計劃書編號BH-30643-01
試驗執行中
2025-06-15 - 2028-03-31
Phase I/II
召募中3
ICD-10C33
氣管惡性腫瘤
ICD-10Z51.12
來院接受抗腫瘤免疫療法
ICD-9162.0
氣管惡性腫瘤
一項針對罹患帶有EGFR和/或HER2突變之局部晚期或轉移性NSCLC的成年受試者，評估BH-30643之安全性、耐受性、藥物動力學及抗腫瘤活 性的第1/2期開放性、多中心、首次用於人體試驗(SOLARA)
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試驗申請者
保瑞爾生技股份有限公司
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試驗委託 / 贊助單位名稱
保瑞爾生技股份有限公司
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臨床試驗規模
多國多中心
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更新日期
2026/03/01
試驗主持人及試驗醫院
實際收案人數
0 召募中
適應症
帶有表皮生長因子受體 (EGFR) 和/或人類表皮生長因子受體 2 (HER2) 突變的局部晚期或轉移性非小細胞肺癌 (NSCLC)
試驗目的
Primary Objective :
Phase 1, Part 1 (Dose Escalation)
•To evaluate the safety and tolerability of BH-30643 at increasing dose levels in adult participants with locally advanced or metastatic NSCLC harboring EGFR and/or HER2 mutations.
•To determine the dose-limiting toxicities (DLTs) of BH-30643 in adult participants with locally advanced or metastatic NSCLC harboring EGFR and/or HER2 mutations and the maximum tolerated dose (MTD), if applicable.
•To identify the recommended doses for expansion (RDEs).
Phase 1, Part 2 (Dose Expansion/Optimization)
•To evaluate the safety, tolerability, and preliminary antitumor activity of BH-30643 at selected RDEs to determine the recommended Phase 2 dose (RP2D).
Phase 2
•To determine the antitumor activity of BH-30643 by response rate in selected populations of adult participants with locally advanced or metastatic NSCLC harboring EGFR and/or HER2 mutations at the RP2D.
Secondary Objectives :
Phase 1
•To characterize the single- and multiple-dose pharmacokinetic (PK) properties of BH-30643.
•To characterize the preliminary antitumor activity of BH-30643 in adult participants with locally advanced or metastatic NSCLC harboring EGFR and/or HER2 mutations.
Phase 2
•To further characterize the antitumor activity of BH-30643 at the RP2D.
•To confirm the safety and tolerability of BH-30643 at the RP2D.
•To assess the population PK (PopPK) of BH+30643 and to explore correlations between PK, response, and/or safety findings in participants with locally advanced or metastatic NSCLC harboring EGFR and/or HER2 mutations.
•To estimate the effect of BH-30643 on patient reported outcomes (PROs): global health status/Quality of Life (QoL) using the European Organization for Research and Treatment QoL Questionnaire (EORTC QLQ-C30), and the NSCLC Symptom Assessment Questionnaire (NSCLC SAQ).
藥品名稱
膠囊劑
膠囊劑
膠囊劑
主成份
BH-30643
劑型
130
130
130
劑量
10mg/capsule
40mg/capsule
40mg/capsule
評估指標
主要評估指標：
第 1 期
•DLT 發生率（僅限第 1 部分，劑量遞增）。
•不良事件 (AE) 的發生率，依照類型、頻率、嚴重程度（依據美國國家癌症研究院 [NCI] 不良事件通用術語標準 [CTCAE] 第 5.0 版分級）、嚴重性及與試驗藥物的關係進行整體特性描述。
第 2 期
•在選定受試者族群中，由盲性獨立中央審查委員會 (BICR) 依據實體腫瘤反應評估標準 (RECIST) 第 1.1 版判定之客觀反應率 (ORR)。
第 1 期
•DLT 發生率（僅限第 1 部分，劑量遞增）。
•不良事件 (AE) 的發生率，依照類型、頻率、嚴重程度（依據美國國家癌症研究院 [NCI] 不良事件通用術語標準 [CTCAE] 第 5.0 版分級）、嚴重性及與試驗藥物的關係進行整體特性描述。
第 2 期
•在選定受試者族群中，由盲性獨立中央審查委員會 (BICR) 依據實體腫瘤反應評估標準 (RECIST) 第 1.1 版判定之客觀反應率 (ORR)。
主要納入條件
To be eligible for the study, subject must meet all of the following inclusion criteria:
1.Ability to understand and willingness to sign a written ICF, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC), prior to the initiation of any screening or study-specific procedures.
2.Pathologically confirmed diagnosis of locally advanced or metastatic NSCLC, not amenable to curative definitive therapy, harboring EGFR and/or HER2 tyrosine KD mutations in exon 18, 19, 20, or 21, tested by a pre-qualified local or central NGS, quantitative polymerase chain reaction (qPCR), or other assay performed in a Clinical Laboratory Improvement Amendments-certified laboratory in the US or an equivalently accredited laboratory outside of the US. Refer to the EGFR classical, atypical, and ex20ins mutations and the HER2 mutations described in the Study Background. Further detailed requirements for Phase 1 and Phase 2 cohorts are described as follows:
Phase 1, Part 1 (Dose Escalation, including the Backfill Cohorts)
Participants should have received approved and available EGFR/HER2 targeted therapies or other standard therapies prior to enrolling in Phase 1. Participants without prior EGFR-TKI or HER2 targeted therapy may be enrolled in the Backfill cohorts, if they are deemed ineligible for available standard therapy, as assessed by the PI; the reason for ineligibility needs to be documented in their medical record and on the electronic case report forms.
Prior Therapy Requirements for Phase 1, Part 1:
•Disease progression on or intolerance to relevant available approved standard therapies (such as target therapies, chemotherapy, etc.), or ineligible to such therapies, judged by the PI, with documented reason for the ineligibility.
•Systemic anti-Vascular Endothelial Growth Factor Receptor inhibitor or immunotherapy are allowed.
•No limit on prior lines and prior therapies.
•Participants must be fully informed of any targeted or other therapies with clinical benefit they may be forgoing by enrolling in this study.
Phase 1, Part 2 (Dose Expansion)
Prior Therapy Requirements for Phase 1, Part 2: Note: For all Dose Expansion cohorts, prior treatment with investigational therapies targeting EGFR and/or HER2 is not permitted.
•Cohort a. (EGFR classical mutation): Participants have been previously treated with a third generation EGFR TKI. Must have documented on-target EGFR TKI resistance mutation(s) detected after progression on the most recent systemic therapy. No more than 3 total prior lines of therapies.
•Cohort b. (EGFR atypical mutation): Participants have been previously treated with one EGFR-TKI; any additional lines of non-EGFR TKI therapy allowed.
•Cohort c. (EGFR exon20 insertion): Participants have been previously treated with no more than 2 total prior lines of therapies.
•Cohort d. (HER2 mutation): Participants have been previously treated with no more than 2 total prior lines of therapies. Participants must not have received a prior HER2 TKI OR must have a documented HER2 TKI resistance mutation detected.
•Cohort e. Participants with EGFR classical mutation and had no prior EGFR TKI treatment including EGFR-TKI as adjuvant therapy.
•Cohort f. Participants with EGFR atypical mutation and had no prior EGFR TKI treatment.
Phase 2
EGFR or HER2 mutations determined by local tests that are not approved by the FDA or Regulatory Authority(ies) outside of the US need to be prospectively confirmed by a central, Sponsor-selected, NGS test for determination of molecular eligibility. However, local tests that are approved by the FDA or Regulatory Authority(ies) outside of the US can be used directly without prospective central confirmation to determine molecular eligibility. Participants directly enrolled by local testing will be retrospectively tested by the central, Sponsor-selected, NGS test. All local tests need to use samples collected during or after disease progression while on the most recent prior treatment or at diagnosis (if no prior line of EGFR or HER2 targeted treatment). The Sponsor selected central NGS test will use blood samples collected at Screening. The detailed requirements for Phase 2 cohorts will be defined in a future protocol amendment pending the outcome of the Phase 1 investigation. Phase 2 will enroll participants with locally advanced or metastatic NSCLC based on the following mutation types:
•EGFR classical mutation (ex19del or L858R)
•EGFR atypical mutation
•EGFR ex20ins mutation
•HER2 mutation
3.Adults age ≥ 18 years old (or as required by local regulation).
4.Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 1.
5.Has a life expectancy of ≥ 3 months.
6.Must have at least 1 measurable target extracranial lesion according to RECIST v1.1 (Appendix 1).
7.Participants with asymptomatic brain metastases (treated or untreated) are eligible to enroll if they satisfy the following criteria:
•Requirement of steroids at a stable or decreasing dose (≤ 12 mg/day dexamethasone or equivalent) for at least 14 days prior to study entry.
•Participants on stable doses of anti-seizure medication (same dose for 14 days prior to study entry); moderate and/or strong CYP3A4 inducers are prohibited. See Section 6.7 for a guidance on acceptable concomitant medications.
•A minimum of 14 days must have elapsed from the completion of whole brain radiation treatment (WBRT) before the start of treatment with the study drug, and all side effects (with the exception of alopecia) from WBRT are resolved to Grade ≤ 1.
•A minimum of 7 days must have elapsed from the completion of stereotactic radiosurgery to the brain before the start of treatment with the study drug and all AEs (with the exception of alopecia or other non-clinically significant events) from stereotactic radiosurgery are resolved to Grade ≤ 1.
8.Has adequate organ function defined as follows:
•Hematologic: ANC > 1.5 × 109 cells/L (without growth factor support for 2 weeks prior to testing); platelet count ≥ 100 × 109 cells/L (without transfusion or growth factor support for 1 week prior to testing); hemoglobin > 9.0 g/dL (without transfusion or growth factor support for 1 week prior to testing).
•Hepatic: Transaminase levels (AST/ALT) ≤ 2.5 × ULN. In cases of liver metastases, AST and ALT ≤ 5.0 × ULN; total bilirubin ≤ 1.5 × ULN in the absence of documented Gilbert's disease; and alkaline phosphatase ≤ 2.5 × ULN (≤ 5 × ULN in case of bone metastasis) are acceptable.
•Renal: Measured or estimated glomerular filtration rate ≥ 60 mL/min (using the Chronic Kidney Disease Epidemiology Collaboration formula).
9.Ability to swallow oral medications.
10.Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to the start of therapy and are not intending to become pregnant during study participation. Participants with reproductive potential are defined as one who is biologically capable of becoming pregnant unless they have undergone permanent sterilization or have premature menopause. WOCBP as well as fertile men and their partners must agree to abstain from sexual intercourse or use an effective form of contraception during the study and for 7-months (female participants) and 90 days (male participants and their female partner[s]) following the last dose of study drug. Female and male participants must also agree not to donate eggs or sperm until at least 7-months and 90 days, respectively, after the last dose of study drug. Highly effective contraceptive methods are described in Appendix 2.
11.Participants agree not to participate in another interventional study while on treatment.
1.Ability to understand and willingness to sign a written ICF, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC), prior to the initiation of any screening or study-specific procedures.
2.Pathologically confirmed diagnosis of locally advanced or metastatic NSCLC, not amenable to curative definitive therapy, harboring EGFR and/or HER2 tyrosine KD mutations in exon 18, 19, 20, or 21, tested by a pre-qualified local or central NGS, quantitative polymerase chain reaction (qPCR), or other assay performed in a Clinical Laboratory Improvement Amendments-certified laboratory in the US or an equivalently accredited laboratory outside of the US. Refer to the EGFR classical, atypical, and ex20ins mutations and the HER2 mutations described in the Study Background. Further detailed requirements for Phase 1 and Phase 2 cohorts are described as follows:
Phase 1, Part 1 (Dose Escalation, including the Backfill Cohorts)
Participants should have received approved and available EGFR/HER2 targeted therapies or other standard therapies prior to enrolling in Phase 1. Participants without prior EGFR-TKI or HER2 targeted therapy may be enrolled in the Backfill cohorts, if they are deemed ineligible for available standard therapy, as assessed by the PI; the reason for ineligibility needs to be documented in their medical record and on the electronic case report forms.
Prior Therapy Requirements for Phase 1, Part 1:
•Disease progression on or intolerance to relevant available approved standard therapies (such as target therapies, chemotherapy, etc.), or ineligible to such therapies, judged by the PI, with documented reason for the ineligibility.
•Systemic anti-Vascular Endothelial Growth Factor Receptor inhibitor or immunotherapy are allowed.
•No limit on prior lines and prior therapies.
•Participants must be fully informed of any targeted or other therapies with clinical benefit they may be forgoing by enrolling in this study.
Phase 1, Part 2 (Dose Expansion)
Prior Therapy Requirements for Phase 1, Part 2: Note: For all Dose Expansion cohorts, prior treatment with investigational therapies targeting EGFR and/or HER2 is not permitted.
•Cohort a. (EGFR classical mutation): Participants have been previously treated with a third generation EGFR TKI. Must have documented on-target EGFR TKI resistance mutation(s) detected after progression on the most recent systemic therapy. No more than 3 total prior lines of therapies.
•Cohort b. (EGFR atypical mutation): Participants have been previously treated with one EGFR-TKI; any additional lines of non-EGFR TKI therapy allowed.
•Cohort c. (EGFR exon20 insertion): Participants have been previously treated with no more than 2 total prior lines of therapies.
•Cohort d. (HER2 mutation): Participants have been previously treated with no more than 2 total prior lines of therapies. Participants must not have received a prior HER2 TKI OR must have a documented HER2 TKI resistance mutation detected.
•Cohort e. Participants with EGFR classical mutation and had no prior EGFR TKI treatment including EGFR-TKI as adjuvant therapy.
•Cohort f. Participants with EGFR atypical mutation and had no prior EGFR TKI treatment.
Phase 2
EGFR or HER2 mutations determined by local tests that are not approved by the FDA or Regulatory Authority(ies) outside of the US need to be prospectively confirmed by a central, Sponsor-selected, NGS test for determination of molecular eligibility. However, local tests that are approved by the FDA or Regulatory Authority(ies) outside of the US can be used directly without prospective central confirmation to determine molecular eligibility. Participants directly enrolled by local testing will be retrospectively tested by the central, Sponsor-selected, NGS test. All local tests need to use samples collected during or after disease progression while on the most recent prior treatment or at diagnosis (if no prior line of EGFR or HER2 targeted treatment). The Sponsor selected central NGS test will use blood samples collected at Screening. The detailed requirements for Phase 2 cohorts will be defined in a future protocol amendment pending the outcome of the Phase 1 investigation. Phase 2 will enroll participants with locally advanced or metastatic NSCLC based on the following mutation types:
•EGFR classical mutation (ex19del or L858R)
•EGFR atypical mutation
•EGFR ex20ins mutation
•HER2 mutation
3.Adults age ≥ 18 years old (or as required by local regulation).
4.Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 1.
5.Has a life expectancy of ≥ 3 months.
6.Must have at least 1 measurable target extracranial lesion according to RECIST v1.1 (Appendix 1).
7.Participants with asymptomatic brain metastases (treated or untreated) are eligible to enroll if they satisfy the following criteria:
•Requirement of steroids at a stable or decreasing dose (≤ 12 mg/day dexamethasone or equivalent) for at least 14 days prior to study entry.
•Participants on stable doses of anti-seizure medication (same dose for 14 days prior to study entry); moderate and/or strong CYP3A4 inducers are prohibited. See Section 6.7 for a guidance on acceptable concomitant medications.
•A minimum of 14 days must have elapsed from the completion of whole brain radiation treatment (WBRT) before the start of treatment with the study drug, and all side effects (with the exception of alopecia) from WBRT are resolved to Grade ≤ 1.
•A minimum of 7 days must have elapsed from the completion of stereotactic radiosurgery to the brain before the start of treatment with the study drug and all AEs (with the exception of alopecia or other non-clinically significant events) from stereotactic radiosurgery are resolved to Grade ≤ 1.
8.Has adequate organ function defined as follows:
•Hematologic: ANC > 1.5 × 109 cells/L (without growth factor support for 2 weeks prior to testing); platelet count ≥ 100 × 109 cells/L (without transfusion or growth factor support for 1 week prior to testing); hemoglobin > 9.0 g/dL (without transfusion or growth factor support for 1 week prior to testing).
•Hepatic: Transaminase levels (AST/ALT) ≤ 2.5 × ULN. In cases of liver metastases, AST and ALT ≤ 5.0 × ULN; total bilirubin ≤ 1.5 × ULN in the absence of documented Gilbert's disease; and alkaline phosphatase ≤ 2.5 × ULN (≤ 5 × ULN in case of bone metastasis) are acceptable.
•Renal: Measured or estimated glomerular filtration rate ≥ 60 mL/min (using the Chronic Kidney Disease Epidemiology Collaboration formula).
9.Ability to swallow oral medications.
10.Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to the start of therapy and are not intending to become pregnant during study participation. Participants with reproductive potential are defined as one who is biologically capable of becoming pregnant unless they have undergone permanent sterilization or have premature menopause. WOCBP as well as fertile men and their partners must agree to abstain from sexual intercourse or use an effective form of contraception during the study and for 7-months (female participants) and 90 days (male participants and their female partner[s]) following the last dose of study drug. Female and male participants must also agree not to donate eggs or sperm until at least 7-months and 90 days, respectively, after the last dose of study drug. Highly effective contraceptive methods are described in Appendix 2.
11.Participants agree not to participate in another interventional study while on treatment.
主要排除條件
If subject is fulfilling any of the following exclusion criteria, subject will not be able to join the study:
1.History of any concurrent malignancy within the previous 2 years with exception of adequately treated local basal cell or squamous carcinoma of the skin, in situ cervical cancer, adequately treated papillary noninvasive bladder cancer, or other adequately treated cancers in complete remission for ≥ 2 years at Screening. Participants receiving hormonal therapies for prostate or breast cancer with no evidence of disease are allowed.
2.Known other oncogenic driver alterations (eg, moderate or high MET amplification, oncogenic fusions or mutations, oncogenic RAF/RAS mutations, etc.). Concurrent EGFR and/or HER2 amplifications are permitted.
3.Known histological transformation (eg, to squamous cell carcinoma and small cell carcinoma).
4.Major surgery (excluding placement of vascular access or pleurex catheter or same day outpatient surgical procedure) within 4 weeks of the first dose of the study treatment.
5.Any clinically significant cardiovascular event within 6 months prior to study entry: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (New York Heart Association Classification Class ≥ II), life-threatening uncontrolled arrhythmia, cerebrovascular accident, or transient ischemic attack; or history of congenital prolonged QT syndrome or repeated demonstration of QTc interval > 470 milliseconds; or left ventricular ejection fraction (LVEF) < 40% by ECHO or MUGA.
6.Failure to recover from toxicity of prior anti-cancer therapy to baseline or Grade 1 severity (except for alopecia) per the NCI CTCAE v5.0. Participants with other residual greater than Grade 1 toxicity may be eligible with approval of the Sponsor’s Medical Monitor. Participants with treatable conditions such as hypothyroidism or hypertension may also be enrolled if the condition is well controlled.
7.Participants with any active uncontrolled infection.
8.Has active hepatitis B (Hep B) defined as Hep B viral load > 500 IU/mL (treated or untreated). Hep B viral load ≤ 500 IU/mL is not required to be treated if this is a local treatment guideline. Participants with untreated Hep B with viral load > 500 IU/mL can undergo treatment and be re screened and be eligible if subsequent Hep B viral load is ≤ 500 IU/mL. Participants with adequately treated Hep B with viral load > 500 IU/mL are not eligible.
9.Known active hepatitis C infection (Hep C Ab positive and quantitative hepatitis C virus (HCV) RNA greater than the lower limits of detection of the assay).
10.Known to be positive for human immunodeficiency virus (HIV) with any of the following:
•Not currently receiving highly active anti-retroviral therapy (HAART) or unwilling to continue HAART while on study treatment.
•Change in HAART within 6 months.
•Receiving any therapy that may interfere with study treatment.
•CD4 count < 350 cells per μL.
•History of opportunistic infection within 6 months.
11.Has received systemic chemotherapy, small molecule targeted therapy, or non-brain radiotherapy < 14 days prior to the first day of study drug administration; or immunotherapy or other large molecules < 28 days prior to the first day of study drug administration. Exception to Exclusion Criterion No. 11: Having received other EGFR or HER2 TKIs ≥ 7 days prior to the first dose of study drug is acceptable.
12.Has leptomeningeal disease, or spinal cord compression not definitively treated with surgery or radiation, or active symptomatic brain metastases.
13.Has uncontrolled tumor related pain. Symptomatic lesions amenable to palliative radiotherapy should be treated at least 14 days prior to the study drug administration.
14.Active or history of interstitial lung disease from any cause.
15.Pregnant, planning to become pregnant, or breastfeeding.
16.Treatment with any of the following concomitant drugs. Any of the following concomitant drugs, which are necessary for participant care, may be allowed after discussion with the Sponsor’s Medical Monitor:
•Strong and moderate inhibitors and inducers of cytochrome P450 (CYP)3A4 within 10 days or 5 half lives (whichever is shorter) of study drug initiation. Strong and moderate inhibitors and inducers of CYP3A4 are listed in Appendix 3.
•CYP3A4/5 substrates with narrow therapeutic indices. Drugs that are substrates of CYP3A4/5 are listed in Appendix 4.
•UDP-glucuronosyltransferase 1A1 (UGT1A1) inhibitors and substrates (see Appendix 5):
Moderate and/or strong UGT1A1 inhibitors.
UGT1A1 substrates with narrow therapeutic indices.
UGT1A1 substrates that are predominately metabolized by UGT1A1 and may cause increased bilirubin level when co-administered with strong UGT1A1 inhibitors.
•Inhibitors and substrates of organic anion transporting polypeptide (OATP)1B1 (eg, statins) are prohibited (see Appendix 6).
•Inhibitors of P-glycoprotein (P-gp) or substrates with narrow therapeutic indices of P gp, BCRP, and multidrug and toxin extrusion 2 (MATE2-K) are prohibited (see Appendix 7).
17.Current or anticipated treatment with concomitant drugs that are known to prolong the QT interval as listed in Appendix 8.
18.Malabsorption syndrome, any condition that would interfere with enteral absorption, or any other uncontrolled gastrointestinal disorder.
19.Significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular, or pulmonary disease, or any other condition that in the opinion of the PI or the Sponsor’s Medical Monitor may increase the risk associated with study participation, may interfere with the interpretation of the study results, or would make the participant inappropriate for entry into the study.
1.History of any concurrent malignancy within the previous 2 years with exception of adequately treated local basal cell or squamous carcinoma of the skin, in situ cervical cancer, adequately treated papillary noninvasive bladder cancer, or other adequately treated cancers in complete remission for ≥ 2 years at Screening. Participants receiving hormonal therapies for prostate or breast cancer with no evidence of disease are allowed.
2.Known other oncogenic driver alterations (eg, moderate or high MET amplification, oncogenic fusions or mutations, oncogenic RAF/RAS mutations, etc.). Concurrent EGFR and/or HER2 amplifications are permitted.
3.Known histological transformation (eg, to squamous cell carcinoma and small cell carcinoma).
4.Major surgery (excluding placement of vascular access or pleurex catheter or same day outpatient surgical procedure) within 4 weeks of the first dose of the study treatment.
5.Any clinically significant cardiovascular event within 6 months prior to study entry: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (New York Heart Association Classification Class ≥ II), life-threatening uncontrolled arrhythmia, cerebrovascular accident, or transient ischemic attack; or history of congenital prolonged QT syndrome or repeated demonstration of QTc interval > 470 milliseconds; or left ventricular ejection fraction (LVEF) < 40% by ECHO or MUGA.
6.Failure to recover from toxicity of prior anti-cancer therapy to baseline or Grade 1 severity (except for alopecia) per the NCI CTCAE v5.0. Participants with other residual greater than Grade 1 toxicity may be eligible with approval of the Sponsor’s Medical Monitor. Participants with treatable conditions such as hypothyroidism or hypertension may also be enrolled if the condition is well controlled.
7.Participants with any active uncontrolled infection.
8.Has active hepatitis B (Hep B) defined as Hep B viral load > 500 IU/mL (treated or untreated). Hep B viral load ≤ 500 IU/mL is not required to be treated if this is a local treatment guideline. Participants with untreated Hep B with viral load > 500 IU/mL can undergo treatment and be re screened and be eligible if subsequent Hep B viral load is ≤ 500 IU/mL. Participants with adequately treated Hep B with viral load > 500 IU/mL are not eligible.
9.Known active hepatitis C infection (Hep C Ab positive and quantitative hepatitis C virus (HCV) RNA greater than the lower limits of detection of the assay).
10.Known to be positive for human immunodeficiency virus (HIV) with any of the following:
•Not currently receiving highly active anti-retroviral therapy (HAART) or unwilling to continue HAART while on study treatment.
•Change in HAART within 6 months.
•Receiving any therapy that may interfere with study treatment.
•CD4 count < 350 cells per μL.
•History of opportunistic infection within 6 months.
11.Has received systemic chemotherapy, small molecule targeted therapy, or non-brain radiotherapy < 14 days prior to the first day of study drug administration; or immunotherapy or other large molecules < 28 days prior to the first day of study drug administration. Exception to Exclusion Criterion No. 11: Having received other EGFR or HER2 TKIs ≥ 7 days prior to the first dose of study drug is acceptable.
12.Has leptomeningeal disease, or spinal cord compression not definitively treated with surgery or radiation, or active symptomatic brain metastases.
13.Has uncontrolled tumor related pain. Symptomatic lesions amenable to palliative radiotherapy should be treated at least 14 days prior to the study drug administration.
14.Active or history of interstitial lung disease from any cause.
15.Pregnant, planning to become pregnant, or breastfeeding.
16.Treatment with any of the following concomitant drugs. Any of the following concomitant drugs, which are necessary for participant care, may be allowed after discussion with the Sponsor’s Medical Monitor:
•Strong and moderate inhibitors and inducers of cytochrome P450 (CYP)3A4 within 10 days or 5 half lives (whichever is shorter) of study drug initiation. Strong and moderate inhibitors and inducers of CYP3A4 are listed in Appendix 3.
•CYP3A4/5 substrates with narrow therapeutic indices. Drugs that are substrates of CYP3A4/5 are listed in Appendix 4.
•UDP-glucuronosyltransferase 1A1 (UGT1A1) inhibitors and substrates (see Appendix 5):
Moderate and/or strong UGT1A1 inhibitors.
UGT1A1 substrates with narrow therapeutic indices.
UGT1A1 substrates that are predominately metabolized by UGT1A1 and may cause increased bilirubin level when co-administered with strong UGT1A1 inhibitors.
•Inhibitors and substrates of organic anion transporting polypeptide (OATP)1B1 (eg, statins) are prohibited (see Appendix 6).
•Inhibitors of P-glycoprotein (P-gp) or substrates with narrow therapeutic indices of P gp, BCRP, and multidrug and toxin extrusion 2 (MATE2-K) are prohibited (see Appendix 7).
17.Current or anticipated treatment with concomitant drugs that are known to prolong the QT interval as listed in Appendix 8.
18.Malabsorption syndrome, any condition that would interfere with enteral absorption, or any other uncontrolled gastrointestinal disorder.
19.Significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular, or pulmonary disease, or any other condition that in the opinion of the PI or the Sponsor’s Medical Monitor may increase the risk associated with study participation, may interfere with the interpretation of the study results, or would make the participant inappropriate for entry into the study.
試驗計畫預計收納受試者人數
-
台灣人數
50 人
-
全球人數
420 人
