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

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

This study to evaluate the preliminary efficacy, safety and pharmacokinetics of PM8002 combined with PM1009 in Patients with first-line Hepatocellular Carcinoma.

Study Overview

• Status: Not yet recruiting
• Conditions: HCC; Liver Cancer
• Intervention / Treatment: Drug: PM8002; Drug: PM1009; Drug: atezolizumab; Drug: bevacizumab

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 Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Xuelian Xing; Phone Number: +86 021 32120207; Email: xing.xl@biotheus.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Drug: PM8002; PM8002 via IV infusion, Q3W; Drug: PM1009; PM8002 via IV infusion, Q3W
Experimental: 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).	Drug: PM8002; PM8002 via IV infusion, Q3W; Drug: PM1009; PM8002 via IV infusion, Q3W
Experimental: 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).	Drug: PM8002; PM8002 via IV infusion, Q3W
Active Comparator: 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).	Drug: atezolizumab; atezolizumab,1200mg, via IV infusion, Q3W; Drug: bevacizumab; bevacizumab,15mg/kg, via IV infusion, Q3W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment related adverse events (TRAEs)	The incidence and severity of TRAEs graded according to NCI-CTCAE v5.0	Up to 30 days after last treatment
Objective response rate(ORR)	ORR is the proportion of subjects with complete response (CR) or partial response (PR), based on RECIST v1.1.	Up to approximately 2 years
Optimal dosing regimen of PM8002 in combination with PM1009	To determine the dosing regimen of PM8002 in combination with PM1009	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate(ORR)(mRECIST)	ORR is the proportion of subjects with complete response (CR) or partial response (PR), based on mRECIST	Up to approximately 2 years
Disease control rate (DCR)	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	Up to approximately 2 years
Duration of response (DOR)	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	Up to approximately 2 years
Progression free survival (PFS)	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	Up to approximately 2 years
Overall survival (OS)	OS is the time from the date of randomization or first dosing date to death due to any cause	Up to approximately 2 years
Maximum observed concentration [Cmax]	To evaluate the Cmax of Combination regimen .	Up to 30 days after last treatment
Time to Cmax [Tmax]	To evaluate the Tmax of Combination regimen .	Up to 30 days after last treatment
Minimum observed concentration [Cmin]	To evaluate the Cmin of Combination regimen .	Up to 30 days after last treatment
Area under the concentration-time curve [AUC0-last]	To evaluate the AUC0-last of Combination regimen .	Up to 30 days after last treatment
AUC to the end of the dosing period(AUC0-tau)	To evaluate the AUC0-tau of Combination regimen .	Up to 30 days after last treatment
Apparent terminal elimination half-life (t1/2)	To evaluate the t1/2 of Combination regimen .	Up to 30 days after last treatment
Anti-drug antibody (ADA)	To evaluate the incidence of ADA to PM8002	Up to 30 days after last treatment

Collaborators and Investigators

• Sponsor: Biotheus Inc.
• Investigators: Principal Investigator: Jia Fan, Zhong Shan Hospital, Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: August 21, 2024
• First Submitted That Met QC Criteria: September 2, 2024
• First Posted (Actual): September 4, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 10, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: HCC; first line; PM1009; PM8002
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Liver Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab; Atezolizumab
• Other Study ID Numbers: PM80021009-AB001C-HCC-R

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data will be published or presented for publications (poster, abstract,articles or papers) or any presentations
• IPD Sharing Time Frame: After the trial completed
• IPD Sharing Access Criteria: NCI is committed to sharing data in accordance with NIH policy.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No