ALK Positive Non-small Cell Lung Cancer
Conditions
Brief summary
This is a first-in-human, Phase I, open-label, multicenter, multinational study, designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and anti-tumor activity of AQUA07 when administered as single agent and in combination with lorlatinib in patients with ALK positive non-small cell lung cancer.
Interventions
DRUGAQUA07
AQUA07 administrated orally
DRUGLorlatinib
Lorlatinib administerd orally
Sponsors
Chugai Pharmaceutical
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years (or ≥ 20 years if required by local regulation) at time of signing Informed Consent Form * Previously treated with at least one ALK-TKI regardless of prior chemotherapy treatment (Patients who have received only crizotinib as prior ALK-TKI treatment will not be allowed.) * Histologically or cytologically (excluding sputum cytology) proven diagnosis of locally advanced unresectable or metastatic ALK-positive NSCLC * Measurable disease per RECIST v1.1 * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Ability and willingness to take oral medication(s) * Adequate organ function and bone marrow reserve
Exclusion criteria
* Prior toxicities from anti-cancer therapy which have not resolved to Grade ≤ 1 per NCI CTCAE v5.0 excluding alopecia, vitiligo, or endocrinopathies manageable with replacement therapy * Symptomatic, active CNS metastases or untreated CNS metastases requiring any definitive therapy. * Severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or renal disease, or active infection), or with a history or complication of interstitial lung disease * Significant cardiovascular disease * Inadequately controlled hypertension
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-Limiting Toxicities (DLTs) [PartA,B] | From cycle 0 day1 (if applicable) or cycle 1 day 1 to cycle 1 day 21 (each cycle is 21 days) | Incidence and nature of DLTs |
| Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) and Recommendation Dose (RD) Determination [PartA,B] | From cycle 0 day1 (if applicable) or cycle 1 day 1 to cycle 1 day 21 (each cycle is 21 days) | Proportion of patients with course 1 DLT in each cohort |
| Adverse events [PartA,B] | From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 48 months) | Incidence, nature and severity of adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time of maximum concentration (Tmax) of AQUA07 [PartA,B] | From cycle 0 day 1 (if applicable) or cycle 1 day 1 (each cycle is 21 days) until study completion or treatment discontinuation (up to approximately 48 months) | To determine the Tmax of AQUA07 |
| Elimination half-life (t1/2) of AQUA07 [PartA,B] | From cycle 0 day 1 (if applicable) or cycle 1 day 1 (each cycle is 21 days) until study completion or treatment discontinuation (up to approximately 48 months) | To determine the t1/2 of AQUA07 |
| Area under the plasma concentration-time curve (AUC) of AQUA07 [PartA,B] | From cycle 0 day 1 (if applicable) or cycle 1 day 1 (each cycle is 21 days) until study completion or treatment discontinuation (up to approximately 48 months) | To determine the AUC of AQUA07 |
| Maximum plasma concentration (Cmax) of Lorlatinib [PartB] Maximum plasma concentration (Cmax) of Lorlatinib [PartB] | From cycle 0 day 1 (if applicable) or cycle 1 day 1 (each cycle is 21 days) until study completion or treatment discontinuation (up to approximately 48 months) | To determine the Cmax of Lorlatinib |
| Average plasma concentration (Cavg) of Lorlatinib [PartB] | From cycle 0 day 1 (if applicable) or cycle 1 day 1 (each cycle is 21 days) until study completion or treatment discontinuation (up to approximately 48 months) | To determine the Cavg of Lorlatinib |
| Time of maximum concentration (Tmax) of Lorlatinib [PartB] | From cycle 0 day 1 (if applicable) or cycle 1 day 1 (each cycle is 21 days) until study completion or treatment discontinuation (up to approximately 48 months) | To determine the Tmax of Lorlatinib |
| Elimination half-life (t1/2) of Lorlatinib [PartB] | From cycle 0 day 1 (if applicable) or cycle 1 day 1 (each cycle is 21 days) until study completion or treatment discontinuation (up to approximately 48 months) | To determine the t1/2 of Lorlatinib |
| Area under the plasma concentration-time curve (AUC) of Lorlatinib [PartB] | From cycle 0 day 1 (if applicable) or cycle 1 day 1 (each cycle is 21 days) until study completion or treatment discontinuation (up to approximately 48 months) | To determine the AUC of Lorlatinib |
| Objective response related to preliminary clinical efficacy [PartA,B] | From cycle 1 day 1 (each cycle is 21 days) until study completion or treatment discontinuation (up to approximately 48 months) | Objective response, defined as a confirmed complete response (CR) or partial response (PR) as the best overall response according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as determined by the Investigator |
| Duration of response (DoR) related to preliminary clinical efficacy [PartA,B] | From cycle 1 day 1 (each cycle is 21 days) until study completion or treatment discontinuation (up to approximately 48 months) | DoR is defined as the time from the first occurrence of a documented objective response to the time of the first documented disease progression per RECIST v1.1 as determined by the Investigator, or death from any cause, whichever occurs first |
| Progression-Free Survival (PFS) related to preliminary clinical efficacy [PartA,B] | From cycle 1 day 1 (each cycle is 21 days) until study completion or treatment discontinuation (up to approximately 48 months) | Progression-free survival (PFS), defined as the time from the first day of study treatment to the first occurrence of disease progression per RECIST v1.1 as determined by the Investigator, or death from any cause, whichever occurs first |
| Disease control related to preliminary clinical efficacy [PartA,B] | From cycle 1 day 1 (each cycle is 21 days) until study completion or treatment discontinuation (up to approximately 48 months) | Disease control, defined as confirmed complete response (CR), partial response (PR), or stable disease (SD) per RECIST v1.1 as determined by the Investigator |
| Maximum plasma concentration (Cmax) of AQUA07 [PartA,B] | From cycle 0 day 1 (if applicable) or cycle 1 day 1 (each cycle is 21 days) until study completion or treatment discontinuation (up to approximately 48 months) | To determine the Cmax of AQUA07 |
| Average plasma concentration (Cavg) of AQUA07 [PartA,B] | From cycle 0 day 1 (if applicable) or cycle 1 day 1 (each cycle is 21 days) until study completion or treatment discontinuation (up to approximately 48 months) | To determine the Cavg of AQUA07 |
Countries
Japan
Contacts
CONTACTClinical trials information
STUDY_DIRECTORSponsor Chugai Phamaceutical Co.Ltd
clinical-trials@chugai-pharm.co.jp
Outcome results
None listed