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)
-
試驗申請者
保瑞爾生技股份有限公司
-
試驗委託 / 贊助單位名稱
保瑞爾生技股份有限公司
-
臨床試驗規模
多國多中心
-
更新日期
2026/06/01
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 subjects with locally advanced or metastatic NSCLC harboring EGFR and/or HER2 mutations.
•To determine the dose-limiting toxicities (DLTs) of BH-30643 in adult subjects 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 efficacy of BH-30643 by response rate in selected populations of adult subjects 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 efficacy of BH-30643 in adult subjects 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 subjects 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 Informed Consent Form (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, documented in a molecular report of local NGS or qPCR testing in tumor tissue or blood samples taken 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). Prospective central testing using blood samples collected at Screening to determine EGFR or HER2 mutations will be permitted in Phase 2. Other local tests may be permitted after discussion with the Sponsor. All local tests must have been pre-qualified by the Sponsor and are performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory in the US or equivalently accredited diagnostic laboratory outside of the US. The detailed requirements for Phase 1 cohort are described as follows:
Phase 1
For Subjects with Classical or Atypical EGFR Mutations
•Disease progression on or intolerance to available approved EGFR TKI therapy, or for whom available EGFR TKI therapy is considered unsuitable or unlikely to improve disease outcome in the judgement of the PI.
•No limit on prior lines of EGFR TKI therapy.
•Additional lines of systemic chemotherapy or immunotherapy are allowed.
For Subjects with ex20ins EGFR Mutation
•Must have received systemic chemotherapy followed by amivantamab (if amivantamab is locally approved and available) or amivantamab in combination with chemotherapy.
•Additional lines of systemic therapy including kinase inhibitors, chemotherapy, or immunotherapy are allowed.
For Subjects with HER2 Mutation
•Must have received at least 1 line of systemic chemotherapy and HER2 targeted therapy (if locally approved and available).
•Additional lines of systemic therapy including kinase inhibitors, chemotherapy, or immunotherapy are allowed.
In Addition to meeting Phase 1 Dose Escalation Eligibility Criteria for Phase 1, Part 1 (Dose Escalation), additional inclusion criteria for Backfill and Phase 1, Part 2 (Dose Expansion/Optimization) Only:
•Subjects with EGFR mutations previously treated with an EGFR TKI must have either:
- A documented EGFR intrinsic (atypical or ex20ins) resistant mutation (eg, L858R +L718X) to the most recent EGFR TKI detected after disease progression
OR
- Acquired mutation conferring resistance (eg, T790M, C797S, or compound mutations) to the most recent EGFR TKI detected after disease progression by NGS testing or qPCR testing.
•Subjects with HER2 mutation must not have received a selective HER2 TKI (eg, BAY 2927088 and zongertinib) or have acquired resistance mutations after a selective HER2 TKI treatment (eg, T798X and C805X).
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.
7.Subjects 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.
•Subjects on stable doses of anti-seizure medication (same dose for 14 days prior to study entry).
•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 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 2 weeks 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 calculated creatinine clearance ≥ 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. Subjects 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 90 days (females and males) following the last dose of study drug. Subjects must also agree not to donate eggs or sperm until at least 90 days after the last dose of study drug.
11. Subjects agree not to participate in another interventional study while on treatment.
1.Ability to understand and willingness to sign a written Informed Consent Form (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, documented in a molecular report of local NGS or qPCR testing in tumor tissue or blood samples taken 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). Prospective central testing using blood samples collected at Screening to determine EGFR or HER2 mutations will be permitted in Phase 2. Other local tests may be permitted after discussion with the Sponsor. All local tests must have been pre-qualified by the Sponsor and are performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory in the US or equivalently accredited diagnostic laboratory outside of the US. The detailed requirements for Phase 1 cohort are described as follows:
Phase 1
For Subjects with Classical or Atypical EGFR Mutations
•Disease progression on or intolerance to available approved EGFR TKI therapy, or for whom available EGFR TKI therapy is considered unsuitable or unlikely to improve disease outcome in the judgement of the PI.
•No limit on prior lines of EGFR TKI therapy.
•Additional lines of systemic chemotherapy or immunotherapy are allowed.
For Subjects with ex20ins EGFR Mutation
•Must have received systemic chemotherapy followed by amivantamab (if amivantamab is locally approved and available) or amivantamab in combination with chemotherapy.
•Additional lines of systemic therapy including kinase inhibitors, chemotherapy, or immunotherapy are allowed.
For Subjects with HER2 Mutation
•Must have received at least 1 line of systemic chemotherapy and HER2 targeted therapy (if locally approved and available).
•Additional lines of systemic therapy including kinase inhibitors, chemotherapy, or immunotherapy are allowed.
In Addition to meeting Phase 1 Dose Escalation Eligibility Criteria for Phase 1, Part 1 (Dose Escalation), additional inclusion criteria for Backfill and Phase 1, Part 2 (Dose Expansion/Optimization) Only:
•Subjects with EGFR mutations previously treated with an EGFR TKI must have either:
- A documented EGFR intrinsic (atypical or ex20ins) resistant mutation (eg, L858R +L718X) to the most recent EGFR TKI detected after disease progression
OR
- Acquired mutation conferring resistance (eg, T790M, C797S, or compound mutations) to the most recent EGFR TKI detected after disease progression by NGS testing or qPCR testing.
•Subjects with HER2 mutation must not have received a selective HER2 TKI (eg, BAY 2927088 and zongertinib) or have acquired resistance mutations after a selective HER2 TKI treatment (eg, T798X and C805X).
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.
7.Subjects 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.
•Subjects on stable doses of anti-seizure medication (same dose for 14 days prior to study entry).
•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 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 2 weeks 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 calculated creatinine clearance ≥ 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. Subjects 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 90 days (females and males) following the last dose of study drug. Subjects must also agree not to donate eggs or sperm until at least 90 days after the last dose of study drug.
11. Subjects 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. Subjects 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). 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. Subjects with other residual Grade 1 toxicity may be eligible with approval of the Sponsor’s Medical Monitor. Subjects with treatable conditions such as hypothyroidism or hypertension may also be enrolled if the condition is well controlled.
7. Subjects 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. Subjects 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. Subjects 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 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 radiotherapy < 14 days prior to the first day of study drug administration; or immunotherapy < 28 days prior to the first day of study drug administration. Having received other EGFR or HER2 TKIs ≥ 7 days prior to the first dose of study drug is acceptable.
12. Has active symptomatic brain metastases, leptomeningeal disease, or spinal cord compression not definitively treated with surgery or radiation.
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. History of interstitial lung disease from any cause.
15. Actively receiving investigational therapy(ies) in another clinical study.
16. Pregnant, planning to become pregnant, or breastfeeding.
17. Treatment with any of the following concomitant drugs. Any of the following concomitant drugs, which are necessary for subject care, may be allowed after discussion with the Sponsor’s Medical Monitor:
•Strong inhibitors or inducers of cytochrome P450 (CYP)3A4 within 10 days or 5 half lives (whichever is shorter) of study drug initiation.
•CYP3A4/5 substrates with narrow therapeutic indices.
•Inhibitors of P-glycoprotein (P-gp) or substrates with narrow therapeutic indices of P-gp, BCRP, and organic anion transporting polypeptide (OATP)1B1/2B1 and MATE2-K are prohibited.
18.Current or anticipated treatment with concomitant drugs that are known to prolong the QT interval.
19. Malabsorption syndrome, any condition that would interfere with enteral absorption, or any other uncontrolled gastrointestinal disorder.
20. 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 subject 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. Subjects 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). 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. Subjects with other residual Grade 1 toxicity may be eligible with approval of the Sponsor’s Medical Monitor. Subjects with treatable conditions such as hypothyroidism or hypertension may also be enrolled if the condition is well controlled.
7. Subjects 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. Subjects 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. Subjects 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 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 radiotherapy < 14 days prior to the first day of study drug administration; or immunotherapy < 28 days prior to the first day of study drug administration. Having received other EGFR or HER2 TKIs ≥ 7 days prior to the first dose of study drug is acceptable.
12. Has active symptomatic brain metastases, leptomeningeal disease, or spinal cord compression not definitively treated with surgery or radiation.
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. History of interstitial lung disease from any cause.
15. Actively receiving investigational therapy(ies) in another clinical study.
16. Pregnant, planning to become pregnant, or breastfeeding.
17. Treatment with any of the following concomitant drugs. Any of the following concomitant drugs, which are necessary for subject care, may be allowed after discussion with the Sponsor’s Medical Monitor:
•Strong inhibitors or inducers of cytochrome P450 (CYP)3A4 within 10 days or 5 half lives (whichever is shorter) of study drug initiation.
•CYP3A4/5 substrates with narrow therapeutic indices.
•Inhibitors of P-glycoprotein (P-gp) or substrates with narrow therapeutic indices of P-gp, BCRP, and organic anion transporting polypeptide (OATP)1B1/2B1 and MATE2-K are prohibited.
18.Current or anticipated treatment with concomitant drugs that are known to prolong the QT interval.
19. Malabsorption syndrome, any condition that would interfere with enteral absorption, or any other uncontrolled gastrointestinal disorder.
20. 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 subject 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
