Subjects with advanced solid tumors:
• Phase 1: Histologically or cytologically confirmed, locally advanced (not amenable to curative treatment of surgical resection or radiation therapy), recurrent, or metastatic solid tumors that were refractory to standard therapy or for which no standard-of-care therapy.
• Phase 2a Cohort A: HR+/HER2- locally advanced, recurrent, or metastatic breast cancer with disease progression after first-line endocrine therapy (not fulvestrant) or intolerant of it, histologically confirmed by the primary and/or metastatic lesions, not amenable to chemotherapy or curative treatment of surgical resection or radiation therapy; if the pathology of the primary and metastatic lesions are inconsistent, diagnosis should be based on metastatic lesions' pathology.
• Phase 2a Cohort B: HR+/HER2- locally advanced, recurrent, or metastatic breast cancer with no prior systemic therapy in this disease setting or relapse more than 1 years from completion of adjuvant endocrine therapy, histologically confirmed by the primary and/or metastatic lesions, not amenable to chemotherapy or curative treatment of surgical resection or radiation therapy; if the pathology of the primary and metastatic lesions are inconsistent, diagnosis should be based on metastatic lesions' pathology.
• Female patients with breast cancer at Phase IIa must also meet the following criteria:
• (1) Postmenopausal patients must meet at least one of the following criteria:
• Age ≥ 60 years old;
• Patients \< 60 years of age who have menstruation ceased for at least 12 consecutive months and have not received chemotherapy, tamoxifen, toremifene or ovarian function inhibitors, and have blood estrogen and FSH levels within the reference range for postmenopausal women;
• Previous bilateral ovariectomy;
• Patients \< 60 years of age who are being treated with tamoxifen or toremifene with blood estrogen and FSH levels within the reference range for postmenopausal women.
• (2) Premenopausal/perimenopausal patients must meet the following criteria: Premenopausal/perimenopausal patients requiring ovarian function suppression must start treatment at least 4 weeks prior to enrollment and the treatment should be maintained during the trial.
• At least 1 measurable lesion based on the RECIST v1.1 criteria.
• Life expectancy≥ 12 weeks.

You may not qualify if:

• Currently receiving or have received any CDK4/6 inhibitors.
• Have had allergies or history of severe allergies.
• Have participated in any clinical trials within 4 weeks prior to the dosing of BPI-1178.
• Have received anti-tumor therapy (including chemotherapy, endocrine therapy, targeted therapy, immunotherapy, tumor embolization, etc.; have received radiotherapy within 2 weeks before taking the investigational product) within 4 weeks before starting to take the investigational product \<except for premenopausal/perimenopausal patients with Gonadotropin-releasing hormone analogues \[GnRHa\] therapy allowed in Phase IIa study\>.
• Other malignancies present or previously present at the time of enrollment or still under treatment at the time of enrollment (only applicable to Phase IIa study)
• Any toxicity related to previous treatment before enrollment defined by CTCAE (v5.0) Grade≥2 (except hair loss).
• Presence of third interstitial fluid that cannot be controlled by drainage or other methods (such as large amounts of pleural fluid and ascites).
• Requiring long-term treatment of steroid.
• Having uncorrectable hypokalemia and hypomagnesemia at enrollment.
• Meet any of the following criteria: Various clinically significant heart rhythm and conduction abnormalities, such as atrial fibrillation, complete left bundle branch block, Level III conduction block, Level II conduction block, and PR interval \> 250 msec; Various factors that might increase risks of QT increased or arrhythmia events, e.g., symptomatic cardiac failure - New York Heart Association (NYHA) class 2-4, long QT syndrome congenital, Brugada syndrome, previous histories of QT increased (\> 470 ms for males, \> 480 ms for females) or TdP attack, first degree relative of the family with long QT syndrome or sudden death before 40 years' old with unexplained cause, and concomitant medication which may prolong QT interval; Suffering from following diseases within 6 months prior to administration of investigational product, including unstable angina pectoris, myocardial infarction, coronary heart disease, cerebrovascular accident or pulmonary embolism, or accepting cardiac revascularization.
• Known active infection, such as hepatitis B (HBV DNA ≥ 200 IU/mL), hepatitis C, human immunodeficiency virus (HIV) infection.
• Have a history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
• Based on the judgement of investigators, there might be multiple factors which could impact taking and absorption of BPI-1178, including gastrointestinal factors (e.g., obviously uncontrollable inflammatory gastrointestinal disorder, abdominal colostomy within 6 months or previous history of gastrointestinal perforation, extensive resection of small intestine and requirement of tube feeding or water/ nutritional supplement by parenteral route, inability to swallow, chronic diarrhoea and intestinal obstruction, etc.)
• Have spinal cord compression, metastases of the meninges, or brain metastases with obvious symptoms. The following cases of brain metastases without symptoms can be enrolled: brain metastases without obvious symptoms diagnosed at screening visit, steroids and/or local treatment not required judged by investigator; brain metastases without obvious symptoms after local treatment (such as radiotherapy), and steroids and/or antiepileptic therapy has stopped for at least 7 days before the first dosing of BPI-1178.
• In the judgment of the investigator, have a concomitant disease (such as severe hypertension, diabetes, thyroid disease, severe infection, portal hypertension, cirrhosis, etc.) that would endanger the subjects' safety or affect the completion of the study.

Sponsors & Collaborators

• Beta Pharma (Suzhou) Co., Ltd.: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Interventions

Fulvestrant; Letrozole

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Wenxiang Lu

CONTACT

+86-021-62165501; wenxiang.lu@betapharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2020
• First Posted: February 24, 2020
• Study Start: June 15, 2020
• Primary Completion: December 31, 2024
• Study Completion: June 30, 2025
• Last Updated: August 7, 2024

Record last verified: 2024-08

Locations

CN (1)