Clinical trial NCT05940116: A Phase I Clinical Study of HS-20117 in Participants With Advanced Solid Tumors
Official title: A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of HS-20117 in Participants With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Non-Small Cell Lung Cancer
Solid Tumor
Keywords: Non-Small Cell Lung Cancer
Solid Tumor
HS-20117
Epidermal Growth Factor Receptor
c-Mesenchymal-Epithelial Transition
Bispecific Antibody
EGFR exon 20 insertion
Lead sponsor: Hansoh BioMedical R&D Company
Sponsor class: INDUSTRY
First posted: 2023-07-11
Enrollment: 322
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: HS-20117 is a fully-human EGFR-MET immunoglobulin G1(IgG1)-like bispecific antibody. The purpose of study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of HS-20117 as a monotherapy for participants with advanced solid tumors.

Detailed description: This is a multicenter, open-label, Phase I clinical study of HS-20117 to evaluate the safety, tolerability, PK, immunogenicity and efficacy in participants with advanced solid tumors. The study consists of phase Ia (dose escalation) and phase Ib (dose expansion). The dose-escalation study will be performed to evaluate the safety, tolerability, PK profile, immunogenicity, and efficacy of HS-20117 in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. The subsequent dose-expansion study will be performed to evaluate the efficacy of HS-20117 in participants with locally advanced or metastatic NSCLC who have progressed after prior platinum-based chemotherapy or are intolerant to platinum-based chemotherapy with EGFR exon 20 insertion mutations, and to explore the efficacy of HS-20117 in participants with other advanced solid tumors.

Eligibility criteria: Inclusion Criteria:

1. Males or females aged 18 - 75 years (inclusive).
2. For the phase Ia study: Participants with locally advanced or metastatic NSCLC (stage IIIB/IIIC/IV) with EGFR-activating mutations who have progressed after or are intolerant to or not available to standard of care (SoC).
3. For the phase Ib study:

   Cohort A: Participants with locally advanced or metastatic NSCLC (stage IIIB/IIIC/IV) with EGFR exon 20ins mutations who have progressed after prior platinum-based chemotherapy or are intolerant to platinum-based chemotherapy.

   Cohort B: Participants with other advanced solid tumors who have progressed after prior SoC or are intolerant to SoC.
4. Agree to provide fresh or archival tumor tissue.
5. At least one target lesion per the RECIST v1.1.
6. ECOG performance status of 0-1.
7. Minimum life expectancy \> 12 weeks.
8. Males or Females should be using adequate contraceptive measures throughout the study.
9. Females must not be pregnant at screening or have evidence of non-childbearing potential.
10. Have signed Informed Consent Form.

Exclusion Criteria:

1. Received or are receiving the following treatments:

   1. For the phase Ib study Cohort A: Previous or current treatment with EGFR exon 20ins targeted therapy.
   2. Traditional Chinese medicine indicated for tumors within 2 weeks prior to the first dose of HS-20117.
   3. Cytotoxic chemotherapies, investigational drugs or other systematic anti-tumor therapies within 3 weeks prior to the first dose of HS-20117.
   4. Antibodies within 4 weeks prior to the first dose of HS-20117.
   5. Local radiotherapy within 2 weeks prior to the first dose of HS-20117, more than 30% of bone marrow irradiation or large-area radiotherapy within 4 weeks before the first dose of HS-20117.
   6. Presence of pleural effusion/ascites requiring clinical intervention; presence of pericardial effusion.
   7. Major surgery within 4 weeks prior to the first dose of HS-20117.
2. Presence of Grade ≥ 2 toxicities due to prior anti-tumor therapy.
3. History of other primary malignancies.
4. Untreated, or active central nervous system metastases.
5. Inadequate bone marrow reserve or organ functions.
6. Severe, uncontrolled or active cardiovascular disorders.
7. Severe or uncontrolled systemic diseases.
8. Severe bleeding symptoms or bleeding tendencies within 1 month prior to the first dose of HS-20117.
9. Severe arteriovenous thrombosis occurred within 3 months prior to the first dose of HS-20117
10. Serious infection within 4 weeks prior to the first dose of HS-20117.
11. Active infectious diseases.
12. Interstitial lung disease (ILD).
13. Serious neurological or mental disorders.
14. History of hypersensitivity to any component of HS-20117 or similar drugs.
15. Participants with any condition that compromises the safety of the participant or interferes with the assessment of the study, as judged by the investigator.

Primary outcomes:
measure: [Phase 1a] Maximum tolerated dose (MTD) of HS-20117
timeFrame: Cycle 1 (28 days)
measure: [Phase 1a] Maximum applicable dose (MAD) of HS-20117
timeFrame: Cycle 1 (28 days)
measure: [Phase 1b] Efficacy of HS-20117: Objective response rate (ORR)
timeFrame: From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years
Secondary outcomes:
measure: [phase 1a and 1b] Incidence and severity of treatment-emergent adverse events
timeFrame: From the date of first dose until 90 days after the final dose. A cycle is 28 days
measure: [phase 1a and 1b] PK parameters: Maximum serum concentration (Cmax) of HS-20117
timeFrame: From the date of first dose until 30 days after the final dose. A cycle is 28 days.
measure: [phase 1a and 1b] PK parameters: Trough serum concentration (Ctrough) of HS-20117
timeFrame: From the date of first dose until 30 days after the final dose. A cycle is 28 days.
measure: [phase 1a and 1b] PK parameters: Time to reach maximum observed serum concentration (Tmax) of HS-20117
timeFrame: From the date of first dose until 30 days after the final dose. A cycle is 28 days
measure: [phase 1a] PK parameters: Area under the curve from time Zero to end of dosing interval (AUCtau) of HS-20117
timeFrame: From the date of first dose until 30 days after the final dose. A cycle is 28 days.
measure: [phase 1a] PK parameters: Terminal elimination half-life (t1/2) of HS-20117
timeFrame: From the date of first dose until 30 days after the final dose. A cycle is 28 days.
measure: [phase 1a] Efficacy of HS-20117: ORR
timeFrame: From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years.
measure: [phase 1a and 1b] Efficacy of HS-20117: disease control rate (DCR)
timeFrame: From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years.
measure: [phase 1a and 1b] Efficacy of HS-20117: duration of response (DoR)
timeFrame: From the date of CR, PR until the date of disease progression or death, approximately 2 years.
measure: [phase 1a and 1b] Efficacy of HS-20117: progression free survival (PFS)
timeFrame: From the date of randomization or first dose (if randomization is not needed) until the date of disease progression or death, approximately 2 years.
measure: [phase 1b] Efficacy of HS-20117: overall survival (OS)
timeFrame: From the date of randomization or first dose (if randomization is not needed) until the documentation of death from any cause, approximately 4 years
measure: [phase 1a and 1b] Immunogenicity of HS-20117
timeFrame: Cycle 1 Day 1: predose through EOT or follow up period (90 days after the last dose).
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
Study officials:
affiliation: Tianjin Medical University Cancer Institute and Hospital
name: Dingzhi Huang
role: PRINCIPAL_INVESTIGATOR
References: