A Study of DXC006 With Immune Checkpoint Inhibitors or Platinum for Small Cell Lung Cancer.

Official title

A Phase Ib/II Study to Evaluate the Safety and Efficacy of DXC006 for Injection Combined With Immune Checkpoint Inhibitors or Platinum-Based Agents in Patients With Small Cell Lung Cancer.

Overview

This is a Phase Ib/II, open-label clinical study designed to evaluate the safety, tolerability, preliminary anti-tumor activity, recommended Phase 2 dose (RP2D), pharmacokinetic (PK) characteristics, and immunogenicity of DXC006 in combination with an immune checkpoint inhibitor (ICI) or platinum-based chemotherapy in patients with small cell lung cancer (SCLC).

Interventions

• Drug DXC006
  Participants receive DXC006 intravenously on Day 1 every 3 weeks.
• Drug Toripalimab
  Participants receive Toripalimab intravenously on Day 1 every 3 weeks.
• Drug Carboplatin
  Participants receive Carboplatin intravenously on Day 1 every 3 weeks (up to 6 cycles).
• Drug Cisplatin
  Participants receive Cisplatin intravenously on Day 1 every 3 weeks (up to 6 cycles).

Primary outcome measures

• Progression Free Survival (PFS) [Time frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 year.]
• 6-month progression-free survival rate [Time frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months.]
• Recommended Phase 2 Dose (RP2D) [Time frame: Final RP2D confirmation upon completion of the Phase Ib (up to 12 months).]
• Measurement of objective response rate (ORR) per RECIST 1.1 [Time frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 year.]
• Measurement of disease control rate (DCR) [Time frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 year.]
• Incidence of Adverse Events (AEs) [Time frame: After first infusion of study drug, through study completion an average of 2 year.]

Secondary outcome measures (12)

• Maximum observed serum or plasma concentration (Cmax) [Time frame: Through study completion an average of 1 year.]
• Maximum serum drug time（Tmax） [Time frame: Through study completion an average of 1 year.]
• Apparent volume of distribution(Vd) [Time frame: Through study completion an average of 1 year.]
• Volume of distribution at steady state (Vss) [Time frame: Through study completion an average of 1 year.]
• Terminal phase elimination half life (t½) [Time frame: Through study completion an average of 1 year.]
• Area under the serum or plasma concentration time curve from 0 to the last measurable point (AUC0-t). [Time frame: Through study completion an average of 1 year.]
• Area under the serum or plasma concentration time curve from 0 to infinity (AUC0-inf) [Time frame: Through study completion an average of 1 year.]
• Clearance (CL) [Time frame: Through study completion an average of 1 year.]
• Ctrough [Time frame: Through study completion an average of 1 year.]
• Anti-drug antibodies (ADA) [Time frame: Through study completion an average of 1 year.]
• Overall Survival (OS) [Time frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 year.]
• Duration of response (DOR) [Time frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 year.]

Eligibility criteria

Inclusion criteria

• Voluntarily signed informed consent and willingness to comply with the protocol requirements.
• Male or female.
• Age ≥18 years and ≤75 years.
• Life expectancy ≥3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.
• Histologically or cytologically confirmed small cell lung cancer (SCLC).
• Toxicity from prior anti-tumor therapy has resolved to ≤ Grade 1 as defined by NCI-CTCAE version 6.0 (except alopecia); peripheral neuropathy must have completely resolved.
• Adequate hepatic, renal, coagulation, and cardiac function.
• The participant and their spouse agree to use effective barrier or pharmacologic contraception (excluding rhythm method) from the time of signing the informed consent until 6 months after the last dose of study treatment.

Exclusion criteria

• Histologically or cytologically confirmed combined SCLC, NSCLC, sarcomatoid carcinoma, or large cell neuroendocrine carcinoma.
• Within 14 days prior to the first dose: underwent plasmapheresis; received systemic corticosteroid therapy at a daily dose >10 mg prednisone or equivalent (or equivalent anti-inflammatory activity) for more than 3 consecutive days (short-term use for prevention of contrast media allergy is permitted).
• Prior allogeneic hematopoietic stem cell transplantation (HSCT) or history of solid organ transplantation.
• Prior treatment with CD56-targeted therapy.
• Symptomatic brain metastases or leptomeningeal metastases.
• History of severe or life-threatening immune-related adverse events or infusion-related reactions (including permanent discontinuation of immuno-oncology therapy due to intolerance).
• Active autoimmune disease or immunodeficiency, or a history of such conditions.
• Evidence of significant cardiovascular risk.
• Dyspnea or current requirement for continuous supplemental oxygen therapy, or current active pneumonitis or interstitial lung disease (except mild cases as determined by the investigator).
• History of other primary malignancies, with the exception of malignancies that have been cured and have a very low risk of recurrence within 5 years, such as basal cell carcinoma or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast.
• Severe non-healing wound, ulcer, or bone fracture; or major surgery within 28 days prior to dosing, or anticipated major surgery during the study period.
• History of hypersensitivity to any component or excipient of DXC006, immune checkpoint inhibitors, or platinum-based chemotherapy.
• Active hepatitis B (HBV-DNA above the upper limit of normal at the central laboratory or >1000 copies/mL); hepatitis C infection (positive hepatitis C antibody or positive HCV RNA PCR result).
• Known positive serology for human immunodeficiency virus (HIV); active syphilis (patients with positive syphilis antibody only are eligible); potential active pulmonary tuberculosis (chest imaging within 3 months prior to the first dose suggestive of active tuberculosis infection).
• Active bleeding within 30 days prior to screening, or risk of major gastrointestinal bleeding or hemoptysis as determined by the investigator; or hereditary bleeding tendency, coagulopathy, or bleeding symptoms requiring other medical intervention.
• Severe arterial or venous thromboembolic events within 6 months prior to study drug administration, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis, or pulmonary embolism.
• Positive serum pregnancy test or currently breastfeeding female participants.
• Active infection requiring medical therapy (CTCAE Grade ≥2); uncontrollable pleural effusion, ascites, or pericardial effusion requiring repeated drainage.
• Administration of live attenuated vaccines within 28 days prior to the first dose.
• Other conditions that, in the judgment of the investigator, may affect the patient's participation in the study.
• Poor general condition, such as requirement for mechanical ventilation and/or intravenous catecholamine infusion, and/or severe neurological impairment, coma, and/or quadriplegia with complete loss of communication ability (deafness, blindness, aphasia); uncontrolled seizures; other psychiatric disorders that may affect study participation.

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

China · 1 center

• Sun Yat-sen University Cancer Center — Guangzhou

Identifiers

NCT: NCT07559929 · DXC006-002

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗