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

NCT05055232 | Completed Phase 1

• 1 other identifier: XZP-3621-1001
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 1

Brief 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 the efficacy of XZP-3621.The study was divided into two parts: dose escalation and dose expansion.

Conditions

ROS1 Rearrangement Non-small Cell Lung Cancer; ALK Rearrangement Non-small Cell Lung Cancer

Keywords

XZP-3621; Dose escalation and expansion

Outcome Measures

Primary Outcomes (3)

• 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

  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.

  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.

  4 weeks

Secondary Outcomes (5)

• Objective response rate(ORR)

  8 weeks

• Duration of response(DoR)

  8 weeks

• Progress free survival(PFS)

  8 weeks

• Cmax

  4 weeks

• Tmax

  4 weeks

Study Arms (1)

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.

Drug: XZP-3621

Interventions

XZP-3621 DRUG

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

XZP-3621

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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);
• 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.

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• Xuanzhu Biopharmaceutical Co., Ltd.: lead

Study Sites (1)

Shanghai Chest hospital affiliated to Shanghai jiao tong university

Shanghai, Shanghai Municipality, China

Location

Related Publications (1)

• 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 Jan 7;235:116221. doi: 10.1016/j.ejca.2026.116221. Online ahead of print.

  PMID: 41539180 DERIVED

Study Officials

• Shun Lu, MD

  Shanghai Chest hospital affiliated to Shanghai jiao tong university

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2021
• First Posted: September 24, 2021
• Study Start: March 12, 2019
• Primary Completion: August 15, 2023
• Study Completion: August 15, 2023
• Last Updated: July 24, 2025

Record last verified: 2021-09

Locations

CN (1)