A Phase Ib/II Clinical Trial to Evaluate the Preliminary Efficacy, Safety and Pharmacokinetics of PM8002 Injection Combined With PM1009 Injection in Patients With Locally Advanced or Metastatic Hepatocellular Carcinoma
Overview
- Phase
- Phase 1
- Intervention
- PM8002
- Conditions
- HCC
- Sponsor
- Biotheus Inc.
- Enrollment
- 140
- Primary Endpoint
- Objective response rate(ORR)
- Status
- Not yet recruiting
- Last Updated
- last year
Overview
Brief Summary
This study to evaluate the preliminary efficacy, safety and pharmacokinetics of PM8002 combined with PM1009 in Patients with first-line Hepatocellular Carcinoma.
Detailed Description
The study is divided into two parts. The first part is a phase Ib, single-arm study, which is planned to enroll 3-28 subjects. The second part is a phase II randomized, parallel-controlled, four-arm, open-label study, which is planned to enroll approximately 120 subjects.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Voluntary participation in clinical studies;
- •Male or female, aged ≥ 18 years;
- •Pathologically or clinically confirmed (according to AASLD), unresectable locally advanced and/or metastatic HCC;
- •Child-Pugh liver function score ≤7；
- •No prior systemic therapy for locally advanced or metastatic and/or unresectable HCC；
- •At least 1 measurable lesion ；
- •Adequate organ function；
- •ECOG score of 0 to 1；
- •Life expectancy ≥ 12 weeks;
Exclusion Criteria
- •Pathologically confirmed fibrolamellar HCC, sarcomatoid HCC, cholangiocarcinoma and other components；
- •History of serious allergic diseases；
- •The toxicity of previous anti-tumor therapy has not been alleviated；
- •History of severe cardiovascular diseases within 6 months;
- •Current presence of uncontrolled pleural, pericardial, and peritoneal effusions;
- •History of allogeneic hematopoietic stem cell transplantation or allogeneic organ transplantation;
- •History of alcohol abuse, psychotropic substance abuse or drug abuse;
- •Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome;
- •Pregnant or lactating women;
- •Other conditions considered unsuitable for this study by the investigator.
Arms & Interventions
Cohort 1- combination treatment
Combination regimen：PM8002 combined with PM1009. The drugs are administered on the first day every 3 weeks (Q3W), until disease progression or intolerable toxicity or patient withdrawal or study discontinuation(Whichever occurs first).
Intervention: PM8002
Cohort 1- combination treatment
Combination regimen：PM8002 combined with PM1009. The drugs are administered on the first day every 3 weeks (Q3W), until disease progression or intolerable toxicity or patient withdrawal or study discontinuation(Whichever occurs first).
Intervention: PM1009
Cohort 2- combination treatment
Combination regimen：PM8002 combined with PM1009(low dose). The drugs are administered on the first day every 3 weeks (Q3W), until disease progression or intolerable toxicity or patient withdrawal or study discontinuation(Whichever occurs first).
Intervention: PM8002
Cohort 2- combination treatment
Combination regimen：PM8002 combined with PM1009(low dose). The drugs are administered on the first day every 3 weeks (Q3W), until disease progression or intolerable toxicity or patient withdrawal or study discontinuation(Whichever occurs first).
Intervention: PM1009
Cohort 3- monotherapy
PM8002 administered on the first day every 3 weeks (Q3W), until disease progression or intolerable toxicity or patient withdrawal or study discontinuation(Whichever occurs first).
Intervention: PM8002
Cohort 4
Combination regimen：atezolizumab combined with bevacizumab. The drugs are administered on the first day every 3 weeks (Q3W), until disease progression or intolerable toxicity or patient withdrawal or study discontinuation(Whichever occurs first).
Intervention: atezolizumab
Cohort 4
Combination regimen：atezolizumab combined with bevacizumab. The drugs are administered on the first day every 3 weeks (Q3W), until disease progression or intolerable toxicity or patient withdrawal or study discontinuation(Whichever occurs first).
Intervention: bevacizumab
Outcomes
Primary Outcomes
Objective response rate(ORR)
Time Frame: Up to approximately 2 years
ORR is the proportion of subjects with complete response (CR) or partial response (PR), based on RECIST v1.1.
Optimal dosing regimen of PM8002 in combination with PM1009
Time Frame: Up to approximately 2 years
To determine the dosing regimen of PM8002 in combination with PM1009
Treatment related adverse events (TRAEs)
Time Frame: Up to 30 days after last treatment
The incidence and severity of TRAEs graded according to NCI-CTCAE v5.0
Secondary Outcomes
- Objective response rate(ORR)(mRECIST)(Up to approximately 2 years)
- Disease control rate (DCR)(Up to approximately 2 years)
- Duration of response (DOR)(Up to approximately 2 years)
- Progression free survival (PFS)(Up to approximately 2 years)
- Overall survival (OS)(Up to approximately 2 years)
- Maximum observed concentration [Cmax](Up to 30 days after last treatment)
- Time to Cmax [Tmax](Up to 30 days after last treatment)
- Minimum observed concentration [Cmin](Up to 30 days after last treatment)
- Area under the concentration-time curve [AUC0-last](Up to 30 days after last treatment)
- AUC to the end of the dosing period(AUC0-tau)(Up to 30 days after last treatment)
- Apparent terminal elimination half-life (t1/2)(Up to 30 days after last treatment)
- Anti-drug antibody (ADA)(Up to 30 days after last treatment)