Phase 1/2, Open-Label, Multi-Center Trial to Assess Safety, Tolerability, Pharmacokinetics , Pharmacodynamics, and Efficacy of CLN-081 in Patients with Locally-Advanced or Metastatic Non-Small Cell Lung Cancer Harboring EGFR Exon 20 Insertion Mutations Who Have Previously Received Platinum-Based Systemic Chemotherapy

Recruiting

Conditions: lung cancer
NSCLC
10029107

Registration Number: NL-OMON56206

Lead Sponsor: Cullinan Oncology Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 32

Inclusion Criteria

A patient who meets all of the following inclusion criteria will be eligible to
participate in this study:
1. Histologically or cytologically confirmed recurrent and/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 insertionex20ins mutation demonstrated by a
validated test routinely used by each institutionlisted in Section 9.7 and
performed in a Clinical Laboratory Improvement Amendments (CLIA-)-certified or
equivalent laboratory (all patients other than Module A Food Effect PK
Assessment Module). Institutions that don*t have access to these tests should
contact the sponsor for assistance.
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 × ULNupper 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. Aspartate transaminase and alanine transaminaseAST 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 × 109 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 ×109 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 and comply with study procedures.

Exclusion Criteria

R6, Phase 1 Expansion, Phase 2a, Module A and Module B Patients Only
1. Prior treatment with an EGFR ex20ins -targeting drug (eg, including, but not
limited to poziotinib, mobocertinib, amivantamab, DZD9008, BDTX-189).
Note: enrolment of patients treated previously with EGFR ex20ins targeting
drugs allowed selectively during accelerated titration dose escalation and
Module C only.
Module A Food Effect PK Assessment Module patients only
2. Conditions that compromise esophageal or GI function, including esophageal,
gastric, hepatobiliary, or small bowel carcinomas or history of gastric
resection.
3. Recurrent diarrhea, nausea, or vomiting.
4. Unable to refrain from or anticipates the use of:
a. Any drug, including prescription and non-prescription medications, including
drugs that change gastrointestinal motility (eg, loperamide) or gastric pH (eg,
antacids, H2 antagonists, proton pump inhibitors), herbal remedies, or vitamin
supplements within 14 days prior to the first dosing on Day 1 to follow-up.
b. Any drugs known to be inhibitors or inducers of cytochrome P450 (CYP)3A
enzymes and/or p-glycoprotein (P-gp), including St. John*s Wort and grapefruit
juice, within 28 days prior to the first dosing and throughout the PK
assessment.
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, have
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 × the terminal phase elimination half-lives,
whichever is longer, prior to the first dose of study drug on C1D1
b. Systemic anticancer treatment (excluding EGFR TKIs as described above) <= 14
days prior to the first dose of study drug on C1D1.
c. 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.
d. Immunotherapy <= 28 days prior to the first dose of study drug on C1D1.
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 enroll 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, treatment-related
pneumonitis, or any evidence of clinically active interstitial lung disease.
15. Cardiac conditions as follows: Patient has a history of congestive

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The rate and severity of treatment emergent AEs, DLTs, SAEs, incidence of<br /><br>safety laboratory assessment abnormalities<br /><br>Incidence of abnormalities in vital signs or other clinical safety assessments<br /><br>ORR based upon both independent central review and local Investigator<br /><br>assessment by RECIST v1.1<br /><br>Tumor response characteristics including DOR, DCR, PFS, and time to tumor<br /><br>response based upon both independent central review and local investigator<br /><br>assessment and OS<br /><br>CLN-081 PK<br /><br>Metabolite identification<br /><br>Other biomarker data<br /><br>Diagnostic tumor samples<br /><br>Please refer to protocol for Primary Objectives of Phase 2a, Module A, Module B<br /><br>part 1 and Module B part 2.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>To assess the anti-tumor activity of orally administered CLN-081 monotherapy.<br /><br>To characterize select pharmacokinetics (PK) parameters associated with orally<br /><br>administered CLN-081 monotherapy.<br /><br>To assess activity of orally administered CLN-081 monotherapy in patients with<br /><br>known central nervous system (CNS) disease.<br /><br>Please refer to protocol for Secondary Objectives of Phase 2a, Module A, Module<br /><br>B part 1 and Module B part 2.</p><br>