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Locally Advanced or Metastatic Solid TumorsPhase 1/2NCT05102214

HLX301 (TIGIT×PDL1 Bispecific) in Patients With Locally Advanced or Metastatic Solid Tumors

A Phase 1/2 study testing HLX301 in people with Locally Advanced or Metastatic Solid Tumors and Non-small Cell Lung Cancer, run by Shanghai Henlius Biotech at 5 sites in Australia.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
HLX301
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
150 participants
Where
5 sitesAustralia
Study dates
3 May 2022to Feb 2024
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 1. Patients who meet the following criteria will be enrolled:
  • 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).
  • 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.
  • 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.
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  • 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.

Who cannot join

  • 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:
  • Ongoing or active systemic infections requiring antibiotic treatment
  • 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
  • Unhealed wound or ulcers persisting ≥ 3 months
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  • Psychiatric illness or a social situation that would preclude study compliance
  • 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.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

Australia5 sites, 5 recruiting

  • Southern Oncology Clinical Research Unit

    Adelaide, South Australia

    Ganessan Kichenadasse

    Not yet recruiting

  • Sunshine Coast University Private Hospital

    Birtinya, Queensland, 4575

    Vishwajeet Kumar, 07 5390 6057, kumarvishwa@ramsayhealth.com.au

    Michelle Morris

    Recruiting

  • Blacktown Hospital

    Blacktown, New South Wales

    Ines Silva

    Not yet recruiting

  • Cabrini Hospital

    Brighton, Victoria

    Gary Richardson

    Not yet recruiting

  • Chris O'Brien Lifehouse

    Camperdown, New South Wales

    Steven Kao

    Not yet recruiting

Other trials in Australia

About this study

Official 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

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.

Read the detailed description

Up to 150 patients will be included in this study. Up to 30 DLT evaluable patients will be enrolled in phase 1a (dose escalation), 40 per-protocol treated patients in phase 1b (dose expansion), and 80 per-protocol treated patients in phase 2.

Phase 1a uses the Bayesian optimal interval (BOIN) design, to investigate the safety and determine the MTD of HLX301. BOIN design combines rule-based and model-based design, allowing for flexibility of dose escalation and de-escalation, and high patient enrollment in doses closest to the target toxicity rate (pre-defined as 30% in this study). This study will also evaluate safety profiles at different dose levels, PK parameters, pharmacodynamic markers, immunogenicity, and the preliminary efficacy of the drug.

Following dose escalation and determination of the MTD, additional patients with NSCLC will be enrolled in phase 1b dose expansion to further evaluate PK and pharmacodynamic characteristics, and preliminary efficacy in order to determine the RP2D.

The phase 2 clinical expansion will include patients with various cancer types, including:

20 per-protocol treated patients with non-small cell lung cancer (NSCLC) 20 per-protocol treated patients with gastric/esophagogastric junction adenocarcinoma (GC/EGJ) 20 per-protocol treated patients with head and neck squamous cell carcinoma (HNSCC) 20 per-protocol treated patients with urothelial carcinoma (UC)

Being tested
HLX301
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HLX301Drug

    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

Study groups in NCT05102214
Study groupRoleWhat they receive
Phase 1a dose-escalation stageExperimentalPhase 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.
Receives: Drug: HLX301
Phase 1b dose-expansion stageExperimentalPatients 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.
Receives: Drug: HLX301
Phase 2 clinical expansion stage: Cohort AExperimental20 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.
Receives: Drug: HLX301
Phase 2 clinical expansion stage: Cohort BExperimental20 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.
Receives: Drug: HLX301
Phase 2 clinical expansion stage: Cohort CExperimental20 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.
Receives: Drug: HLX301
Phase 2 clinical expansion stage: Cohort DExperimental20 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.
Receives: Drug: HLX301

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase 1a: Safety assessments in patients receiving the trial drug

    including incidence, nature, and severity of adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

    Measured: 2 years

  2. Phase 1a: The proportion of patients experiencing dose limiting toxicity (DLT) events

    Measured: From baseline to the end of cycle 2 (28 days)

  3. Phase 1a: The maximum tolerated dose (MTD) of HLX301

    Measured: From baseline to the end of cycle 2 (28 days)

  4. Phase 1b: Recommended phase 2 dose (RP2D)

    One of the two doses in phase 1b with a more favorable safety profile, a favorable PK/PD/ADA profile, and potential clinical efficacy will be selected as the recommended phase 2 dose (RP2D)

    Measured: From baseline to 48 weeks after first infusion

  5. 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

    Objective response rate (ORR) defined as achieving a complete response or partial response as determined by the investigator according to RECIST v1.1

    • 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

    Measured: 2 years

  6. 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

    Measured: 2 years

  7. 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

    Measured: 2 years

Secondary outcomes (13)

  1. Phase 1a: The pharmacokinetic parameters of HLX301: Peak concentration (Cmax, Cmax,ss)

    Measured: 2 years

  2. Phase 1a: The pharmacokinetic parameters of HLX301: Time to peak (Tmax, Tmax,ss)

    Measured: 2 years

  3. Phase 1a: The pharmacokinetic parameters of HLX301: Area under the concentration-time curve (AUC0-inf, AUC0-t, AUCss)

    Measured: 2 years

  4. Phase 1a: The pharmacokinetic parameters of HLX301: Elimination half-life (t1/2)

    Measured: 2 years

  5. Phase 1a: The pharmacokinetic parameters of HLX301: Clearance (CL, CLss)

    Measured: 2 years

  6. Phase 1a: The pharmacokinetic parameters of HLX301: Volume of distribution (Vz, Vss)

    Measured: 2 years

  7. Phase 1a: The pharmacodynamic profiles of HLX301 as determined by receptor occupancy of HLX301 on circulating T cells

    Measured: 2 years

  8. Phase 1a: The incidence of treatment-emergent anti-drug antibodies (ADA) of HLX301

    Measured: 2 years

  9. Phase 1b: The preliminary efficacy as determined by ORR

    Measured: 2 years

  10. Phase 1b: The preliminary efficacy as determined by DCR

    Measured: 2 years

  11. Phase 1b: The preliminary efficacy as determined by DOR

    Measured: 2 years

  12. Phase 2: The safety profile

    assessing incidence, nature, and severity of adverse events according to NCI CTCAE v5.0

    Measured: 2 years

  13. 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

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Nov 2021
  2. Study start3 May 2022
  3. Primary completion15 Sep 2023 (estimated)
  4. Study completionFeb 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
150 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05102214
Sponsor's protocol ID
HLX301-001
Status last verified
Apr 2023
First submitted
29 Sep 2021
Last updated
8 Aug 2023
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Mu S, Liang Z, Wang Y, Chu W, Chen YL, Wang Q, Wang G, Wang C. PD-L1/TIGIT bispecific antibody showed survival advantage in animal model. Clin Transl Med. 2022 May;12(5):e754. doi: 10.1002/ctm2.754. No abstract available.

    PubMed 35522941

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing HLX301 in people with Locally Advanced or Metastatic Solid Tumors and Non-small Cell Lung Cancer, run by Shanghai Henlius Biotech at 5 sites in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 8 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1a: Safety assessments in patients receiving the trial drug (time frame: 2 years). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05102214, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Aug 2023.

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