AQUA07 in Patients With ALK-Positive Non-Small Cell Lung Cancer

Official title

A Phase I, Open-Label, Multicenter, Dose Escalation and Cohort Expansion Study of AQUA07 Monotherapy and Combination Therapy in Patients With Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer

Overview

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

• Drug AQUA07
  AQUA07 administrated orally
• Drug Lorlatinib
  Lorlatinib administerd orally

Primary outcome measures

• Adverse events [PartA,B] [Time frame: From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 48 months)]
• Dose-Limiting Toxicities (DLTs) [PartA,B] [Time frame: From cycle 0 day1 (if applicable) or cycle 1 day 1 to cycle 1 day 21 (each cycle is 21 days)]
• Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) and Recommendation Dose (RD) Determination [PartA,B] [Time frame: From cycle 0 day1 (if applicable) or cycle 1 day 1 to cycle 1 day 21 (each cycle is 21 days)]

Secondary outcome measures (12)

• Maximum plasma concentration (Cmax) of AQUA07 [PartA,B] [Time frame: 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)]
• Average plasma concentration (Cavg) of AQUA07 [PartA,B] [Time frame: 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)]
• Time of maximum concentration (Tmax) of AQUA07 [PartA,B] [Time frame: 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)]
• Elimination half-life (t1/2) of AQUA07 [PartA,B] [Time frame: 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)]
• Area under the plasma concentration-time curve (AUC) of AQUA07 [PartA,B] [Time frame: 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)]
• Maximum plasma concentration (Cmax) of Lorlatinib [PartB] Maximum plasma concentration (Cmax) of Lorlatinib [PartB] [Time frame: 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)]
• Average plasma concentration (Cavg) of Lorlatinib [PartB] [Time frame: 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)]
• Time of maximum concentration (Tmax) of Lorlatinib [PartB] [Time frame: 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)]
• Elimination half-life (t1/2) of Lorlatinib [PartB] [Time frame: 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)]
• Area under the plasma concentration-time curve (AUC) of Lorlatinib [PartB] [Time frame: 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)]
• Objective response related to preliminary clinical efficacy [PartA,B] [Time frame: From cycle 1 day 1 (each cycle is 21 days) until study completion or treatment discontinuation (up to approximately 48 months)]
• Duration of response (DoR) related to preliminary clinical efficacy [PartA,B] [Time frame: From cycle 1 day 1 (each cycle is 21 days) until study completion or treatment discontinuation (up to approximately 48 months)]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07617337 · AQA101CT

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗