Safety and Efficacy of Combining APL-101 With Frontline Osimertinib in Patients With EGFR-mutated Metastatic Non-small Cell Lung Cancer (NSCLC)

  • STATUS
    Recruiting
  • End date
    Nov 30, 2026
  • participants needed
    22
  • sponsor
    Washington University School of Medicine
Updated on 23 April 2022

Summary

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.

Details
Condition Metastatic Non Small Cell Lung Cancer
Treatment Osimertinib, APL-101
Clinical Study IdentifierNCT04743505
SponsorWashington University School of Medicine
Last Modified on23 April 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Histologically confirmed metastatic non-small cell lung cancer 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 12 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)

Exclusion Criteria

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
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
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