CLN-081-101 is a Phase 1/2a, open label, multi-center study of CLN-081 in patients with NSCLC
(non small cell lung cancer) harboring EGFR (epidermal growth factor receptor) exon 20
insertion mutations, to determine the maximum tolerated dose (MTD) and recommended Phase 2
dose (RP2D), as well as to evaluate preliminary efficacy.
This is a Phase 1/2a, open-label, multicenter, first-in-human trial to evaluate the safety
and tolerability, PK, PD, and preliminary efficacy of CLN-081 in patients with non-small cell
lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion
This trial is divided into three parts: Phase 1 Dose Escalation, Phase 1 Dose Expansion, and
Phase 2s Dose Expansion.
The objectives of the dose escalation part are to determine the safety, tolerability, MTD,
recommended Phase 2 dose (RP2D), and to evaluate the anti-tumor activity of orally
administered CLN-081 monotherapy. Additional objectives are to determine the pharmacokinetic
(PK) profile of CLN-081 and CLN-081's activity in patients with known central nervous system
CLN-081 will be dosed once daily (QD) and twice daily (BID).
1. Histologically or cytologically confirmed recurrent, metastatic NSCLC.
2. Documented EGFR exon 20 insertion mutation may be demonstrated by:
1. An FDA-approved device including cobas EGFR Mutation Test v2, therascreen EGFR
RGQ PCR Kit, FoundationOne CDx, or MSK-IMPACT, or
2. A device or test validated and accepted by regulatory health authorities outside
the United States for patients enrolled in the trial outside of the United
3. At least one prior treatment with platinum-based chemotherapy. Note: Prior treatment
with a PD-1/PD-L1 inhibitor is allowed but not required.
4. Measurable disease by RECIST 1.1.
5. Age ≥ 18 years.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
7. Ability to take pills by mouth.
8. Have the following laboratory values:
1. Serum creatinine < 1.5 × ULN or if higher than normal range, calculated
creatinine clearance (CrCl) must be ≥ 50 mL/min/1.73 m2 (by Cockroft-Gault
formula); actual body weight must be used for CrCl unless BMI > 30 kg/m2 then
lean body weight must be used.
2. Total bilirubin ≤ 1.5 × ULN unless prior history of Gilbert's syndrome.
3. Aspartate transaminase and alanine transaminase ≤ 2.5 × ULN, or ≤ 5 × ULN if due
to liver involvement by tumor.
4. Hemoglobin ≥ 9.0 g/dL.
5. Platelets ≥ 100 × 109 cells/L.
6. Absolute neutrophil count ≥ 1.5 ×109 cells/L.
9. Ability to understand and the willingness to sign a written informed consent document.
1. Accelerated Titration Patients Only
a. Any EGFR tyrosine kinase inhibitors (TKIs), e.g., gefitinib, erlotinib, afatinib,
and osmertinib, ≤ 8 days or 5x the terminal phase elimination half-lives, whichever is
longer, prior to the first dose of study drug on C1D1.
2. Rolling Six, Phase 1 Expansion, and Phase 2a Expansion Patients Only
Prior treatment with any of the following:
1. An EGFR-TKI of > 6 months in which the patient derived clinical benefit.
2. An EGFR exon 20 insertion-targeting drug (e.g., poziotinib, TAK788) for > 2
cycles or discontinuation due to progressive disease.
Note: Patients that discontinued an EGFR 20 insertion-targeting inhibitor for other
reasons (e.g, intolerability) and have received ≤ 2 cycles of treatment may not be
excluded upon agreement between the Investigator and Sponsor.
3. All Patients
Treatment with any of the following:
1. Systemic anticancer treatment (excluding EGFR-TKIs as described above) ≤ 14 days
prior to the first dose of study drug on C1D1.
2. Limited-field radiotherapy ≤ 7 days or extended-field thoracic radiotherapy < 4
weeks of study drug on C1D1.
3. Major surgery (excluding placement of vascular access) ≤ 4 weeks of the first
dose of study drug on C1D1.
4. Have any unresolved toxicity of Grade ≥ 2 from previous anti-cancer treatment, except
for alopecia and skin pigmentation.
5. Have known or suspected brain metastases or spinal cord compression, unless the
condition has been asymptomatic, treated with surgery and/or radiation, and has been
stable without requiring escalating corticosteroids or anti-convulsant medications for
at least four weeks prior to the first dose of study drug on C1D1.
6. Prior therapy with CLN-081.
7. Known hypersensitivity to CLN-081 or any drugs similar in structure or class.
8. Cardiac conditions as follows: Patient has a history of congestive heart failure (CHF)
Class III/IV according to the New York Heart Association (NYHA) Functional
Classification or serious cardiac arrhythmias requiring treatment.
9. Mean resting corrected QT interval (QTc) > 470 msec obtained from three
10. Patient is unable to take drugs orally due to disorders or diseases that may affect
gastrointestinal function, such as inflammatory bowel diseases (e.g., Crohn's disease,
ulcerative colitis) or malabsorption syndrome, or procedures that may affect
gastrointestinal function, such as gastrectomy, enterectomy, or colectomy.
11. Have any condition or illness that, in the opinion of the investigator, might
compromise patient safety or interfere with the evaluation of the safety of the drug.
12. Pregnant or lactating women; women of child-bearing potential (WOCBP) must have a
negative serum pregnancy test ≤ 7 days prior to receiving study drug on C1D1. WOCBP
and males with partners of child-bearing potential must agree to use adequate birth
control throughout their participation and for six months following the last dose of
13. History of another primary malignancy ≤ 2 years prior to starting study drug on C1D1,
except for adequately treated basal or squamous cell carcinoma of the skin or cancer
of the cervix in situ.
14. Uncontrolled intercurrent illness including, but not limited to, uncompensated
respiratory, cardiac, hepatic, or renal disease, active infection (including hepatitis
B, hepatitis C, HIV, and active clinical tuberculosis), or renal transplant; ongoing
or active infection, symptomatic congestive heart failure, unstable angina pectoris,
cardiac arrhythmia, active peptic ulcer disease or gastritis, or psychiatric
illness/social situations that would limit compliance with study requirements.
15. Active bleeding disorders.
16. Is, in the Investigator's opinion, unable or unwilling to comply with the trial