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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04135261




Registration number
NCT04135261
Ethics application status
Date submitted
15/10/2019
Date registered
22/10/2019
Date last updated
18/04/2023

Titles & IDs
Public title
A Study Evaluating the Safety, Tolerance and Anti-tumor Activity of a Study Drug in Subjects With Advanced Solid Tumors
Scientific title
A Phase 1 Open-label, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of HBM4003 in Subjects With Advanced Solid Tumors
Secondary ID [1] 0 0
4003.1
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumor 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - HBM4003

Experimental: Part 1: Dose escalation - 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.

Experimental: Part 2: Dose expansion - 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.


Treatment: Drugs: HBM4003
Intravenous (IV) administration
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1: Proportion of subjects with Dose-Limiting Toxicity (DLT)
Timepoint [1] 0 0
From Day 1 until disease progression or Day 28, whichever comes first
Primary outcome [2] 0 0
Part 2: Objective Response Rate (ORR)
Timepoint [2] 0 0
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 outcome [1] 0 0
Part 1: Objective Response Rate
Timepoint [1] 0 0
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 outcome [2] 0 0
Part 1: Duration of response
Timepoint [2] 0 0
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 outcome [3] 0 0
Part 1: Disease control rate
Timepoint [3] 0 0
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 outcome [4] 0 0
Part 1: Duration of disease control
Timepoint [4] 0 0
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 outcome [5] 0 0
Part 1: Tumor shrinkage (The percentage of patients with tumor shrinkage)
Timepoint [5] 0 0
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 outcome [6] 0 0
Part 1: Cmax (Maximum serum concentration)
Timepoint [6] 0 0
Up to 80 days after end of treatment
Secondary outcome [7] 0 0
Part 1: Tmax (Time to reach maximum serum concentration)
Timepoint [7] 0 0
Up to 80 days after end of treatment
Secondary outcome [8] 0 0
Part 1: AUC0-inf (Area under the serum concentration versus time curve from time zero to infinity
Timepoint [8] 0 0
Up to 80 days after end of treatment
Secondary outcome [9] 0 0
Part 1: Vss (Volume of distribution at steady state)
Timepoint [9] 0 0
Up to 80 days after end of treatment
Secondary outcome [10] 0 0
Part 1: AUC0-tau (Area under the serum concentration versus time curve from time zero to the dosing interval tau
Timepoint [10] 0 0
Up to 80 days after end of treatment
Secondary outcome [11] 0 0
Part 1: t1/2 (Terminal half-life)
Timepoint [11] 0 0
Up to 80 days after end of treatment
Secondary outcome [12] 0 0
Part 1: Clearance (CL)
Timepoint [12] 0 0
Up to 80 days after end of treatment
Secondary outcome [13] 0 0
Part 1: Cmin (Minimum serum concentration)
Timepoint [13] 0 0
Up to 80 days after end of treatment
Secondary outcome [14] 0 0
Part 1: Rac(Cmax)
Timepoint [14] 0 0
Up to 80 days after end of treatment
Secondary outcome [15] 0 0
Part 1: Rac(AUC0-tau)
Timepoint [15] 0 0
Up to 80 days after end of treatment
Secondary outcome [16] 0 0
Part 2: Disease control rate
Timepoint [16] 0 0
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 outcome [17] 0 0
Part 2: Duration of objective response
Timepoint [17] 0 0
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 outcome [18] 0 0
Part 2: Objective Response Rate
Timepoint [18] 0 0
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 outcome [19] 0 0
Part 2: Duration of disease control
Timepoint [19] 0 0
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 outcome [20] 0 0
Part 2: Tumor shrinkage (The percentage of patients with tumor shrinkage)
Timepoint [20] 0 0
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.

Eligibility
Key inclusion criteria
- 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:

1. 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.

2. Must have received at least one BRAF inhibitor with/without a MEK inhibitor if
positive with BRAF V600-activating mutation.

HCC Cohort:

1. Histologically confirmed metastatic or unresectable hepatocellular carcinoma;

2. Child-Pugh Score of 6 points or less (A5-A6);

3. 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;

4. 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;

5. 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:

1. Histologically confirmed metastatic or unresectable renal cell cancer (including both
clear cell and non-clear histology);

2. Subjects with clear cell RCC must have failed at least 1 anti-VEGFR TKI treatment
and/or anti-PD(L)1 treatment;

3. For subjects with non-clear cell RCC (e.g. PRCC), treatment naive is permitted.

- Must have at least one measurable lesion based on Response Evaluation Criteria in
Solid Tumors (RECIST) 1.1.

- Willing to undergo tumor biopsy unless determined medically unsafe or not
feasible.

- For subjects whose last treatment was immunotherapy, must have disease
progression confirmed at least 4 weeks after the initial radiographic evidence of
progression;

- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.

- Adequate organ and bone marrow function.

- Females of childbearing potential may participate provided they agree to practice
abstinence; and, if heterosexually active, agree to use at least 2 highly
effective contraceptive methods throughout the study and for 3 months following
the last dose of HBM4003; and have a negative serum pregnancy test.

- Females of non-childbearing potential must be post-menopausal or have been
surgically sterilized.

- Male subjects with a female partner of childbearing potential must agree to
practice abstinence or to use a physician-approved contraceptive method
throughout the study and for 3 months following the last dose of study drug.

- Life expectancy of =12 weeks.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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:

1. CTLA-4 antibody any time prior to study drug administration;

2. Any PD-1 or PD-L1 or Programmed cell death protein ligand 2 (PDL2)-directed
antibody within 8 weeks of study drug administration;

3. Any cancer vaccines within 3 months prior to first dose of study drug;

4. Live vaccine within 4 weeks prior to first dose of study drug;

5. 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:

1. 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;

2. Any traditional anti-tumor herbal medications;

3. 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.

4. 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:

1. Known brain metastases or other central nervous system metastases that is either
symptomatic or untreated, that requires concurrent treatment;

2. Active infection requiring treatment with antibiotics within 14 days prior to
first dose of HBM4003;

3. Known history of infection with human immunodeficiency virus (HIV) or known
acquired immunodeficiency syndrome (AIDS), human T lymphotropic virus 1,
hepatitis B virus, or active hepatitis C virus;

4. Suspected autoimmune disease, including but not limited to inflammatory bowel
disease, autoimmune hepatitis, Guillain-Barre syndrome.

5. Known primary immunodeficiency;

6. Clinically significant gastrointestinal disorders (e.g. diarrhea with significant
clinical meaning), active gastrointestinal bleeding, or a history of
gastrointestinal perforation, acute diverticulitis, intra-abdominal abscess or
gastrointestinal obstruction;

7. Have received allogeneic organ transplantation or allogeneic hematopoietic stem
cell transplantation, or have received autologous hematopoietic stem cell
transplantation within 3 months prior to the first dose of study drug.

8. Subjects with medically confirmed autoimmune coeliac disease are to be excluded.
Patients with so-called gluten intolerance or other conditions labelled "coeliac
disease" which are not autoimmune in nature and which are well controlled by diet
should be medically confirmed as non-autoimmune "coeliac disease" and can be
considered for study.

- Subjects with major cardiovascular disease.

- History of other uncured malignant diseases, except for non-melanoma skin cancer in
situ, superficial bladder cancer, cervical cancer in situ that has been curatively
resected, and localized prostate cancer managed by active surveillance.

- Pregnant or breastfeeding women.

- Have experienced immune-related GI adverse events on any prior immunotherapy or
toxicity that led to permanent discontinuation of prior immunotherapy.

- Severe cirrhosis, hepatic atrophy, portal hypertension.

- Main portal vein thrombosis present on imaging.

- Any prior or current clinically significant ascites (moderate to massive with
significantly abnormal liver function).

- Any history of hepatic encephalopathy within 12 months prior to randomization or
require medications to prevent or control encephalopathy.

- Subjects weighting < 30 kg.

- Active or prior documented GI bleeding (e.g. esophageal varices or ulcer bleeding)
within 12 months.

Additional criterial for HCC cohort:

- Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.

- Prior liver transplantation.

- HBV and HCV co-infection, HBV and HEV co-infection, HBV and HDV co-infection.

Other protocol-defined inclusion/exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
24/09/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
15/02/2023
Sample size
Target
Accrual to date
Final
65
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
St. George Private Hospital, 1 South Street - Kogarah
Recruitment hospital [2] 0 0
Macquarie University, 2 Technology Place - Macquarie
Recruitment hospital [3] 0 0
Monash Health, Monash Medical Centre, 246 Clayton Road - Clayton
Recruitment hospital [4] 0 0
The Alfred Hospital, Commercial Road - Melbourne
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
2109 - Macquarie
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
China
State/province [1] 0 0
Hubei
Country [2] 0 0
China
State/province [2] 0 0
Shandong
Country [3] 0 0
China
State/province [3] 0 0
Sichuan
Country [4] 0 0
China
State/province [4] 0 0
Zhejiang
Country [5] 0 0
China
State/province [5] 0 0
Beijing
Country [6] 0 0
China
State/province [6] 0 0
Changsha
Country [7] 0 0
China
State/province [7] 0 0
Tianjin
Country [8] 0 0
China
State/province [8] 0 0
Xuzhou
Country [9] 0 0
China
State/province [9] 0 0
Zhengzhou
Country [10] 0 0
Hong Kong
State/province [10] 0 0
Hong Kong

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Harbour BioMed US, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04135261
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04135261