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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: ALK Positive Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: AQUA07; Drug: Lorlatinib

• Study Type: Interventional
• Enrollment (Estimated): 102
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Clinical trials information; Phone Number: only use Email; Email: clinical-trials@chugai-pharm.co.jp

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PartA: Dose Escalation Part of AQUA07 monotherapy; Dose escalation to determine RP2D/MTD as AQUA07	Drug: AQUA07; AQUA07 administrated orally
Experimental: PartB: Dose Escalation Part of AQUA07 combotherapty with Lorlatinib; Dose escalation to determine RP2D/MTD of AQUA07 in combination with lorlatinib	Drug: Lorlatinib; Lorlatinib administerd orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events [PartA,B]	Incidence, nature and severity of adverse events	From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 48 months)
Dose-Limiting Toxicities (DLTs) [PartA,B]	Incidence and nature of DLTs	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]	Proportion of patients with course 1 DLT in each cohort	From cycle 0 day1 (if applicable) or cycle 1 day 1 to cycle 1 day 21 (each cycle is 21 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum plasma concentration (Cmax) of AQUA07 [PartA,B]	To determine the Cmax of AQUA07	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]	To determine the Cavg of AQUA07	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]	To determine the Tmax of AQUA07	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]	To determine the t1/2 of AQUA07	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]	To determine the AUC of AQUA07	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]	To determine the Cmax of Lorlatinib	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]	To determine the Cavg of Lorlatinib	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]	To determine the Tmax of Lorlatinib	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]	To determine the t1/2 of Lorlatinib	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]	To determine the AUC of Lorlatinib	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]	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	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]	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	From cycle 1 day 1 (each cycle is 21 days) until study completion or treatment discontinuation (up to approximately 48 months)
Disease control related to preliminary clinical efficacy [PartA,B]	Disease control, defined as confirmed complete response (CR), partial response (PR), or stable disease (SD) per RECIST v1.1 as determined by the Investigator	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) related to preliminary clinical efficacy [PartA,B]	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	From cycle 1 day 1 (each cycle is 21 days) until study completion or treatment discontinuation (up to approximately 48 months)

Collaborators and Investigators

• Sponsor: Chugai Pharmaceutical
• Investigators: Study Director: Sponsor Chugai Phamaceutical Co.Ltd, clinical-trials@chugai-pharm.co.jp

Study record dates

Study Major Dates

• Study Start (Estimated): July 31, 2026
• Primary Completion (Estimated): August 31, 2030
• Study Completion (Estimated): August 31, 2030

Study Registration Dates

• First Submitted: May 14, 2026
• First Submitted That Met QC Criteria: May 24, 2026
• First Posted (Actual): June 1, 2026

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 24, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: lorlatinib
• Other Study ID Numbers: AQA101CT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform. For further details on Chugai's Data Sharing Policy and how to request access to related clinical study documents, see here (www.chugai-pharm.co.jp/english/profile/rd/ctds_request.html).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No