ROS1 Rearrangement Non-small Cell Lung CancerPhase 1NCT05055232

A Phase I Study of XZP-3621 in Chinese Patients With ALK or ROS1 Rearrangement Non-small Cell Lung Cancer

A Phase 1 study testing XZP-3621 in people with ROS1 Rearrangement Non-small Cell Lung Cancer and ALK Rearrangement Non-small Cell Lung Cancer, run by Xuanzhu Biopharmaceutical Co., Ltd. at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This is a multicenter, open-label, dose escalation, and expansion human clinical study to observe the safety, tolerability, pharmacokinetics, and pharmacodynamics of XZP-3621 in single and multiple oral administrations in advanced NSCLC subjects with ALK rearrangement or ROS1 rearrangement, and to initially explore… Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: ROS1 Rearrangement Non-small Cell Lung Cancer, ALK Rearrangement Non-small Cell Lung Cancer
What is being tested?: XZP-3621
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 114 participants
Where: 1 siteChina
Study dates: 12 Mar 2019to 15 Aug 2023
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male or female subjects aged 18-75 years (including 18 and 75 years);
Stage IV NSCLC or Stage IIIB and IIIC NSCLC that cannot be treated with radical radiotherapy(IASLC); Dose escalation: ALK rearrangement or ROS1 rearrangement positive, the test specimen and method is not limited;Patients were required to have experienced treatment failure or disease progression after prior ALK inhibitor therapy or were unable to afford ALK inhibitors, regardless of other previous anti-tumor therapies.
Dose expansion: ALK rearrangement or ROS1 rearrangement was confirmed by nationally approved Ventana immunohistochemistry or FISH or RT-PCR. There is no restriction on the number and type of antitumor therapy previously received; There is no limit to test time, test unit/kit and test specimen; Prior treatment was not limited, regardless of prior treatment with or without other antitumor therapy.
Dose escalation: ECOG score 0-1; Dose expansion: ECOG score 0-2;
Dose expansion: Subjects must have at least one measurable target lesion as defined by RECIST V1.1 and the lesion has not previously been treated with radiation or has had significant disease progression after radiation therapy;
All acute toxicities from prior anti-cancer treatment or complications/sequelae from surgical procedures are resolved to baseline or ≤ grade 1 (CTCAE V5.0, hair loss or other toxicities deemed by the investigator to pose no safety risk to the subject);

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All previous antitumor therapies (including chemotherapy, radiotherapy and immunotherapy) have been stopped for at least 4 weeks before the first administration of XZP-3621 (in which nitrosoreas or mitomycin should be stopped for≥ 6 weeks, and oral small molecule targeted therapy drugs and Chinese medicine (including decoction or Chinese patent medicine) should be stopped for at least 2 weeks);Palliative radiation therapy (irradiation of non-target lesions, local administration of non-target lesions) for the purpose of relieving local symptoms was allowed to be completed one week before study enrollment;
The expected survival was determined by the investigator to be 12 weeks or more;
At the time of enrollment, the subject's organ function at baseline was good, and the laboratory data met the following criteria:
Blood routine: Absolute Neutrophils Count≥1.5*109/L、PLT≥90*109/L、HGB≥90g/L;
Liver function: Serum total bilirubin ≤1.5 * ULN；ALT and AST≤3 * ULN；ALT and AST ≤5*ULN (Liver metastases subjects);
Renal function: CrCl≥50 mL/min /1.73 m2（≥0.835mL/s, according to Cockcroft-Gault formula;
AMS≤ULN (If AMS is elevated, between 1 and 2 times of ULN, but there are no other signs and clinical evidence of pancreatic disease, the subject can be included);
HbA1c≤ 7.0%;
The fertile male or female subject must agree to use an effective contraceptive method, such as a double-screen contraceptive method, a condom, oral or injectable contraceptive, an intrauterine device, etc. during the study period and within 90 days of the last dose of XZP-3621.
The subject has fully understood the study and signed the informed consent voluntarily.

Who cannot join

Subjects with primary CNS tumors or symptoms of brain metastases (except those with treated or untreated asymptomatic CNS metastases who had not been treated with corticosteroids for 2 weeks prior to enrollment, stereotactic radiotherapy for 1 week, and whole brain radiotherapy for 2 weeks prior to enrollment);
subject with small cell lung cancer;
Malignant thoracic cavity/peritoneal cavity effusion and/or pericardial effusion that cannot be controlled in the dose extension study;
Prior diagnosis of any other malignancy within 3 years prior to enrollment except for adequately treated and stable basal cell carcinoma or squamous skin cell carcinoma or carcinoma in situ of the cervix;
Subject has history of hematopoietic stem cell or bone marrow transplantation;
Subject has history of pancreatitis;

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A history of cerebrovascular accident, including transient ischemic attack or stroke, within 6 months prior to enrollment;
Major surgery (defined as surgery under general anesthesia or surgery with significant incisions) or unresolved postoperative complications prior to administration of XZP-3621 within 4 weeks prior to enrollment;
Chronic Hepatitis B(HBV), or/and HBV DNA>500 IU/ml, Hepatitis C(HCV);
known human immunodeficiency virus (HIV);
Body temperature is above 37.5℃ or significant active infections that can influence the clinical study, including active tuberculosis;
Uncontrollable electrolyte disturbances, such as low calcium, low magnesium, and low kalemia, may affect the elongation of QTc;
Unable to swallow;
History of large area diffusion/double pulmonary fibrosis, or known grade 3 or 4 pulmonary fibrosis, or current with clinically significant active pulmonary diseases, including pneumonia, allergic pneumonia, interstitial pneumonia and other interstitial lung diseases, and bronchiolitis oblationus, currently suffering from radiation pneumonia requiring hormone therapy, but not includ a history of previous radiation pneumonia;
Subjects with impaired heart function or clinically significant heart disease;
Clinically significant gastrointestinal abnormalities, including active ulcerative colitis, chronic diarrhea due to intestinal malabsorption, Crohn's disease, and/or prior surgery affecting absorption;
Any serious and/or uncontrolled comordities that the investigator believes may interfere with the study assessment, such as uncontrolled hypertension (defined as systolic blood pressure ≥140mmHg and/or diastolic blood pressure ≥90mmHg at rest) and clinically significant neurological disorders;
Subjects are receiving drugs known to strongly inhibit or induce CYP3A4 and should not stop taking them one week before administration XZP-3621 and during the study period (or within the five half-lives of the drug, whichever is longer);
The subject is scheduled for surgery, or the investigator determines that the subject needs surgery;
Participation in any other clinical trial within 1 month prior to enrollment (except those who had been removed from other clinical studies and only had survival follow-up);
Allergic constitution or a history of severe allergies;
Pregnant women and breastfeeding women;
Other conditions that the investigator considered unsuitable for inclusion.

Trial locations and contacts

1 site in 1 country.

China1 site

Shanghai Chest hospital affiliated to Shanghai jiao tong university
Shanghai, Shanghai Municipality

Other trials in China

About this study

Official title: An Open-label, Multicenter, Phase I Dose Escalation and Expansion Study of XZP-3621 in Chinese Patients With ALK or ROS1 Rearrangement Non-small Cell Lung Cancer

Read the detailed description

Dose escalation part:

The purpose of this section was to determine MTD and RP2D doses in advanced NSCLC subjects with ALK rearrangement or ROS1 rearrangement detected in tumor tissue samples or blood samples (test method is not limited).The safety and PK of single dose in human subjects in each group were first studied. After PK blood sample was collected 72 hours after single dose on day 1, continuous dose was administered once a day for 4 weeks to confirm the safety and pharmacokinetic characteristics of single dose and continuous dose.

In this study, Modified Fibonacci method was used for dose escalation. One subject was enrolled at the initial dose of 50mg. After that, according to the "3+3" dose escalation principle, the dose of 100mg (100%), 200mg (100%), 300mg (50%), 400mg (33%), 500mg (25%), 600mg (20%)and so on was incremented successively. Starting from the 100mg Qd dose group, 3 NSCLC subjects with ALK rearrangement or ROS1 rearrangement should be included per dose.If less than 3 NSCLC subjects were ALK rearrangement in any dose group due to inclusion of ROS1, and no ≥1 PR was observed in this group, additional ALK rearrangement NSCLC subjects should be added until the requirements are met. However, as long as the number of subjects in the corresponding dose group who have completed DLT observations meets the "3+3" principle of escalation, the addition of subjects to the ALK rearrangement should not affect the normal escalation of the next dose group.

Dose expansion part:

In the dose escalation study, if 2 out of 3 ALK rearrangement NSCLC subjects have a partial response (PR) or complete response (CR) after all subjects in the dose escalation study have completed DLT evaluation and confirmed that the dose is safe, that is, a dose extension study is performed from this dose to the MTD dose group. Each dose was reenrolled in about 15 NSCLC subjects with ALK rearrangement or ROS1 rearrangement demonstrated by Ventana immunohistochemistry or FISH or RT-PCR.

Subjects were treated with XZP-3621 for a 28-day treatment cycle, with continuous administration of or XZP-3621 until disease progression occurs, or an intolerable toxic reaction impeding further treatment occurs, or the investigator determines that the subject's current condition is unsuitable for further treatment, the informed consent is withdrawn, or the subject dies. RECIST efficacy was evaluated once every two treatment cycles.

During treatment, dose adjustments (both up and down) can be made according to protocol based on subjects' tolerance and the occurrence of adverse events related to the study drug. Only one dose reduction of the study drug is permitted.

Conditions: ROS1 Rearrangement Non-small Cell Lung Cancer, ALK Rearrangement Non-small Cell Lung Cancer
Being tested: XZP-3621
Keywords: XZP-3621, Dose escalation and expansion

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

XZP-3621Drug
tablets, dosage ranged from 50 mg to 600 mg, quaque die（QD）with the meal.

Study groups in NCT05055232
Study group	Role	What they receive
XZP-3621	Experimental	The first part is a dose-escalation design in patients with ALK/ROS1-positive solid tumor. The second part is an expansion in non-small cell lung Cancer (NSCLC) characterized by abnormalities in ALK expression. Receives: Drug: XZP-3621

What is being measured

The primary outcome is the main question the study is designed to answer.

Frequency of adverse events/serious adverse events
Characterization of the safety and tolerability of XZP-3621 as determined by changes in laboratory values and electrocardiograms
Measured: From screening stage to 30 days after study completion.
Incidence rate of dose limiting toxicities (DLTs) during the first cycle of treatment
Maximum Tolerated Dose(s) (MTD(s)) and/or recommended phase 2 dose (RP2D(s)) of XZP-3621 in ALK-positive non-small cell lung cancer (NSCLC) patients. Cycle = 4 weeks.
Measured: 4 weeks
Maximum tolerated dose（MTD）
The MTD is determined by the number of the participants in cohort who suffer a dose-limiting toxicity (DLT). The MTD is defined as the former dose at which more than one third of the participants develop a DLT. If no DLTs are observed, the MTD is not reached.
Measured: 4 weeks

Secondary outcomes (5)

Objective response rate(ORR)
Imaging assessments were performed every 2 treatment cycles until tumor progression/recurrence. It was defined as the proportion of patients evaluated as having complete response (CR) or partial response (PR) according to RECIST1.1 criteria
Measured: 8 weeks
Duration of response(DoR)
For subjects with CR or PR only, defined as the time from the date of first remission to the date of disease progression (PD) or death.
Measured: 8 weeks
Progress free survival(PFS)
It was defined as the time from the first study drug treatment to disease progression or death.
Measured: 8 weeks
Cmax
Pharmacokinetics of XZP-3621 by assessment of maximum plasma XZP-3621 concentration.
Measured: 4 weeks
Tmax
Pharmacokinetics of XZP-3621 by assessment of time to Cmax.
Measured: 4 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

12 Mar 201915 Aug 2023

First posted24 Sep 2021
Study start12 Mar 2019
Primary completion15 Aug 2023
Study completion15 Aug 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for ROS1 Rearrangement Non-small Cell Lung CancerStudies of the same condition, open and under way.
More trials run by Xuanzhu Biopharmaceutical Co., Ltd.The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 114 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05055232
Sponsor's protocol ID: XZP-3621-1001
Status last verified: Sep 2021
First submitted: 14 Sep 2021
Last updated: 24 Jul 2025
Results posted: No
FDA-regulated drug: No
FDA-regulated device: No

Publications

Ai X, Guo R, Zhang L, Fang J, Zhang Y, Chen J, Zhao J, Ye F, Wang S, Shi M, Zhang X, Zhang F, Li J, Wang L, Guo X, Xu L, Duan X, Hu Y, Lu S. Preclinical characterization and first-in-human, phase I trial of the novel ALK inhibitor dirozalkib in advanced non-small cell lung cancer. Eur J Cancer. 2026 Feb 25;235:116221. doi: 10.1016/j.ejca.2026.116221. Epub 2026 Jan 7.
PubMed 41539180

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1
Clinical Trial of CD40L-Augmented TIL for Patients With EGFR, ALK, ROS1 or HER2-Driven NSCLC
Non Small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer
RecruitingPhase 2
Repotrectinib in ROS1-positive Non-small Cell Lung Cancer Patients With Active Brain Metastasis
NSCLC, Brain Metastases
Active, not recruitingPhase 1
Ceritinib and Everolimus in Treating Patients With Locally Advanced or Metastatic Solid Tumors or Stage IIIB-IV Non-small Cell Lung Cancer
ALK Positive, Locally Advanced Malignant Solid Neoplasm
Active, not recruitingPhase 2
Phase 2 Platform Study in Patients With Advanced Non-Small Lung Cancer Who Progressed on First-Line Osimertinib Therapy (ORCHARD)
Non-Small Cell Lung Cancer
Not yet recruitingObservational study
Real-world Observational Study of Targeted Therapy in Patients With Advanced ROS1-positive NSCLC
Non-Small Cell Lung Cancer, ROS1 Gene Rearrangement

All ROS1 Rearrangement Non-small Cell Lung Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-label, Multicenter, Phase I Dose Escalation and Expansion Study of XZP-3621 in Chinese Patients With ALK or ROS1 Rearrangement Non-small Cell Lung Cancer
ClinicalTrials.gov ID: NCT05055232
Acronym / sponsor ID: XZP-3621-1001
Conditions: ROS1 Rearrangement Non-small Cell Lung Cancer, ALK Rearrangement Non-small Cell Lung Cancer
Keywords: XZP-3621, Dose escalation and expansion
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 114 participants (actual)
Lead sponsor: Xuanzhu Biopharmaceutical Co., Ltd.Industry (pharma, biotech, devices)
Study start: 12 Mar 2019 (actual)
Primary completion: 15 Aug 2023 (actual)
Study completion: 15 Aug 2023 (actual)
First posted: 24 Sep 2021 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Dose escalation part:

Dose expansion part:

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
XZP-3621	Experimental	Drug: XZP-3621The first part is a dose-escalation design in patients with ALK/ROS1-positive solid tumor. The second part is an expansion in non-small cell lung Cancer (NSCLC) characterized by abnormalities in ALK expression.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (16 listed)

Male or female subjects aged 18-75 years (including 18 and 75 years);
Stage IV NSCLC or Stage IIIB and IIIC NSCLC that cannot be treated with radical radiotherapy(IASLC); Dose escalation: ALK rearrangement or ROS1 rearrangement positive, the test specimen and method is not limited;Patients were required to have experienced treatment failure or disease progression after prior ALK inhibitor therapy or were unable to afford ALK inhibitors, regardless of other previous anti-tumor therapies.
Dose expansion: ALK rearrangement or ROS1 rearrangement was confirmed by nationally approved Ventana immunohistochemistry or FISH or RT-PCR. There is no restriction on the number and type of antitumor therapy previously received; There is no limit to test time, test unit/kit and test specimen; Prior treatment was not limited, regardless of prior treatment with or without other antitumor therapy.
Dose escalation: ECOG score 0-1; Dose expansion: ECOG score 0-2;
Dose expansion: Subjects must have at least one measurable target lesion as defined by RECIST V1.1 and the lesion has not previously been treated with radiation or has had significant disease progression after radiation therapy;

Key exclusion criteria (23 listed)

Subjects with primary CNS tumors or symptoms of brain metastases (except those with treated or untreated asymptomatic CNS metastases who had not been treated with corticosteroids for 2 weeks prior to enrollment, stereotactic radiotherapy for 1 week, and whole brain radiotherapy for 2 weeks prior to enrollment);
subject with small cell lung cancer;
Malignant thoracic cavity/peritoneal cavity effusion and/or pericardial effusion that cannot be controlled in the dose extension study;
Prior diagnosis of any other malignancy within 3 years prior to enrollment except for adequately treated and stable basal cell carcinoma or squamous skin cell carcinoma or carcinoma in situ of the cervix;
Subject has history of hematopoietic stem cell or bone marrow transplantation;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
XZP-3621tablets, dosage ranged from 50 mg to 600 mg, quaque die（QD）with the meal.	Drug	XZP-3621

Primary outcome

Frequency of adverse events/serious adverse events
Time frame: From screening stage to 30 days after study completion.
Characterization of the safety and tolerability of XZP-3621 as determined by changes in laboratory values and electrocardiograms
Incidence rate of dose limiting toxicities (DLTs) during the first cycle of treatment
Time frame: 4 weeks
Maximum Tolerated Dose(s) (MTD(s)) and/or recommended phase 2 dose (RP2D(s)) of XZP-3621 in ALK-positive non-small cell lung cancer (NSCLC) patients. Cycle = 4 weeks.
Maximum tolerated dose（MTD）
Time frame: 4 weeks
The MTD is determined by the number of the participants in cohort who suffer a dose-limiting toxicity (DLT). The MTD is defined as the former dose at which more than one third of the participants develop a DLT. If no DLTs are observed, the MTD is not reached.

5 secondary outcomes

Objective response rate(ORR)
Time frame: 8 weeks
Duration of response(DoR)
Time frame: 8 weeks
Progress free survival(PFS)
Time frame: 8 weeks
Cmax
Time frame: 4 weeks
Tmax
Time frame: 4 weeks

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2025.
Derived from this study: PubMed 41539180Ai X, Guo R, Zhang L, Fang J, Zhang Y, Chen J, Zhao J, Ye F, Wang S, Shi M, Zhang X, Zhang F, Li J, Wang L, Guo X, Xu L, Duan X, Hu Y, Lu S. Preclinical characterization and first-in-human, phase I trial of the novel ALK inhibitor dirozalkib in advanced non-small cell lung cancer. Eur J Cancer. 2026 Feb 25;235:116221. doi: 10.1016/j.ejca.2026.116221. Epub 2026 Jan 7.

Related trials for ROS1 Rearrangement Non-small Cell Lung Cancer

RecruitingPhase 1
Clinical Trial of CD40L-Augmented TIL for Patients With EGFR, ALK, ROS1 or HER2-Driven NSCLC
Non Small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer
RecruitingPhase 2
Repotrectinib in ROS1-positive Non-small Cell Lung Cancer Patients With Active Brain Metastasis
NSCLC, Brain Metastases
Active, not recruitingPhase 1
Ceritinib and Everolimus in Treating Patients With Locally Advanced or Metastatic Solid Tumors or Stage IIIB-IV Non-small Cell Lung Cancer
ALK Positive, Locally Advanced Malignant Solid Neoplasm
Active, not recruitingPhase 2
Phase 2 Platform Study in Patients With Advanced Non-Small Lung Cancer Who Progressed on First-Line Osimertinib Therapy (ORCHARD)
Non-Small Cell Lung Cancer
Not yet recruitingObservational study
Real-world Observational Study of Targeted Therapy in Patients With Advanced ROS1-positive NSCLC
Non-Small Cell Lung Cancer, ROS1 Gene Rearrangement

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Shun Lu, MD principal investigator

Shanghai Chest hospital affiliated to Shanghai jiao tong university

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Frequency of adverse events/serious adverse events (time frame: From screening stage to 30 days after study completion.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05055232, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2025.