A Study of QLC5508 Combinations in Patients With Advanced Solid Tumors

A Phase Ib/II, Open-label, Multi-center Study to Evaluate Safety, Tolerability, Pharmacokinetics and Efficacy of Intravenous Administration of QLC5508 in Combination With Other Anti-tumor Agents in Patients With Advanced Solid Tumors

QLC5508 is a fully humanized IgG1 antibody-drug conjugate (ADC) which specifically binds to B7-H3, a target wildly expressed on solid tumor cells. The objectives of this study are to investigate the safety, tolerability, pharmacokinetics and anti-tumor activity of QLC5508 in combination with other anti-cancer agents in patients with advanced solid tumor patients.

This is a phase Ib/II, open-label, multi-center, dose-escalation and expansion in Chinese subjects with advanced solid tumors. This study is in design allowing assessment of safety, tolerability, pharmacokinetics and anti-tumor activity of QLC5508 in combination with other anti-cancer agents.

The target population of dose escalation part is patients have progressed on or intolerant to available standard therapies, and the dose expansion part will enroll patients who have not received prior treatment for advanced/metastatic disease.

Inclusion Criteria:

• At least 18 years of age at screening;
• Histologically or cytologically confirmed advanced solid tumors:

Dose escalation part will enroll participants who have progressed on or are intolerant to available standard therapies.

Dose expansion part will enroll participants who have not received prior treatment for advanced/metastatic diseases.

• At least one measurable target lesion according to RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0~1
• Life expectancy ≥12 weeks
• Female or male participants should be willing to use appropriate contraceptive measures throughout the study;
• Female participants should have a negative blood pregnancy test within 7 days prior to the first dose or have evidence of non-childbearing potential;
• A signed written Informed Consent Form

Exclusion Criteria:

• . Received or undergoing any of the following treatment:

  1. Previous or current treatment with B7-H3 targeted therapy
  2. Previous or current treatment with topoisomerase I inhibitors
  3. Previous treatment with cytotoxic chemotherapy, investigational agents, traditional Chinese medicine with an anti-tumor indication and antitumor drugs within 14 days prior to the first dose
  4. Previous treatment with macromolecular antitumor drugs within 28 days prior to the first dose

  f. Radiotherapy with a limited field of radiation within 2 weeks prior to the first dose; or more than 30% of the bone marrow irradiation, or large-scale radiotherapy within 4 weeks prior to the first dose e. Pleural effusion or ascites requiring clinical intervention; or presence of pericardial effusion f. Major surgery within 4 weeks prior to the first dose g. Brain metastases; leptomeningeal or brainstem metastases; or spinal cord compression

• Unresolved AEs ≥ Grade 2 (CTCAE v5.0) from prior therapy except for alopecia and residual neuropathy

• Previous or concurrent primary malignancies

• Inadequate bone marrow reserve or organ dysfunction

• Evidence of cardiovascular risk

• Evidence of current severe or uncontrolled systemic diseases

• Severe infection within 4 weeks prior to the first dose; or uncontrolled active infection at screening

• Known or suspected interstitial lung disease; or other moderate to severe pulmonary diseases that significantly impair respiratory function and may interfere with the detection or management of drug-related pulmonary toxicity

• High risk of gastrointestinal or abdominal bleeding 10. Gastrointestinal diseases of clinical significance within 3 months prior to the first dose

• History of severe neuropathy or mental disorders

• History of severe hypersensitivity reaction, severe infusion reaction or idiosyncrasy to drugs chemically related to QLC5508 or any of the components of QLC5508

• Unlikely to comply with study procedures and requirements in the opinion of the investigator

• Any disease or condition that, in the opinion of the investigator, would compromise participant safety or interfere with study assessments