Metastatic Non Small Cell Lung CancerPhase 1/2NCT04743505
Safety and Efficacy of Combining APL-101 With Frontline Osimertinib in Patients With EGFR-mutated Metastatic Non-small Cell Lung Cancer (NSCLC)
A Phase 1/2 study testing APL-101 and Osimertinib in people with Metastatic Non Small Cell Lung Cancer, run by Washington University School of Medicine at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Non Small Cell Lung Cancer
- What is being tested?
- APL-101 and Osimertinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Jan 2022to 31 Dec 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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).
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: 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)
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
- Being tested
- APL-101, Osimertinib
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APL-101Drug
-Provided by Apollomics
OsimertinibDrug
Also called Tagrisso
-Given standard of care
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: APL-101; Drug: Osimertinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity as measured by number of study treatment related adverse events (Phase I only)
-Toxicity is measured by CTCAE v 5.0
Measured: 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
Measured: 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.
Measured: At 1 year
Secondary outcomes (4)
Maximum tolerated dose of APL-101 (MTD) (Phase I only)
- The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity during the first cycle.
Measured: 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)
- Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalization of tumor marker level.
- Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Measured: Through completion of treatment (estimated to be 20 months)
Duration of response (DOR) (Phase II or received MTD only)
-Measured from the time measurement criteria are met for complete response, partial response or stable disease (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).
Measured: Through completion of treatment (estimated to be 20 months)
Overall survival (OS) (Phase II or received MTD only)
-Overall survival (OS), defined as the duration of time from the start date of study treatment to death from any cause. Patients who are alive by the data cutoff date will be censored at the last follow up date.
Measured: Through 3 year follow-up (estimated to be 4 years and 8 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2021
- Study start18 Jan 2022
- Primary completion31 Jan 2027 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Non Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Apollomics Inc.
- Responsible party
- Sponsor
- Investigators
- Anjali Rohatgi, M.D., Ph.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04743505
- Sponsor's protocol ID
- 202104039
- Status last verified
- Jan 2026
- First submitted
- 3 Feb 2021
- Last updated
- 20 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT04743505
- Acronym / sponsor ID
- 202104039
- Conditions
- Metastatic Non Small Cell Lung Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- Apollomics Inc.
- Study start
- 18 Jan 2022 (actual)
- Primary completion
- 31 Jan 2027 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 8 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Phase I Dose Level 1: APL-101 + Standard of Care Osimertinib | Experimental | Drug: APL-101, Drug: Osimertinib* 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. |
| Phase I Dose Level 2: APL-101 + Standard of Care Osimertinib | Experimental | Drug: APL-101, Drug: Osimertinib* 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. |
| Phase II: APL-101 + Standard of Care Osimertinib | Experimental | Drug: APL-101, Drug: Osimertinib* 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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
Key exclusion criteria (17 listed)
- 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:
- Currently receiving any other investigational agents or herbal medications
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| APL-101-Provided by Apollomics | Drug | 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 |
| OsimertinibAlso: Tagrisso-Given standard of care | Drug | 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 |
Primary outcome
Toxicity as measured by number of study treatment related adverse events (Phase I only)
Time frame: 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)
Time frame: 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)
Time frame: 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.
4 secondary outcomes
Maximum tolerated dose of APL-101 (MTD) (Phase I only)
Time frame: 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)
Time frame: Through completion of treatment (estimated to be 20 months)
Duration of response (DOR) (Phase II or received MTD only)
Time frame: Through completion of treatment (estimated to be 20 months)
Overall survival (OS) (Phase II or received MTD only)
Time frame: Through 3 year follow-up (estimated to be 4 years and 8 months)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2026.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anjali Rohatgi, M.D., Ph.D. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing APL-101 and Osimertinib in people with Metastatic Non Small Cell Lung Cancer, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 20 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Toxicity as measured by number of study treatment related adverse events (Phase I only) (time frame: Through 30 days after last dose of treatment (estimated to be 21 months)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2026.