A Study Evaluating the Safety, Tolerance and Anti-tumor Activity of a Study Drug in Subjects With Advanced Solid Tumors

NCT04135261 | Completed Phase 1 FDA Drug

• 1 other identifier: 4003.1
• Study Type: interventional
• Target: 65
• Locations: 3 countries
• Sites: 17

Brief Summary

This is a study to evaluate the safety and tolerability of the study drug HBM4003, and to determine the maximum tolerated dose and/or recommended Phase 2 study dose of HBM4003. The study will also look at the anti-tumor activity of HBM4003.The study consists of 2 parts. In Part 1, patients are enrolled into different cohort doses in order to identify the appropriate recommended phase 2 dose (RP2D) or maximum tolerated dose (MTD). In Part 2, participants with metastatic/unresectable melanoma will receive the MTD and/or RP2D established in Part 1 of the study. In Part 1 and Part 2, participants will be administered treatment either once per week or once every 3 weeks. NOTE: Participants are no longer being recruited to this study.

Conditions

Advanced Solid Tumor

Keywords

advanced solid tumors

Outcome Measures

Primary Outcomes (2)

• Part 1: Proportion of subjects with Dose-Limiting Toxicity (DLT)

  Number of subjects who experience DLT events during 28 days (if on QW dosing schedule) or 21 days (if on Q3W dosing schedule)

  From Day 1 until disease progression or Day 28, whichever comes first

• Part 2: Objective Response Rate (ORR)

  Proportion of subjects with best overall response of complete response (CR) or partial response (PR) per RECIST 1.1

  Up to day 206 or until disease progression, unacceptable toxicity, withdrawal of consent, lack of treatment benefit, death or termination of study, whichever comes first.

Secondary Outcomes (20)

• Part 1: Objective Response Rate

  Up to day 206 or until disease progression, unacceptable toxicity, withdrawal of consent, lack of treatment benefit, death or termination of study, whichever comes first.

• Part 1: Duration of response

  Up to day 206 or until disease progression, unacceptable toxicity, withdrawal of consent, lack of treatment benefit, death or termination of study, whichever comes first.

• Part 1: Disease control rate

  Up to day 206 or until disease progression, unacceptable toxicity, withdrawal of consent, lack of treatment benefit, death or termination of study, whichever comes first.

• Part 1: Duration of disease control

  Up to day 206 or until disease progression, unacceptable toxicity, withdrawal of consent, lack of treatment benefit, death or termination of study, whichever comes first.

• Part 1: Tumor shrinkage (The percentage of patients with tumor shrinkage)

  Up to day 206 or until disease progression, unacceptable toxicity, withdrawal of consent, lack of treatment benefit, death or termination of study, whichever comes first.

Study Arms (2)

Part 1: Dose escalation

EXPERIMENTAL

QW - up to 4 (28 day) cycles of treatment (treatment administered 1x weekly) or Q3W - up to 6 (21 day) cycles of treatment (treatment administered 1x q3w) Dose for cohorts to be confirmed following consultation and approval by Safety Review Committee.

Drug: HBM4003

Part 2: Dose expansion

EXPERIMENTAL

Treatment administered at Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) established in Part 1, in specific tumor cohorts - Melanoma, HCC and RCC.

Drug: HBM4003

Interventions

HBM4003 DRUG

Intravenous (IV) administration

Part 1: Dose escalation; Part 2: Dose expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent form and willingness to comply with study requirements.
• Part 1 (Dose-escalation): Adult subject ≤ 75 years old with confirmed advanced solid tumors that have progressed after treatment with standard therapies, or for which no effective standard therapy is available, or the subject refuses or has a contraindication to standard therapy.
• Part 2 (Dose-expansion)
• Adult subjects 18 years and above.
• Melanoma Cohort:
• Histologically confirmed metastatic or unresectable melanoma that progressed during or after treatment with a PD-1 inhibitor (excluding bi-specific antibody) with CTLA-4 blocking function.
• Must have received at least one BRAF inhibitor with/without a MEK inhibitor if positive with BRAF V600-activating mutation.
• HCC Cohort:
• Histologically confirmed metastatic or unresectable hepatocellular carcinoma;
• Child-Pugh Score of 6 points or less (A5-A6);
• Patient with HBV infection will be allowed if he/she is receiving appropriate antiviral therapy for hepatitis B virus (HBV) according to institutional standard of care and HBV DNA level is \< 2000 UI/mL;
• Patient with HCV infection will be allowed if he/she is receiving appropriate antiviral therapy for hepatitis C virus (HCV) according to institutional standard of care and HCV antibody returns to negative;
• Have received at least one anti-VEGF treatment (either anti-VEGFR TKI or anti-VEGF monoclonal antibody) and/or anti-PD-(L)1 treatment.
• RCC Cohort:
• Histologically confirmed metastatic or unresectable renal cell cancer (including both clear cell and non-clear histology);

You may not qualify if:

• Part 1 and Part 2
• History of severe or not under well controlled allergic diseases, history of severe drug allergy, or are known to be allergic to macromolecular protein preparations or any component of the study drug.
• Receipt of anticancer medications or investigational drugs within the following intervals before the first administration of the study drug:
• CTLA-4 antibody any time prior to study drug administration;
• Any PD-1 or PD-L1 or Programmed cell death protein ligand 2 (PDL2)-directed antibody within 8 weeks of study drug administration;
• Any cancer vaccines within 3 months prior to first dose of study drug;
• Live vaccine within 4 weeks prior to first dose of study drug;
• Any other anticancer therapy within 2 weeks prior to first dose of study drug.
• Not yet recovered from surgery within 28 days prior to first dose of HBM4003 or (immune-related) toxicity related with previous treatment.
• Concomitant medication or treatments:
• Any concurrent chemotherapy, radiotherapy, immunotherapy, or biological therapy for cancer treatment. Concurrent use of hormones on a stable dose for non-cancer related conditions is acceptable. Androgen deprivation therapy (ADT) for advanced prostate cancers is acceptable. Local treatment of isolated non-target lesions for palliative intent is acceptable;
• Any traditional anti-tumor herbal medications;
• Receipt of red blood cells or platelets infusion, granulocyte colony stimulating factor (G-CSF) or granulocyte monocyte colony stimulating factor (GM-CSF) within 1 week of the first dose of HBM4003.
• Corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 2 weeks of study drug administration; Nasal spray, inhalation, topical corticosteroids or physiological doses of systemic corticosteroids are not included.
• Have other diseases that may affect the effectiveness and safety of the study drug, such as:

Sponsors & Collaborators

• Harbour BioMed US, Inc.: lead

Study Sites (17)

St. George Private Hospital, 1 South Street

Kogarah, New South Wales, 2217, Australia

Location

Macquarie University, 2 Technology Place

Macquarie, New South Wales, 2109, Australia

Location

Monash Health, Monash Medical Centre, 246 Clayton Road

Clayton, Victoria, 3168, Australia

Location

The Alfred Hospital, Commercial Road

Melbourne, Victoria, 3004, Australia

Location

Union Hospital affiliated to Tongji Medical College of HUST, Oncology Department, No. 1277 Jiefang Dadao

Wuhan, Hubei, 430022, China

Location

Yantai Yuhuangding Hospital, Urology Department, 8th Floor, No. 20 Donglu Road, Zhifu District

Yantai, Shandong, 264000, China

Location

The Second People's Hospital of Yibin, Oncology Department, No. 268 South Bank Nanguang Road, Xuzhou District

Yibin, Sichuan, 644000, China

Location

Zhejiang Cancer Hospital, Department of Head and Neck Medicine for Rare Diseases, No. 1, Banshan Road, Gongshu District

Hangzhou, Zhejiang, 310011, China

Location

Zhenjiang Cancer Hospital, Department of Interventional Therapy, No. 1, Banshan Road, Gongshu District

Hangzhou, Zhejiang, 310011, China

Location

Peking University First Hospital, Chemotherapy Department, No. 15 cheniandian Hutong, Annei Street, Dongcheng District

Beijing, 100034, China

Location

Cancer Hospital Chinese Academy of Medical Sciences, Oncology Department, No. 17 Panjiayuan Nanli, Chaoyang District

Beijing, 199921, China

Location

Hunan Cancer Hospital, Intervention Division, 83 Tongzipo Road, Yuelu District

Changsha, 410006, China

Location

Hunan Cancer Hospital, Urology Department, 83 Tongzipo Road, Yuelu District

Changsha, 410006, China

Location

Tianjin Medical University Cancer Institute and Hospital, Biotherapeutic Department, 17 / F, Block C, West Huan-Hu Rd., Ti Yuan Bei, Hexi District

Tianjin, 300060, China

Location

Xuzhou Central Hospital, Oncology Department, No. 199 Jiefang South Road, Quanshan District

Xuzhou, 221000, China

Location

Henan Cancer Hospital, Oncology Department, No. 127 Dongming Road, Jinshui District

Zhengzhou, 450000, China

Location

Queen Mary Hospital, Department of Medicine, 102 Pok Fu Lam Road

Hong Kong, Hong Kong

Location

Related Links

• FDA Safety Alerts and Recalls

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose escalation (Part 1) followed by Dose expansion (Part 2)

Study Record Dates

• First Submitted: October 15, 2019
• First Posted: October 22, 2019
• Study Start: September 24, 2019
• Primary Completion: January 17, 2023
• Study Completion: February 15, 2023
• Last Updated: April 18, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1); CN (12); AU (4)