A Study of Injection HB0025 in Patients With Advanced Solid Tumors

• ClinicalTrials.gov Identifier: NCT04678908
• Recruitment Status: Recruiting
• First Posted: December 22, 2020
• Last Update Posted: April 8, 2021
• Sponsor: Huabo Biopharm Co., Ltd.
• Information provided by (Responsible Party): Huabo Biopharm Co., Ltd.

Study Description

Brief Summary:

This is a multicenter, open-label, dose escalation and expansion study. During the study, subjects will be evaluated for safety, toxicity, tolerability, PK/PD, immunogenicity, biomarkers, and antitumor activity of HB0025. The phase I study will enroll up to 78 subjects with advanced solid tumors who have progressed on or after standard of care therapy and for whom there is no further treatment available that in the judgement of the patient's physician would be beneficial. One cycle is defined as 28 days.

Condition or disease	Intervention/treatment	Phase
Health, Subjects	Drug: HB0025	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 54 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: A Phase 1, Multicenter, Open-label, Dose-escalation and Dose-expansion Study of the Safety and Pharmacokinetics of HB0025 in Patients With Advanced Solid Tumors
• Actual Study Start Date: March 8, 2021
• Estimated Primary Completion Date: October 22, 2021
• Estimated Study Completion Date: December 22, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: HB0025; HB0025 IV every 2 weeks (q2w)	Drug: HB0025; Patients will be assigned to dose regimens in the order of enrollment, and they will receive their assigned fixed dose of HB0025 via intravenous infusion.; Other Name: Recombinant Humanized Anti-PD-L1 Monoclonal Antibody-VEGFR1 Fusion Protein

Outcome Measures

Primary Outcome Measures :

1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 Incidence, nature, relatedness, and severity of AEs. [ Time Frame: 240 Days ]
2. Maximum tolerated dose (MTD) and/or Phase 2 dose (RP2D) for HB0025. [ Time Frame: 240 Days ]

Secondary Outcome Measures :

1. Area Under concentration-time Curve (AUC) of HB0025. [ Time Frame: 240 Days ]
2. Maximum serum concentration (Cmax) of HB0025. [ Time Frame: 240 Days ]
3. Clearance (CL) of HB0025. [ Time Frame: 240 Days ]
4. Anti-drug antibody (ADA) and neutralizing antibodies (Nab) of HB0025. [ Time Frame: 240 Days ]
5. Overall response rate (ORR). [ Time Frame: Up to 2 years ]
6. Disease control rate (DCR). [ Time Frame: Up to 2 years ]
7. progression-free survival (PFS). [ Time Frame: Up to 2 years ]
8. Duration of response (DOR). [ Time Frame: Up to 2 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Male or female. Age ≥ 18 years.
2. Willing and able to provide signed and dated informed consent prior to any study-related procedures and willing and able to comply with all study procedures.
3. Patients with histologically or cytologically confirmed advanced malignant solid tumor who have received or been intolerant of all standard therapies thought to confer clinical benefit.
4. Dose escalation stage: Evaluable disease per RECIST v1.1 for solid tumors; Radiographic disease assessment at baseline can be performed up to 28 days prior to the first dose.
5. Dose expansion stage: At least one measurable tumor lesion as per RECIST criteria v1.1 defined as having at least one dimension with a minimum size of 10 mm in the longest diameter by CT or MRI scan for non-nodal lesions or ≥15 mm in short axis for nodal lesions. Radiographic disease assessment at baseline can be performed up to 28 days prior to the first dose.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.
7. Life expectancy ≥3 months.

8. Adequate hepatic function as evidenced by meeting all the following requirements:

   1. Total bilirubin ≤ 1.5 × upper limit of normal (ULN).
   2. AST and ALT ≤ 2.5 × ULN; AST or ALT ≤ 5 × ULN if liver metastases are present.
9. Serum creatinine (Scr) < 1.5 × ULN and calculated creatinine clearance (CrCL) > 40 mL/min (Cockroft-Gault Equation).

10. Hematological function defined as:

    1. Absolute neutrophil count ≥1,500/µL without growth factor support within 2 weeks prior to the first dose of HB0025.
    2. Hemoglobin ≥ 9 g/dL without transfusion or erythropoietin within 2 weeks prior to the first dose of HB0025.
    3. Platelet count ≥ 75,000/µL without transfusion or recombinant human thrombopoietin within 2 weeks prior to the first dose of HB0025.
11. Coagulation: International Normalized Ratio (INR)≤1.6 (unless receiving anticoagulation therapy). Subjects on full-dose oral anticoagulation must be on a stable dose (minimum duration 14 days). If receiving warfarin, the subject must have an INR≤3.0 and no active bleeding (ie, no bleeding within 14 days prior to first dose of study drug). Subjects on low molecular weight heparin will be allowed. Subjects must have no active bleeding or clinically significant bleeding within 14 days prior to first dose of study drug.
12. Recovery, to Grade 0-1, from adverse events related to prior anticancer therapy except alopecia, < Grade 2 sensory neuropathy, lymphopenia, and endocrinopathies controlled with hormone replacement therapy.
13. All patients will be required to provide (if available) archived paraffin blocks or at least 10 unstained slides prior to study entry. Patients who do not have available archival tissue will be asked (optional) to provide fresh tissue from core-needle or punch biopsy.

Exclusion Criteria:

Patients who meet any of the following criteria cannot be enrolled:

1. Symptomatic central nervous system metastases; patients with asymptomatic CNS metastases who are radiologically and neurologically stable > 4 weeks following CNS directed therapy, and are on a stable or decreasing dose of corticosteroids equivalent to < 10 mg prednisone/day for at least 2 weeks prior to study treatment are eligible for study entry.
2. Active autoimmune disease or history of autoimmune disease requiring systemic therapy < 2 years prior to screening except hypothyroidism, vitiligo, Grave's disease, Hashimoto's disease, or Type I diabetes. Patients with childhood asthma or atopy that has not been active in the 2 years prior to study screening are eligible.
3. History of Grade 3-4 immune-related adverse events (irAEs) or irAEs requiring discontinuation of prior therapies, (except for grade 3 endocrinopathy that is managed with hormone replacement therapy).
4. Use of systemic corticosteroids in a dose equivalent to > 10 mg/day of prednisone or other immunosuppressive agent < 2 weeks prior to screening; the use of topical, intraocular, intra-articular, intranasal or inhaled corticosteroids (systemic absorption is low) will be allowed to prevent (e.g., allergy to contrast agents) or treat non-autoimmune condition (e.g. delayed hypersensitivity caused by exposure to allergens).
5. Cerebrovascular accident (CVA), Transient ischemic attack (TIA), myocardial infarction (MI), unstable angina, or New York Heart Association (NYHA) class III or IV heart failure < 6 months of study entry; mean ECG QT-interval corrected according to Fridericia's formula (QTcF) > 470 milliseconds (ms) (males) or > 480 ms (females) obtained from three ECGs; uncontrolled arrhythmia < 3 months of study entry. Patients with rate-controlled arrhythmias may be eligible for study entry at discretion of the Investigator.
6. Uncontrolled diabetes mellitus with hemoglobin A1c > 8%.
7. Subjects who have received previous simultaneous therapy with a PD-1 pathway inhibitor and a VEGF inhibitor.
8. Anticancer therapy or radiation < 5 half-lives or 4 weeks (whichever is shorter) prior to study entry; palliative radiotherapy to a single area < 2 weeks prior to study screening is permitted. Measurable lesions cannot be previously irradiated unless they have demonstrated growth after radiation therapy (RT).
9. Prior stem cell, bone marrow or solid organ transplant.
10. Concurrent malignancy < 5 years prior to entry other than adequately treated cervical carcinoma-in-situ, localized squamous cell cancer of the skin, basal cell carcinoma, localized prostate cancer, ductal carcinoma in situ of the breast, or < T1 urothelial carcinoma. Patients with prostate cancer that is under active surveillance are eligible.

11. Any of the following infections. a) Active infection requiring intravenous therapy < 2 weeks prior to screening. b) Active tuberculosis (via medical history).

    c) Patients infected with the HIV virus will be eligible if their CD4 count is > 350 cells/mm3 and the patient is on anti-retroviral therapy with an HIV viral load that is below the level of detection. d) Active hepatitis B or C. HBV carriers without active disease (HBV DNA titer < 1000 cps/mL or 200 IU/mL), or cured Hepatitis C (negative HCV RNA test) may be enrolled.

12. Major surgery < 4 weeks or minor surgery < 2 weeks prior to screening; wound must be fully healed.
13. History of severe allergic reactions, Grade 3-4 allergic reaction to treatment with another monoclonal antibody, or known to be allergic to protein drugs or recombinant proteins or excipients in HB0025 drug formulation.
14. Live virus vaccines < 30 days prior to screening.
15. Pregnant or breast-feeding females.prevent (e.g., allergy to contrast agents) or treat non-autoimmune condition (e.g. delayed hypersensitivity caused by exposure to allergens).
16. Any investigational agents or study drugs from a previous clinical study within 30 days of the first dose of study treatment.
17. Any other serious underlying medical condition (e.g. active gastric ulcer, uncontrolled seizures, cerebrovascular incidents, gastrointestinal bleeding, severe signs and symptoms of coagulation and clotting disorders, cardiac conditions), or psychiatric, psychological, familial condition or geographical location that, in the judgment of the Investigator, may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications.
18. Women of childbearing potential who do not consent to use acceptable methods of birth control during treatment and for an additional 90 days after the last administration of HB0025.
19. Men with a partner of childbearing potential who do not consent to use acceptable methods of birth control during treatment and for an additional 90 days after the last administration of HB0025.
20. Positive COVID-19 qRT-PCR and/or serology test result during screening;
21. Subjects with a history of arterial or deep venous thrombosis within 3 months before enrollment, or patients with evidence or history of bleeding tendency within 2 months before enrollment, regardless of severity.
22. Severe dyspnea or pulmonary dysfunction or need for continuous supportive oxygen inhalation.
23. Skin wound, surgical site, wound site, mucosal ulcer or fracture not completely healed;
24. Conditions that may cause gastrointestinal bleeding or perforation (such as duodenal ulcer, intestinal obstruction, Crohn's disease, ulcerative colitis, large-scale gastrectomy, etc.); patients with previous history of intestinal perforation and intestinal fistula but not cured after surgical treatment; esophageal and gastric varices.
25. Subjects received immune modulators treatment, including but not limited to cyclosporine and tacrolimus, within 2 weeks before enrollment.
26. Inability to comply with study and follow-up procedures.
27. Patients who have history of interstitial lung disease or non-infectious pneumonitis except if due to radiation therapy; such patients should be discussed with the Medical Monitor before enrollment.
28. Subjects who in the judgement of the Investigator are not suited to participate in this trial.
29. Uncontrolled hypertension defined as systolic blood pressure >150 mmHg and diastolic blood pressure >80 mmHg.
30. Patients with > 2+ protein on urine dipstick should have a 24-hour urine collection; Patients with ≥ 2 g of protein in the urine on 24-hour collection are ineligible for study entry.

Contacts and Locations

Contacts

Contact: Anthony Tolcher; 210-580-9500; atolcher@nextoncology.com

Locations

United States, Texas

NEXT Oncology; Recruiting

San Antonio, Texas, United States, 78229

Contact: Anthony Tolcher, MD 210-580-9500 atolcher@nextoncology.com

China, Shanghai

Fudan University Shanghai Cancer Center; Not yet recruiting

Shanghai, Shanghai, China, 201210

Contact: Jian Zhang, MD Syner2000@163.com

Sponsors and Collaborators

Huabo Biopharm Co., Ltd.

More Information

• Responsible Party: Huabo Biopharm Co., Ltd.
• ClinicalTrials.gov Identifier: NCT04678908
• Other Study ID Numbers: HB0025-01
• First Posted: December 22, 2020
• Last Update Posted: April 8, 2021
• Last Verified: March 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No