NCT04743505进行中（未招募）1 期
Phase I/II Study Exploring the Safety and Efficacy of Combining APL-101 With Frontline Osimertinib in Patients With EGFR-mutated Metastatic Non-small Cell Lung Cancer (NSCLC)
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Toxicity as measured by number of study treatment related adverse events (Phase I only)
研究概览
简要总结
In this study, patients with metastatic non-small cell lung cancer that is EGFR-mutated, who have received at least 8 and not more than 12 weeks of treatment with osimertinib without demonstrating disease progression, will receive APL-101 in combination with osimertinib until progression. Dosing of APL-101 will be escalated until the maximum tolerated dose is determined, at which point 10 additional patients will be enrolled at that dose in the expansion cohort.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed metastatic non-small cell lung cancer, or locally advanced disease that is not amendable for curative intent therapy, with TKI-sensitive EGFR mutation through CLIA certified lab.
- •Measurable disease by RECIST 1.1 with at least one lesion accessible for core biopsy.
- •Planning to initiate treatment with standard of care osimertinib 80 mg QD. In order to continue treatment with osimertinib + APL-101, patients must have received at least 8 and no more than 16 weeks of SOC osimertinib without disease progression.
- •At least 18 years of age.
- •ECOG performance status ≤ 1
- •Normal bone marrow and organ function as defined below:
- •Absolute neutrophil count ≥ 1,500/mcL
- •Platelets ≥ 100,000/mcL
- •Hemoglobin ≥ 9 g/dL (transfused Hgb allowed)
- •Total bilirubin ≤ 1.5 mg/dL or ≤ 26 µmol/L
- •AST(SGOT)/ALT(SGPT) ≤ 2.5 x institutional upper limit of normal (IULN) (≤ 5.0 x IULN if liver metastases)
- •Creatinine ≤2 x IULN or Creatinine clearance calculated by Cockcroft-Gault formula ≥60 ml/min
- •Serum calcium (after correcting for albumin level) ≤ IULN
- •Serum phosphorus ≤ IULN
- •The effects of APL-101 on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study and for the duration of the study.
- •Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
排除标准
- •Prior treatment with osimertinib in the metastatic setting (outside of osimertinib given immediately prior to and during the enrollment period). Prior treatment with chemotherapy in the neoadjuvant, adjuvant, or first-line metastatic setting is however allowed.
- •Prior immunotherapy and/or frontline EGFR-directed treatment in the metastatic setting. EGFR directed therapy in the adjuvant setting is permitted, as long as the disease-free interval between completion of adjuvant therapy with EGFR directed therapy and initiation of osimertinib is more than or equal to 1 year.
- •Disease refractory to osimertinib, given immediately prior to and during enrollment period.
- •A history of other malignancy with the exception of:
- •malignancies for which all treatment was completed at least 1 year before registration and the patient has no evidence of disease; or
- •known indolent malignancies, or malignancies that do not require active treatment and are unlikely not alter the course of treatment of metastatic NSCLC per treating physician.
- •Currently receiving any other investigational agents or herbal medications
- •Presence of symptomatic central nervous system metastases or neurologically unstable CNS symptoms (unable to taper steroids). Patients with treated brain metastases are eligible. Patients with asymptomatic brain metastases prior to initiation of osimertinib will be eligible to receive combination therapy as long as their disease is shown to be responsive to osimertinib.
- •A history of allergic reactions attributed to compounds of similar chemical or biologic composition to APL-101, osimertinib, or other agents used in the study.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, immune deficiencies, hepatitis B, untreated hepatitis C, uncontrolled diabetes, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infraction within the past 6 months, uncontrolled cardiac arrhythmia, or prolonged QTc interval > 450 ms.
- •Uncontrolled or symptomatic pleural or pericardial effusion. Effusion controlled by presence of an indwelling pleural catheter is not exclusionary.
- •Decompensated heart failure or heart failure with reduced ejection fraction (<50%)
- •Major surgery within 30 days prior to first day of study treatment (osimertinib + APL-101).
- •Poorly controlled diarrheal or gastrointestinal disorders (grade 2 or higher diarrhea, nausea, or vomiting at baseline).
- •Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
- •Unresolved grade 2 or higher treatment-related toxicities (with the exception of endocrine abnormalities as a result of immunotherapies that are being managed with hormonal supplementation). However, if the treating physician is under the impression that the toxicity under question is unlikely to affect study participation, patient eligibility can be discussed with the PI on a subject by subject basis. After enrollment to this study, osimertinib-related toxicities must resolve to ≤ grade 1 before patient may begin combination therapy.
- •Presence of interstitial lung disease
研究组 & 干预措施
Phase I Dose Level 1: APL-101 + Standard of Care Osimertinib
Experimental
- After 8-16 weeks of osimertinib, patients will be imaged as per standard of care. If imaging does not show disease progression, patients will continue on to study treatment with the combination of osimertinib and APL-101.
- APL-101 is an oral drug which will be administered on an outpatient basis at the assigned dose twice daily on Days 1 through 28 of each 28-day cycle
- Osimertinib is an oral drug which will be administered on an outpatient basis at a dose of 80 mg once daily on Days 1 through 28 of each 28-day cycle.
干预措施: APL-101 (Drug)
Phase I Dose Level 1: APL-101 + Standard of Care Osimertinib
Experimental
- After 8-16 weeks of osimertinib, patients will be imaged as per standard of care. If imaging does not show disease progression, patients will continue on to study treatment with the combination of osimertinib and APL-101.
- APL-101 is an oral drug which will be administered on an outpatient basis at the assigned dose twice daily on Days 1 through 28 of each 28-day cycle
- Osimertinib is an oral drug which will be administered on an outpatient basis at a dose of 80 mg once daily on Days 1 through 28 of each 28-day cycle.
干预措施: Osimertinib (Drug)
Phase I Dose Level 2: APL-101 + Standard of Care Osimertinib
Experimental
- After 8-16 weeks of osimertinib, patients will be imaged as per standard of care. If imaging does not show disease progression, patients will continue on to study treatment with the combination of osimertinib and APL-101.
- APL-101 is an oral drug which will be administered on an outpatient basis at the assigned dose twice daily on Days 1 through 28 of each 28-day cycle
- Osimertinib is an oral drug which will be administered on an outpatient basis at a dose of 80 mg once daily on Days 1 through 28 of each 28-day cycle.
干预措施: APL-101 (Drug)
Phase I Dose Level 2: APL-101 + Standard of Care Osimertinib
Experimental
- After 8-16 weeks of osimertinib, patients will be imaged as per standard of care. If imaging does not show disease progression, patients will continue on to study treatment with the combination of osimertinib and APL-101.
- APL-101 is an oral drug which will be administered on an outpatient basis at the assigned dose twice daily on Days 1 through 28 of each 28-day cycle
- Osimertinib is an oral drug which will be administered on an outpatient basis at a dose of 80 mg once daily on Days 1 through 28 of each 28-day cycle.
干预措施: Osimertinib (Drug)
Phase II: APL-101 + Standard of Care Osimertinib
Experimental
- After 8-16 weeks of osimertinib, patients will be imaged as per standard of care. If imaging does not show disease progression, patients will continue on to study treatment with the combination of osimertinib and APL-101.
- APL-101 is an oral drug which will be administered on an outpatient basis at the assigned dose (this dose will be determined in Phase I of the study) twice daily on Days 1 through 28 of each 28-day cycle
- Osimertinib is an oral drug which will be administered on an outpatient basis at a dose of 80 mg once daily on Days 1 through 28 of each 28-day cycle.
干预措施: APL-101 (Drug)
Phase II: APL-101 + Standard of Care Osimertinib
Experimental
- After 8-16 weeks of osimertinib, patients will be imaged as per standard of care. If imaging does not show disease progression, patients will continue on to study treatment with the combination of osimertinib and APL-101.
- APL-101 is an oral drug which will be administered on an outpatient basis at the assigned dose (this dose will be determined in Phase I of the study) twice daily on Days 1 through 28 of each 28-day cycle
- Osimertinib is an oral drug which will be administered on an outpatient basis at a dose of 80 mg once daily on Days 1 through 28 of each 28-day cycle.
干预措施: Osimertinib (Drug)
结局指标
主要结局
Toxicity as measured by number of study treatment related adverse events (Phase I only)
时间窗: Through 30 days after last dose of treatment (estimated to be 21 months)
-Toxicity is measured by CTCAE v 5.0
Toxicity as measured by number of study discontinuations due to treatment-related adverse events (Phase I only)
时间窗: Through 30 days after last dose of treatment (estimated to be 21 months)
-Toxicity is measured by CTCAE v 5.0
Progression-free survival (PFS) (Phase II or received MTD only)
时间窗: At 1 year
* PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Patients who neither progress nor die by the data cutoff date will be censored at the last follow up date. * Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.
次要结局
- Maximum tolerated dose of APL-101 (MTD) (Phase I only)(Through completion of cycle 1 (each cycle is 28 days) for all Phase I participants (estimated to be 19 months))
- Objective response rate as measured by the proportion of participants achieving a confirmed complete response or partial response (Phase II or received MTD only)(Through completion of treatment (estimated to be 20 months))
- Duration of response (DOR) (Phase II or received MTD only)(Through completion of treatment (estimated to be 20 months))
- Overall survival (OS) (Phase II or received MTD only)(Through 3 year follow-up (estimated to be 4 years and 8 months))
研究者
研究点 (1)
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