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

NCT04743505 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 202104039
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Metastatic Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (3)

• Toxicity as measured by number of study treatment related adverse events (Phase I only)

  -Toxicity is measured by CTCAE v 5.0

  Through 30 days after last dose of treatment (estimated to be 21 months)

• Toxicity as measured by number of study discontinuations due to treatment-related adverse events (Phase I only)

  -Toxicity is measured by CTCAE v 5.0

  Through 30 days after last dose of treatment (estimated to be 21 months)

• Progression-free survival (PFS) (Phase II or received MTD only)

  * 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.

  At 1 year

Secondary Outcomes (4)

• 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)

Study Arms (3)

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.

Drug: APL-101; Drug: Osimertinib

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.

Drug: APL-101; Drug: Osimertinib

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.

Drug: APL-101; Drug: Osimertinib

Interventions

APL-101 DRUG

-Provided by Apollomics

Phase I Dose Level 1: APL-101 + Standard of Care Osimertinib; Phase I Dose Level 2: APL-101 + Standard of Care Osimertinib; Phase II: APL-101 + Standard of Care Osimertinib

Osimertinib DRUG

-Given standard of care

Also known as: Tagrisso

Phase I Dose Level 1: APL-101 + Standard of Care Osimertinib; Phase I Dose Level 2: APL-101 + Standard of Care Osimertinib; Phase II: APL-101 + Standard of Care Osimertinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Apollomics Inc.: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

osimertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Anjali Rohatgi, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2021
• First Posted: February 8, 2021
• Study Start: January 18, 2022
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): December 31, 2029
• Last Updated: January 20, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)