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

Overview

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.

Interventions

• Drug HS-20117
  Phase Ia: patients will receive HS-20117 starting at 400 mg, and subsequent cohorts will test escalating doses, if tolerated, until a maximum tolerated dose (MTD) or maximum applicable dose (MAD) is defined. Phase Ib: patients will receive HS-20117 at MED or MAD

Primary outcome measures

• [Phase 1a] Maximum tolerated dose (MTD) of HS-20117 [Time frame: Cycle 1 (28 days)]
• [Phase 1a] Maximum applicable dose (MAD) of HS-20117 [Time frame: Cycle 1 (28 days)]
• [Phase 1b] Efficacy of HS-20117: Objective response rate (ORR) [Time frame: From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years]

Secondary outcome measures (12)

• [phase 1a and 1b] Incidence and severity of treatment-emergent adverse events [Time frame: From the date of first dose until 90 days after the final dose. A cycle is 28 days]
• [phase 1a and 1b] PK parameters: Maximum serum concentration (Cmax) of HS-20117 [Time frame: From the date of first dose until 30 days after the final dose. A cycle is 28 days.]
• [phase 1a and 1b] PK parameters: Trough serum concentration (Ctrough) of HS-20117 [Time frame: From the date of first dose until 30 days after the final dose. A cycle is 28 days.]
• [phase 1a and 1b] PK parameters: Time to reach maximum observed serum concentration (Tmax) of HS-20117 [Time frame: From the date of first dose until 30 days after the final dose. A cycle is 28 days]
• [phase 1a] PK parameters: Area under the curve from time Zero to end of dosing interval (AUCtau) of HS-20117 [Time frame: From the date of first dose until 30 days after the final dose. A cycle is 28 days.]
• [phase 1a] PK parameters: Terminal elimination half-life (t1/2) of HS-20117 [Time frame: From the date of first dose until 30 days after the final dose. A cycle is 28 days.]
• [phase 1a] Efficacy of HS-20117: ORR [Time frame: From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years.]
• [phase 1a and 1b] Efficacy of HS-20117: disease control rate (DCR) [Time frame: From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years.]
• [phase 1a and 1b] Efficacy of HS-20117: duration of response (DoR) [Time frame: From the date of CR, PR until the date of disease progression or death, approximately 2 years.]
• [phase 1a and 1b] Efficacy of HS-20117: progression free survival (PFS) [Time frame: From the date of randomization or first dose (if randomization is not needed) until the date of disease progression or death, approximately 2 years.]
• [phase 1b] Efficacy of HS-20117: overall survival (OS) [Time frame: From the date of randomization or first dose (if randomization is not needed) until the documentation of death from any cause, approximately 4 years]
• [phase 1a and 1b] Immunogenicity of HS-20117 [Time frame: Cycle 1 Day 1: predose through EOT or follow up period (90 days after the last dose).]

Eligibility criteria

Inclusion criteria

• Males or females aged 18 - 75 years (inclusive).
• 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).
• 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.

• Agree to provide fresh or archival tumor tissue.
• At least one target lesion per the RECIST v1.1.
• ECOG performance status of 0-1.
• Minimum life expectancy > 12 weeks.
• Males or Females should be using adequate contraceptive measures throughout the study.
• Females must not be pregnant at screening or have evidence of non-childbearing potential.
• Have signed Informed Consent Form.

Exclusion criteria

• Received or are receiving the following treatments:

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Tianjin Medical University Cancer Institute and Hospital — Tianjin

Identifiers

NCT: NCT05940116 · HS-20117-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗