Non Small Cell Lung Cancer
Conditions
Keywords
HBI-8000, Pembrolizumab, NSCLC
Brief summary
A Phase 2 Study to Assess the Safety and Efficacy of HBI-8000 in Combination with Pembrolizumab for Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)
Detailed description
This Phase 2 study evaluates HBI-8000, a histone deacetylase inhibitor (HDACi) in combination with pembrolizumab for the treatment of patients with advanced or metastatic non-small cell lung cancer who possess programmed death ligand 1 (PD-L1) expression Tumor Proportion Score (TPS) of 1% or greater. The Treatment Phase allowed for up to 24 months of treatment (cycles were 21 days), providing the subject did not experience disease progression or unacceptable toxicity.
Interventions
DRUGHBI-8000 in combination with pembrolizumab
Participants will take 30 mg of HBI-8000 by mouth every 3-4 days on a twice weekly (BIW) schedule. Pembrolizumab will be administered at 400 mg IV every 6 weeks (Q6W) or 200 mg IV every 3 weeks (Q3W) according to Prescribing Information and institution's prescribing practice for pembrolizumab.
Sponsors
HUYABIO International, LLC.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adults at least 18 years of age. 2. Eastern Cooperative Oncology Group (ECOG) performance status ≤2. 3. Histopathologically confirmed diagnosis of NSCLC PD-L1 expression TPS ≥1% as determined by an FDA-approved test. 4. Have at least one measurable target lesion as defined by RECIST v.1.1. 5. Have not received immune checkpoint inhibitor therapy or more than one regimen of chemotherapy for advanced or metastatic disease. Subjects who have previously received immune checkpoint inhibitor therapy in the adjuvant or neoadjuvant setting may be allowed if disease progression occurred \>6 months after the last dose and no clinically significant immune related toxicities leading to treatment discontinuation were observed. 6. Prior adjuvant or neoadjuvant systemic therapy with chemotherapy, EGFR or ALK mutation directed therapy must have been completed \>4 weeks before Cycle 1 Day 1 (C1D1) dosing and recovered from all treatment related toxicity. 7. Any prior palliative radiotherapy or minor surgery must be completed at least 2 weeks and 1 week respectively before C1D1 dosing and recovered from all treatment related toxicities. 8. Adequate major organ functions at baseline as evidenced by laboratory findings within 14 days prior to C1D1 study drug administration as defined below: 1. White blood cells (WBC) ≥3000/μL, neutrophils ≥1500/μL, platelets ≥100×103/μL, hemoglobin ≥9.0 g/dL, independent of transfusion. 2. Serum creatinine ≤1.5 mg/dL, normal electrolytes, phosphorus, and calcium. 3. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × upper limit of normal (ULN), alkaline phosphatase ≤2.5 × ULN unless bone metastases present, bilirubin ≤1.5 × ULN (unless known Gilbert's disease where it must be ≤3 × ULN) and serum albumin ≥3.0 g/dL. 4. Thyroid stimulating hormone (TSH) within normal limits. 9. Life expectancy ≥12 weeks. 10. A negative serum pregnancy test at baseline for women of childbearing potential (WOCBP). 11. Women of childbearing potential. (WOCBP), non-surgically sterile or premenopausal female capable of becoming pregnant and men (due to potential risk of drug exposure through the ejaculate) must agree to use an acceptable method of contraception while enrolled on this study, and for a period of 5 months following the last dose of treatment. Acceptable methods of birth control in this trial include 2 highly effective methods of birth control (as determined by the Investigator; one of the methods must be a barrier technique) or abstinence. 12. Have the ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
1. History of Grade ≥3 hypersensitivity reactions to monoclonal antibodies. 2. History of a cardiovascular illness including: QT interval corrected by heart rate using Fridericia's correction formula (QTcF) \>450 ms in male or \>470 ms in female, congenital long QT syndrome, congestive heart failure (New York Heart Association Grade III or IV) (Protocol Appendix 2); unstable angina or myocardial infarction within the previous 6 months; or symptomatic cardiac arrhythmia despite medical management. 3. Uncontrolled hypertension, systolic blood pressure (SBP) \>160 mmHg or diastolic blood pressure (DBP) \>100 mmHg. 4. Central nervous system metastasis or leptomeningeal disease except when treatment for brain metastasis is completed \>14 days prior to C1D1 and stable for ≥4 weeks on \<10 mg daily prednisone or equivalent. 5. History of hemorrhagic diarrhea, inflammatory bowel disease, active uncontrolled peptic ulcer disease or bowel resection that affects absorption of orally administered drugs. 6. Recurrent pleural effusion requiring repetitive palliative thoracentesis within 3 months prior to study entry, except for subjects with a pleurex port. 7. Active, known, or suspected autoimmune disease, or history of immune-mediated toxicity leading to treatment discontinuation, except for type I diabetes mellitus, hypothyroidism only requiring hormone replacement or skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic therapy. 8. Active pneumonitis, history of non-infectious pneumonitis that required treatment with steroids, or history of interstitial lung disease. 9. Active uncontrolled bacterial, viral, or fungal infection requiring systemic therapy. 10. Known history of testing positive for human immunodeficiency virus (HIV), known acquired immunodeficiency syndrome (AIDS). 11. Active hepatitis B (hepatitis B surface antigen \[HBVsAg\] positive), or hepatitis C (HCV antibody test or serum hepatitis C ribonucleic acid \[RNA\] positive). 12. Received approved live vaccines within 30 days of planned C1D1. Inactivated viral vaccines or vaccines based on subviral component are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are not allowed. COVID-19 vaccination should be administered \>7 days before C1D1. 13. Any condition requiring chronic systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalents) or other immunosuppressive medications, or steroids use within 14 days of study drug administration. Inhaled or topical steroids are permitted. 14. Use of other investigational agent (drug not marketed for any indication) within 28 days or at least 5 half-lives (whichever is shorter) before study drug administration. 15. Pregnant or breast-feeding women. 16. Second malignancy unless in remission for 2 years; subjects with non-melanomatous skin cancer, carcinoma in situ of the cervix treated with curative intent, or curatively treated prostate cancer with prostate-specific antigen (PSA) \<2.0 ng/mL can be included. 17. Underlying medical conditions that, in the Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity determination or adverse events. 18. Unwilling or unable to comply with procedures required in this protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of HBI-8000 When Administered in Combination With Standard Dose and Regimen of Pembrolizumab | From the start of treatment until 30 days after the last dose of HBI-8000, up to approximately 13 months | Number of participants experiencing treatment-emergent adverse events (TEAEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 |
Countries
United States
Participant flow
Recruitment details
This was a multicenter (9 sites in the US: hospital, regional medical, and research centers), open label, Phase 2 study of HBI 8000 in combination with an approved dose of pembrolizumab as a first line checkpoint inhibitor therapy for advanced or metastatic non-small cell lung cancer (NSCLC). Recruitment was from 15Feb 2022 to 01Sep2022. In December 2022, enrollment was suspended.
Pre-assignment details
Subjects had to satisfy screening criteria prior to treatment with HBI-8000 + Pembrolizumab. The screening period could be up to 28 days and was comprised of assessing medical history, concomitant therapies, clinical laboratory testing, and other clinical assessments to document the subject met all inclusion criteria and none of the exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| HBI-8000 in Combination With Pembrolizumab HBI-8000 in combination with pembrolizumab: Participants will take 30 mg of HBI-8000 by mouth every 3-4 days on a twice weekly (BIW) schedule. Pembrolizumab was administered at 400 mg IV every 6 weeks (Q6W) or 200 mg IV every 3 weeks (Q3W) according to Prescribing Information and institution's prescribing practice for pembrolizumab. | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Lack of Efficacy | 2 |
Baseline characteristics
| Characteristic | HBI-8000 in Combination With Pembrolizumab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 5 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 5 |
| other Total, other adverse events | 5 / 5 |
| serious Total, serious adverse events | 3 / 5 |
Outcome results
Primary
Safety and Tolerability of HBI-8000 When Administered in Combination With Standard Dose and Regimen of Pembrolizumab
Number of participants experiencing treatment-emergent adverse events (TEAEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0
Time frame: From the start of treatment until 30 days after the last dose of HBI-8000, up to approximately 13 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HBI-8000 in Combination With Pembrolizumab | Safety and Tolerability of HBI-8000 When Administered in Combination With Standard Dose and Regimen of Pembrolizumab | Subjects experiencing TEAEs | 5 Participants |
| HBI-8000 in Combination With Pembrolizumab | Safety and Tolerability of HBI-8000 When Administered in Combination With Standard Dose and Regimen of Pembrolizumab | Subjects not experiencing TEAEs | 0 Participants |