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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/NCT05102214




Registration number
NCT05102214
Ethics application status
Date submitted
29/09/2021
Date registered
1/11/2021
Date last updated
8/08/2023

Titles & IDs
Public title
HLX301 (TIGIT×PDL1 Bispecific) in Patients With Locally Advanced or Metastatic Solid Tumors
Scientific title
A Phase 1/2 Study of HLX301, A Recombinant Humanized Anti-PDL1 and Anti-TIGIT Bispecific Antibody, in Patients With Locally Advanced or Metastatic Solid Tumors
Secondary ID [1] 0 0
HLX301-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Locally Advanced or Metastatic Solid Tumors 0 0
Non-small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - HLX301

Experimental: Phase 1a dose-escalation stage - Phase 1a uses the Bayesian optimal interval (BOIN) design, to investigate the safety and determine the MTD of HLX301. Six dose levels of 0.25 mg/kg, 1 mg/kg, 2.5 mg/kg, 5 mg/kg, 10 mg/kg, and 15 mg/kg are planned for dose finding. Intra-patient dose escalation is not permitted. Enrollment will continue until a maximum of 30 patients are enrolled.

Experimental: Phase 1b dose-expansion stage - Patients with NSCLC will be enrolled in two expansion cohorts, at doses equal to or lower than the MTD, to better characterize the safety, tolerability, PK variability, and preliminary efficacy of single-agent HLX301. Phase 1b dose expansion will include 20 per-protocol treated patients, as defined above, in each of the two expansion cohorts.

Experimental: Phase 2 clinical expansion stage: Cohort A - 20 per-protocol treated patients with non-small cell lung cancer (NSCLC), with PD-L1 expression, progression after one or two prior systemic anti-tumor regimens, and who have failed or are intolerant to standard therapy, or for whom no standard therapy is available, will be enrolled and treated in phase 2 at RP2D.

Experimental: Phase 2 clinical expansion stage: Cohort B - 20 per-protocol treated patients with gastric/esophagogastric junction adenocarcinoma (GC/EGJ), with PD-L1 expression, progression after one or two prior systemic anti-tumor regimens, and who have failed or are intolerant to standard therapy, or for whom no standard therapy is available, will be enrolled and treated in phase 2 at RP2D.

Experimental: Phase 2 clinical expansion stage: Cohort C - 20 per-protocol treated patients with head and neck squamous cell carcinoma (HNSCC), with PD-L1 expression, progression after one or two prior systemic anti-tumor regimens, and who have failed or are intolerant to standard therapy, or for whom no standard therapy is available, will be enrolled and treated in phase 2 at RP2D.

Experimental: Phase 2 clinical expansion stage: Cohort D - 20 per-protocol treated patients with urothelial carcinoma (UC), with PD-L1 expression, progression after one or two prior systemic anti-tumor regimens, and who have failed or are intolerant to standard therapy, or for whom no standard therapy is available, will be enrolled and treated in phase 2 at RP2D.


Treatment: Drugs: HLX301
A Recombinant Humanized Anti-PDL1 and Anti-TIGIT Bispecific Antibody, HLX301 will be administered as a single intravenous (IV) infusion on Day 1 in each 14-day cycle
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1a: Safety assessments in patients receiving the trial drug
Timepoint [1] 0 0
2 years
Primary outcome [2] 0 0
Phase 1a: The proportion of patients experiencing dose limiting toxicity (DLT) events
Timepoint [2] 0 0
From baseline to the end of cycle 2 (28 days)
Primary outcome [3] 0 0
Phase 1a: The maximum tolerated dose (MTD) of HLX301
Timepoint [3] 0 0
From baseline to the end of cycle 2 (28 days)
Primary outcome [4] 0 0
Phase 1b: Recommended phase 2 dose (RP2D)
Timepoint [4] 0 0
From baseline to 48 weeks after first infusion
Primary outcome [5] 0 0
Phase 2: Objective response rate (ORR) defined as achieving a complete response or partial response as determined by the investigator according to RECIST v1.1
Timepoint [5] 0 0
2 years
Primary outcome [6] 0 0
Phase 2: Disease control rate (DCR) defined as achieving the complete response, partial response, or stable disease as determined by the investigator according to RECIST v1.1
Timepoint [6] 0 0
2 years
Primary outcome [7] 0 0
Phase 2: Duration of response (DOR) defined as the time from the first occurrence of a documented ORR to disease progression, as determined by the investigator according to RECIST v1.1
Timepoint [7] 0 0
2 years
Secondary outcome [1] 0 0
Phase 1a: The pharmacokinetic parameters of HLX301: Peak concentration (Cmax, Cmax,ss)
Timepoint [1] 0 0
2 years
Secondary outcome [2] 0 0
Phase 1a: The pharmacokinetic parameters of HLX301: Time to peak (Tmax, Tmax,ss)
Timepoint [2] 0 0
2 years
Secondary outcome [3] 0 0
Phase 1a: The pharmacokinetic parameters of HLX301: Area under the concentration-time curve (AUC0-inf, AUC0-t, AUCss)
Timepoint [3] 0 0
2 years
Secondary outcome [4] 0 0
Phase 1a: The pharmacokinetic parameters of HLX301: Elimination half-life (t1/2)
Timepoint [4] 0 0
2 years
Secondary outcome [5] 0 0
Phase 1a: The pharmacokinetic parameters of HLX301: Clearance (CL, CLss)
Timepoint [5] 0 0
2 years
Secondary outcome [6] 0 0
Phase 1a: The pharmacokinetic parameters of HLX301: Volume of distribution (Vz, Vss)
Timepoint [6] 0 0
2 years
Secondary outcome [7] 0 0
Phase 1a: The pharmacodynamic profiles of HLX301 as determined by receptor occupancy of HLX301 on circulating T cells
Timepoint [7] 0 0
2 years
Secondary outcome [8] 0 0
Phase 1a: The incidence of treatment-emergent anti-drug antibodies (ADA) of HLX301
Timepoint [8] 0 0
2 years
Secondary outcome [9] 0 0
Phase 1b: The preliminary efficacy as determined by ORR
Timepoint [9] 0 0
2 years
Secondary outcome [10] 0 0
Phase 1b: The preliminary efficacy as determined by DCR
Timepoint [10] 0 0
2 years
Secondary outcome [11] 0 0
Phase 1b: The preliminary efficacy as determined by DOR
Timepoint [11] 0 0
2 years
Secondary outcome [12] 0 0
Phase 2: The safety profile
Timepoint [12] 0 0
2 years
Secondary outcome [13] 0 0
Phase 2: To investigate the correlation between PD-L1 expression levels and anti-tumor activity of HLX301 in patients with NSCLC, GC/EJC, HNSCC and UC
Timepoint [13] 0 0
2 years

Eligibility
Key inclusion criteria
- 1. Patients who meet the following criteria will be enrolled:

1. Phase 1a dose escalation: patients must have histologically or cytologically
confirmed malignant solid tumors which are advanced or metastatic, have failed
prior standard treatment, and be intolerant or ineligible for standard therapy
(with the exception of hepatocellular carcinoma, which meets diagnostic criteria
by dynamic CT/MRI).

2. Phase 1b dose expansion: patients must have a histological or cytological
diagnosis of Non-Small Cell Lung Cancer which is advanced or metastatic, have
failed prior standard treatment, and be intolerant or ineligible for standard
therapy.

3. Phase 2 clinical expansion: patients must have histological confirmed or
cytological diagnosis of PD-L1 expressing, i.e., TPS =1% non-small cell lung
cancer, CPS =1 gastric/esophagogastric junction adenocarcinoma, CPS =1 head and
neck squamous cell carcinoma, or CPS =10 urothelial carcinoma, have failed at
least one or two prior systemic anti-tumor regimens, and be intolerant or
ineligible for standard therapy.

- 2. Age = 18 years, or legally an adult as per local regulations.

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

- 4. Measurable disease according to RECIST Version 1.1

- 5. Able to provide informed consent.

- 6. A life expectancy longer than three months.

- 7. Adequate hematologic parameters, defined as white blood cell count = 3000/mm3 and
absolute neutrophil counts = 1500/mm3; hemoglobin= 10 gm/dL; platelet count =
100,000/mm3 without platelet transfusion within 14 days.

- 8. Adequate hepatic function, defined as serum albumin = 3.0 g/dL; serum total
bilirubin = 1.5x upper limit of normal (ULN); serum aspartate transaminase (AST) and
alanine transaminase (ALT) = 3.0 x ULN (AST and ALT = 5 × ULN for patients with known
liver metastasis or primary hepatocellular carcinoma); Child-Pugh score A in HCC.

- 9. Adequate renal function, defined as serum creatinine = 1.5x upper limit of normal
(ULN).

- 10. Adequate cardiac function defined as left ventricular ejection fraction (LVEF) =
50% measured by cardiac ultrasound or MUGA scan; normal ECG or ECG without any
clinically significant findings.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 1. Received prior anti-TIGIT therapy.

- 2. Patients who still have persistent = grade 2 toxicities from prior therapies.

- 3. Concurrent unstable or uncontrolled medical conditions including, but not limited
to, the following:

1. Ongoing or active systemic infections requiring antibiotic treatment

2. Clinically significant arrhythmia, unstable angina pectoris, class III or IV
congestive heart failure as per the New York Heart Association, or acute
myocardial infarction in the past 6 months

3. Unhealed wound or ulcers persisting = 3 months

4. Psychiatric illness or a social situation that would preclude study compliance

5. Any other diseases, metabolic dysfunction, physical examination findings, or
laboratory results raising reasonable suspicion of a disease or condition that
contraindicates use of the investigational drug, that may affect interpretation
of results, or that may place the patient at high risk of treatment
complications.

- 4. Active CNS metastasis indicated by clinical symptoms, cerebral edema, steroid
requirements (not including maintenance low dose steroids), or progressive growth.

- 5. History of any secondary malignancy in the past 3 years with the exception of
curatively treated non-melanoma skin cancer or treated cervical carcinoma in situ.

- 6. Active or a history of (in the past 2 years) of autoimmune disease or syndrome
requiring systemic steroid or immunosuppressive agents.

- 7. History of interstitial lung disease.

- 8. Hepatitis B virus infection (HBsAg or anti-HBc positive, and HBV-DNA positive),
hepatitis C virus infection (anti-HCV positive, and HCV-RNA positive), or co-infection
with hepatitis B and hepatitis C (positive HBsAg or anti-HBc, and positive anti-HCV).

- 9. Human immunodeficiency virus (HIV) infection.

- 10. Major surgery, treatment with anti-cancer or investigational agents, or
radiotherapy in the 28 days prior to the first study dosing.

- 11. Treatment with immune check point inhibitors (anti-PD-1 or anti-PD-L1) in the 42
days prior to the first study dosing.

- 12. Pregnancy or breast-feeding.

- 13. Patients of reproductive age who are unable to use effective contraceptive
measures in the period from the first dose of study drug to 180 days following the
last dose of study drug. Female patients who have been amenorrheic for at least 12
months, have had a hysterectomy or oophorectomy, or have been surgically sterilized do
not require contraception.

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/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
3/05/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/02/2024
Actual
Sample size
Target
150
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Blacktown Hospital - Blacktown
Recruitment hospital [2] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [3] 0 0
Sunshine Coast University Private Hospital - Birtinya
Recruitment hospital [4] 0 0
Southern Oncology Clinical Research Unit - Adelaide
Recruitment hospital [5] 0 0
Cabrini Hospital - Brighton
Recruitment postcode(s) [1] 0 0
- Blacktown
Recruitment postcode(s) [2] 0 0
- Camperdown
Recruitment postcode(s) [3] 0 0
4575 - Birtinya
Recruitment postcode(s) [4] 0 0
- Adelaide
Recruitment postcode(s) [5] 0 0
- Brighton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Shanghai Henlius Biotech
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This Phase 1/2, multicenter, first-in-human, open-label, dose-escalation, dose expansion, and
clinical expansion study will evaluate the safety, tolerability, pharmacokinetics, and
preliminary anti-tumor efficacy of HLX301 administered as a single-agent by IV infusion every
2 weeks to patients with locally advanced or metastatic solid malignancies, who have failed
or are intolerant to standard therapy, or for whom no standard therapy is available. This
study has three parts: phase 1a dose escalation, phase 1b dose expansion, and phase 2
clinical expansion.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05102214
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/NCT05102214