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 2a 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 demonstrated by a test routinely used by
each institution and performed in a CLIA-certified or equivalent laboratory.
3. Prior treatment in the recurrent/metastatic disease setting including:
1. A platinum-based chemotherapy regimen (or other chemotherapy regimen if
platinum-based chemotherapy is contra-indicated)
2. Any other approved standard therapy that is available to the patient, unless this
therapy is contraindicated, intolerable to the patient, or is declined by the
patient. In the case of a patient declining such therapy, documentation that the
patient has been informed and declined should be documented in the medical
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
and comply with study procedures.
1. Prior Exon 20 Patients Only
a. No Prior treatment with an EGFR exon 20 insertion-targeting drug (e.g., poziotinib,
TAK788, tarloxotinib, JNJ-61186372).
2. Rolling Six, Phase 1 Expansion, and Phase 2a Expansion Patients Only
a. Prior treatment with an EGFR exon 20 insertion-targeting drug (e.g., poziotinib,
TAK788, tarloxotinib, JNJ-61186372).
3. All Patients
Treatment with any of the following:
1. An EGFR tyrosine kinase inhibitors (TKIs) ≤ 8 days or 5x the terminal phase
elimination half-lives, whichever is longer, prior to the first dose of study
drug on C1D1
2. Systemic anticancer treatment (excluding EGFR-TKIs as described above) ≤ 14 days
prior to the first dose of study drug on C1D1.
3. Radiotherapy < 28 days and palliative radiation ≤ 14 days prior to the first dose
of study drug on C1D1. If irradiated, lesions must have demonstrated clear-cut
progression prior to to being eligible for evaluation as target lesions.
4. Immunotherapy ≤ 28 days prior to the first dose of study drug on C1D1.
5. Major surgery (excluding placement of vascular access) ≤ 28 days 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. Patients with chronic, but stable Grade 2
toxicities may be allowed to enroll after agreement between the Investigator and
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. Past medical history of interstitial lung disease, drug-induced interstitial lung
disease, radiation pneumonitis which required steroid treatment, or any evidence of
clinically active interstitial lung disease.
10. Resting corrected QT interval (QTc) > 470 msec.
11. 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.
12. 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.
13. 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
14. 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.
15. Uncontrolled intercurrent illness including, but not limited to, uncompensated
respiratory, cardiac, hepatic, or renal disease, active infection (including 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.
16. For patients with a history of hepatitis B, active infection as defined by a positive
HBsAg test and detectable HBV DNA. Patients ineligible due to detectable levels of HBV
DNA at baseline may be rescreened for enrollment if their HBV DNA levels become
undetectable after treatment with antiviral agents, and upon agreement between the
investigator and Sponsor.
17. For patients with a history of hepatitis C, active infection as defined by a reactive
HCV antibody test and detectable HCV RNA.
18. Active bleeding disorders.
19. Is, in the Investigator's opinion, unable or unwilling to comply with the trial