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

NCT05102214 | Unknown Phase 1

• 1 other identifier: HLX301-001
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 5

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.

Conditions

Locally Advanced or Metastatic Solid Tumors; Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (7)

• 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

  2 years

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

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

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

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

• 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)

  From baseline to 48 weeks after first infusion

• 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

  2 years

• 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

  2 years

• 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

  2 years

Secondary Outcomes (13)

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

  2 years

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

  2 years

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

  2 years

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

  2 years

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

  2 years

Other Outcomes (2)

• Exploratory biomarkers: To evaluate the correlation between biomarker expression levels in baseline tumor samples using IHC staining (including, not limited to, CD8, CD4, Ki67, CD56, PD-1, TIGIT, FoxP3, CD209, PD-L1(CPS and TPS)) and tumor response

  2 years

• Exploratory biomarkers

  2 years

Study Arms (6)

Phase 1a dose-escalation stage

EXPERIMENTAL

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.

Drug: HLX301

Phase 1b dose-expansion stage

EXPERIMENTAL

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.

Drug: HLX301

Phase 2 clinical expansion stage: Cohort A

EXPERIMENTAL

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.

Drug: HLX301

Phase 2 clinical expansion stage: Cohort B

EXPERIMENTAL

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.

Drug: HLX301

Phase 2 clinical expansion stage: Cohort C

EXPERIMENTAL

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.

Drug: HLX301

Phase 2 clinical expansion stage: Cohort D

EXPERIMENTAL

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.

Drug: HLX301

Interventions

HLX301 DRUG

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

Phase 1a dose-escalation stage; Phase 1b dose-expansion stage; Phase 2 clinical expansion stage: Cohort A; Phase 2 clinical expansion stage: Cohort B; Phase 2 clinical expansion stage: Cohort C; Phase 2 clinical expansion stage: Cohort D

Eligibility Criteria

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

You may qualify if:

• \. 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.
• \. Age ≥ 18 years, or legally an adult as per local regulations.
• \. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• \. Measurable disease according to RECIST Version 1.1
• \. Able to provide informed consent.
• \. A life expectancy longer than three months.
• \. 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.
• \. 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.
• \. Adequate renal function, defined as serum creatinine ≤ 1.5x upper limit of normal (ULN).
• \. 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.

You may not qualify if:

• \. Received prior anti-TIGIT therapy.
• \. Patients who still have persistent ≥ grade 2 toxicities from prior therapies.
• \. 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
• 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.
• \. Active CNS metastasis indicated by clinical symptoms, cerebral edema, steroid requirements (not including maintenance low dose steroids), or progressive growth.
• \. 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.
• \. Active or a history of (in the past 2 years) of autoimmune disease or syndrome requiring systemic steroid or immunosuppressive agents.
• \. History of interstitial lung disease.
• \. 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).
• \. Human immunodeficiency virus (HIV) infection.
• \. Major surgery, treatment with anti-cancer or investigational agents, or radiotherapy in the 28 days prior to the first study dosing.

Sponsors & Collaborators

• Shanghai Henlius Biotech: lead

Study Sites (5)

Blacktown Hospital

Blacktown, New South Wales, Australia

NOT YET RECRUITING

Chris O'Brien Lifehouse

Camperdown, New South Wales, Australia

NOT YET RECRUITING

Sunshine Coast University Private Hospital

Birtinya, Queensland, 4575, Australia

RECRUITING

Southern Oncology Clinical Research Unit

Adelaide, South Australia, Australia

NOT YET RECRUITING

Cabrini Hospital

Brighton, Victoria, Australia

NOT YET RECRUITING

Related Publications (1)

• 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.

  PMID: 35522941 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

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

Study Record Dates

• First Submitted: September 29, 2021
• First Posted: November 1, 2021
• Study Start: May 3, 2022
• Primary Completion: September 15, 2023
• Study Completion: February 1, 2024
• Last Updated: August 8, 2023

Record last verified: 2023-04

Locations

AU (5)