A Clinical Trial to Evaluate of PM8002 Combined With PM1009 in Patients With First-line HCC

Phase 1

Not yet recruiting

• Conditions: HCC; Liver Cancer
• Interventions: Drug: PM8002; Drug: atezolizumab; Drug: PM1009; Drug: bevacizumab

• Registration Number: NCT06584071
• Lead Sponsor: Biotheus Inc.

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.

Study Timeline

• Study First Submitted: 2024-08-21
• Study First Submitted QC: 2024-09-02
• Study First Posted: 2024-09-04
• Status Verified: 2024-12
• Study Start: 2024-12
• Last Update Submitted: 2024-12-10
• Last Update Posted: 2024-12-16
• Primary Completion: 2026-10
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 140

Inclusion Criteria

1. Voluntary participation in clinical studies;
2. Male or female, aged ≥ 18 years;
3. Pathologically or clinically confirmed (according to AASLD), unresectable locally advanced and/or metastatic HCC;
4. Child-Pugh liver function score ≤7；
5. No prior systemic therapy for locally advanced or metastatic and/or unresectable HCC；
6. At least 1 measurable lesion ；
7. Adequate organ function；
8. ECOG score of 0 to 1；
9. Life expectancy ≥ 12 weeks;

Exclusion Criteria

1. Pathologically confirmed fibrolamellar HCC, sarcomatoid HCC, cholangiocarcinoma and other components；
2. History of serious allergic diseases；
3. The toxicity of previous anti-tumor therapy has not been alleviated；
4. History of severe cardiovascular diseases within 6 months;
5. Current presence of uncontrolled pleural, pericardial, and peritoneal effusions;
6. History of allogeneic hematopoietic stem cell transplantation or allogeneic organ transplantation;
7. History of alcohol abuse, psychotropic substance abuse or drug abuse;
8. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome;
9. Pregnant or lactating women;
10. Other conditions considered unsuitable for this study by the investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1- combination treatment	PM1009	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).
Cohort 3- monotherapy	PM8002	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).
Cohort 1- combination treatment	PM8002	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).
Cohort 2- combination treatment	PM8002	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).
Cohort 2- combination treatment	PM1009	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).
Cohort 4	atezolizumab	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).
Cohort 4	bevacizumab	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).

Primary Outcome Measures

Name	Time	Method
Objective response rate(ORR)	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	Up to approximately 2 years	To determine the dosing regimen of PM8002 in combination with PM1009
Treatment related adverse events (TRAEs)	Up to 30 days after last treatment	The incidence and severity of TRAEs graded according to NCI-CTCAE v5.0

Secondary Outcome Measures

Name	Time	Method
Objective response rate(ORR)(mRECIST)	Up to approximately 2 years	ORR is the proportion of subjects with complete response (CR) or partial response (PR), based on mRECIST
Disease control rate (DCR)	Up to approximately 2 years	DCR is defined as the proportion of subjects with complete response (CR), partial response (PR) or stable disease (SD) based on RECIST v1.1 and mRECIST
Duration of response (DOR)	Up to approximately 2 years	DOR is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first
Progression free survival (PFS)	Up to approximately 2 years	PFS is defined as the time from the start of treatment until the first documentation of disease progression or death due to any cause, whichever occurs first
Overall survival (OS)	Up to approximately 2 years	OS is the time from the date of randomization or first dosing date to death due to any cause
Maximum observed concentration [Cmax]	Up to 30 days after last treatment	To evaluate the Cmax of Combination regimen .
Time to Cmax [Tmax]	Up to 30 days after last treatment	To evaluate the Tmax of Combination regimen .
Minimum observed concentration [Cmin]	Up to 30 days after last treatment	To evaluate the Cmin of Combination regimen .
Area under the concentration-time curve [AUC0-last]	Up to 30 days after last treatment	To evaluate the AUC0-last of Combination regimen .
AUC to the end of the dosing period(AUC0-tau)	Up to 30 days after last treatment	To evaluate the AUC0-tau of Combination regimen .
Apparent terminal elimination half-life (t1/2)	Up to 30 days after last treatment	To evaluate the t1/2 of Combination regimen .
Anti-drug antibody (ADA)	Up to 30 days after last treatment	To evaluate the incidence of ADA to PM8002