Phase 1/2 Study of CLN-081 in Patients with Lung Cancer

Phase 1

• Conditions: on-Small Cell Lung Cancer Harboring EGFR Exon 20 Insertion Mutations; MedDRA version: 21.1Level: PTClassification code 10029515Term: Non-small cell lung cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-002409-23-NL
• Lead Sponsor: Cullinan Oncology Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-10-14
• Last Update Posted: 13 November 2023

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 369

Inclusion Criteria

1. Histologically or cytologically confirmed locally advanced or
metastatic NSCLC (all patients). For module A only, histologically or
cytologically confirmed solid tumor with the exception of esophageal,
gastric, pancreatic, hepatobiliary, or small bowel carcinomas, or history of gastric resection.
2. Documented EGFR exon 20 insertion (ex20ins) mutation
demonstrated by a validated test (per protocol) and performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified or equivalent laboratory (all patients other than Module A Food Effect PK Assessment Module).
3. Prior treatment in the recurrent/metastatic disease setting including:
a. A platinum-based chemotherapy regiment (or other chemotherapy
regimen if platinum-based chemotherapy is contra-indicated)
b. 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 record.
c. No prior therapy is required for patients enrolled on Module A.
d. Prior therapy with an agent approved by the local regulatory authorities for the treatment of EGFR ex20ins mutant NSCLC (Module C only).
4. Measurable disease by Response Evaluation Criteria in Solid Tumors
(RECIST) 1.1 (except for patients enrolled on Module A).
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:
a. Serum creatinine < 1.5 × upper limit of normal (ULN) or if higher than
normal range, calculated creatinine clearance (CrCl) must be = 50 mL/min/1.73 m2 (if calculated by Cockroft-Gault formula, the actual body weight must be used for CrCl unless body mass index [BMI] >30 kg/m2 then lean body weight must be used).
b. Total bilirubin = 1.5 × ULN unless prior history of Gilbert's syndrome.
c. AST and ALT = 2.5 × ULN, or = 5 × ULN if due to liver involvement by
tumor.
d. Hemoglobin = 9.0 g/dL in the absence of transfusion = 14 days prior
to the first dose of study drug on C1D1.
e. Platelets = 100 × 10E9 cells/L in the absence of transfusion <14 days
prior to the first dose of study drug on Cycle 1 Day 1 (C1D1).
f. Absolute neutrophil count = 1.5 ×10E9 cells/L.
9. For Module A patients only: patients must have a negative coronavirus
disease 2019 (COVID-19) polymerase chain reaction test prior to
enrolment.
10. For Module B and Module C patients only: verification of suitable
archived tumor tissue available at the participating center for biomarker analysis. A fresh biopsy is required if an archived sample is not available.
11. Ability to understand and the willingness to sign a written informed
consent document.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 185
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 184

Exclusion Criteria

R6, Phase 1 Expansion, Phase 2a, Module A and Module B Patients Only
1. Prior treatment with an EGFR ex20ins-targeting drug (see protocol for
examples). Note: enrolment of patients treated previously with EGFR ex20ins-targeting drugs allowed selectively during accelerated titration dose escalation and Module C only.
Module A Patients Only
2. Conditions that compromise esophageal or gastrointestinal (GI)
function.
3. Recurrent diarrhea, nausea, or vomiting.
4. Unable to refrain from or anticipates use of any drug, including
prescription and non-prescription medications (see protocol) for the periods defined in the protocol.
5. Any allergies to the composition of the high fat meal.
6. Patients who use tobacco products.
All Patients
7. History of COVID-19-related pneumonitis requiring hospitalization.
8. History of COVID-19 infection within 4 weeks prior to enrolment, or
clinically significant pulmonary symptoms related to prior COVID-19
pneumonitis.
9. Treatment with any of the following:
a. An EGFR TKIs = 8 days or 5 x the terminal phase elimination halflives,
whichever is longer, prior to first dose of study drug on C1D1
b. Systemic anticancer treatment (excluding EGFR-TKIs as described
above) within 14 days prior to the first dose of study drug on C1D1.
c. Immunotherapy = 28 days prior to the first dose of study drug on
C1D1.
d. 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 being eligible for evaluation as target lesions.
e. Major surgery (excluding placement of vascular access) = 28 days of the first dose of study drug on C1D1.
10. 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 enrol after
agreement between the Investigator and Sponsor.
11. Have known or suspected leptomeningeal metastasis. Have known or suspected brain metastases or spinal cord compression, unless the
condition has been asymptomatic, treated with surgery and/or radiation (if clinically indicated), 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.
12. Prior therapy with CLN-081.
13. Known hypersensitivity to CLN-081 or any drugs similar in structure or class.
14. Past medical history of interstitial lung disease, drug-induced interstitial lung disease, treatment-related pneumonitis, or any evidence of clinically active interstitial lung disease.
15. Cardiac conditions as follows: Patient has a history of CHF Class
III/IV according to the NYHA Functional Classification or serious cardiac arrhythmias requiring treatment.
16. Resting QTcF > 470 msec.
17. Patient is unable to take drugs orally due to disorders or diseases
that may affect GI function,including but not limited to inflammatory
bowel diseases or
malabsorption syndrome, or procedures that may affect gastrointestinal
function, such as gastrectomy, enterectomy, or colectomy.
18. 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.
19. Pregnant or lactating females; FOCBP must have a negative serum
pregnancy test at within seven days prior to receiving study drug on

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified