## Protocol Section
### Identification Module
**NCT ID:** NCT06417008

**Brief Title:** A Study of HS-20117 Combined With Aumolertinib in Participants With Advanced Non-Squamous Non-Small Cell Lung Cancer

**Official Title:** A Phase Ib/III Clinical Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Immunogenicity of HS-20117 Combined With Aumolertinib in Participants With Advanced Non-Squamous Non-Small Cell Lung Cancer

#### Organization Study ID Info
**ID:** HS-20117-301
#### Organization
**Class:** INDUSTRY
**Full Name:** Hansoh BioMedical R&D Company
### Status Module
#### Completion Date
**Date:** 2030-06-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-20

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-16

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-06-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-16
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-12
**Study First Submit QC Date:** 2024-05-12
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Hansoh BioMedical R&D Company

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** HS-20117 is a fully-human EGFR-MET immunoglobulin G1(IgG1)-like bispecific antibody. The purpose of this study is to assess the safety, efficacy, pharmacokinetics and immunogenicity of HS-20117 combined with Aumolertinib in participants with epidermal growth factor receptor (EGFR) mutation (Exon 19 deletions \[Exon 19del\] or Exon 21 L858R substitution) positive, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC).

**Detailed Description:** This is a multicenter Phase Ib/III clinical study evaluating the safety, efficacy, pharmacokinetics (PK), and immunogenicity of HS-20117 in combination with aumolertinib in subjects with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC). The study is divided into two phases, Phase Ib, a dose expansion study and Phase III, a confirmatory study. In the dose expansion phase (Phase Ib), HS-20117 will first be studied in combination with the standard dose of aumolertinib, to assess the efficacy, safety, tolerability, PK profile, and immunogenicity of HS-20117 in combination with aumolertinib in the target population, as well as to determine the recommended Phase III dose (RP3D). Following confirmation of the safety and efficacy of HS-20117 in combination with aumolertinib and RP3D in Phase Ib, a randomized, active-controlled, open-label, multicenter Phase III study will be initiated to assess the efficacy and safety of HS-20117 in combination with aumolertinib versus aumolertinib in the target population in the confirmatory study phase.

### Conditions Module

**Conditions:**

- Non-Squamous Non-Small Cell Lung Cancer

**Keywords:**

- Non-Small Cell Lung Cancer

- HS-20117

- Epidermal Growth Factor Receptor

- c-Mesenchymal-Epithelial Transition

- Bispecific Antibody

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 1080

**Type:** ESTIMATED

**Phases:**

- PHASE2

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Participants will receive IV infusion of HS-20117 once during cycle 1 and once every 2 weeks during subsequent cycles (The duration of each treatment cycle is 28 days) at exploratory doses. Aumolertinib will be administered 110 mg orally once daily.

**Intervention Names:**

- Drug: HS-20117

- Drug: Aumolertinib

**Label:** Phase Ib: HS-20117 and Aumolertinib

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Participants will receive IV infusion of HS-20117 once during cycle 1 and once every 2 weeks during subsequent cycles (The duration of each treatment cycle is 28 days) at exploratory doses. Aumolertinib will be administered 110 mg orally once daily.

**Intervention Names:**

- Drug: HS-20117

- Drug: Aumolertinib

**Label:** Phase III: HS-20117 and Aumolertinib

**Type:** EXPERIMENTAL

#### Arm Group 3

**Description:** Participants will receive Aumolertinib 110 mg orally once daily.

**Intervention Names:**

- Drug: Aumolertinib

**Label:** Phase III: Aumolertinib

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Phase III: HS-20117 and Aumolertinib

- Phase Ib: HS-20117 and Aumolertinib

**Description:** Participants will receive HS-20117 once during cycle 1 and once every 2 weeks during subsequent cycles (The duration of each treatment cycle is 28 days)

**Name:** HS-20117

**Other Names:**

- PM1080

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Phase III: Aumolertinib

- Phase III: HS-20117 and Aumolertinib

- Phase Ib: HS-20117 and Aumolertinib

**Description:** 110 mg orally once daily.

**Name:** Aumolertinib

**Other Names:**

- Almonertinib Mesilate Tablets

- HS-10296

- Almonertinib

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** ORR is defined as the percentage of participants with DOR of confirmed CR or confirmed PR per RECIST v1.1

**Measure:** [Phase Ib] Objective response rate (ORR) According to response evaluation criteria in solid tumors (RECIST) v1.1 by Investigators (INVs)

**Time Frame:** From the date of first dose until the date of disease progression or withdrawal from study, up to approximately 40 months

**Description:** PFS is defined as the time from randomization until the date of objective disease progression or death, whichever occurred first, based on IRC using RECIST v1.1

**Measure:** [Phase III] Progression-Free Survival (PFS) According to RECIST v1.1 by Independent Review Committee(IRC)

**Time Frame:** Up to approximately 40 months

#### Secondary Outcomes

**Description:** Overall Survival is defined as the time from the date of randomization to the date of participant's death due to any cause.

**Measure:** [Phase Ib and III] Overall Survival (OS)

**Time Frame:** Approximately 60 months

**Description:** DCR is deﬁned as the percentage of patients who have a best overall response (confirmed CR, PR, or stable disease for at least 6 weeks) based on Investigator's assessment per RECIST v1.1.

**Measure:** [Phase Ib and III] Disease control rate (DCR) According to RECIST v1.1 by INVs

**Time Frame:** From the date of first dose until the date of disease progression or withdrawal from study, approximately 40 months.

**Description:** DoR only applies to participants whose best overall response is CR or PR based on Investigator's assessment per RECIST v1.1. The start date is the date of first documented response of CR or PR (i.e. the start date of observed response, not the date when response was confirmed), and the end date is defined as the date of the first documented progression or death due to underlying disease.

**Measure:** [Phase Ib and III] Duration of response (DoR) According to RECIST v1.1 by INVs

**Time Frame:** From the date of CR, PR until the date of disease progression or death, approximately 40 months.

**Description:** PFS is defined as the time from randomization until the date of objective disease progression or death, whichever occurred first, based on IRC using RECIST v1.1

**Measure:** [Phase Ib and III] Progression-Free Survival (PFS) According to RECIST v1.1 by INVs

**Time Frame:** Up to approximately 40 months

**Description:** ORR is defined as the percentage of participants with BOR of confirmed CR or confirmed PR per RECIST v1.1

**Measure:** [Phase III] ORR According to RECIST v1.1 by INVs

**Time Frame:** From the date of first dose until the date of disease progression or withdrawal from study, up to approximately 40 months

**Description:** ORR is defined as the percentage of participants with BOR of confirmed CR or confirmed PR per RECIST v1.1

**Measure:** [Phase III] ORR According to RECIST v1.1 by IRC

**Time Frame:** From the date of first dose until the date of disease progression or withdrawal from study, up to approximately 40 months

**Description:** DCR is deﬁned as the percentage of patients who have a best overall response (confirmed CR, PR, or stable disease for at least 6 weeks)

**Measure:** [Phase III] DCR According to RECIST v1.1 by IRC

**Time Frame:** From the date of first dose until the date of disease progression or withdrawal from study, approximately 40 months.

**Description:** DoR only applies to participants whose best overall response is CR or PR. The start date is the date of first documented response of CR or PR (i.e. the start date of observed response, not the date when response was confirmed), and the end date is defined as the date of the first documented progression or death due to underlying disease.

**Measure:** [Phase III] DoR According to RECIST v1.1 by IRC

**Time Frame:** From the date of CR, PR until the date of disease progression or death, approximately 40 months.

**Description:** Adverse event (assessed according to NCI CTCAE v5.0) is defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.

**Measure:** [Phase Ib and III] 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.

**Description:** Immunogenicity will be measured by the number of participants that are ADA positive.

**Measure:** [Phase Ib and III] Immunogenicity of HS-20117

**Time Frame:** Cycle 1 Day 1: predose through EOT or follow up period (90 days after the last dose).

**Description:** The Cmax is the maximum observed serum concentration of HS-20117

**Measure:** [Phase Ib] 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.

**Description:** Ctrough is the observed serum concentration immediately prior to the next administration

**Measure:** [Phase Ib] 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.

**Description:** The AUCtau is defined as the area under the serum concentration-time curve during a dose interval time period(tau)

**Measure:** [Phase Ib] 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

**Description:** The Tmax is defined as time to reach maximum observed serum concentration of HS-20117

**Measure:** [Phase Ib] 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.

**Description:** The t1/2 is defined as the time it takes for the concentration levels to fall to 50% of their value.

**Measure:** [Phase Ib] 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.

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Males or females aged 18 - 75 years (inclusive).
* Participants with newly diagnosed histologically or cytologically confirmed, locally advanced or metastatic EGFR-sensitive mutated NSCLC (stage IIIB/IIIC/IV) that is treatment naive and not amenable to curative therapy including surgical resection or chemoradiation.
* 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:

  1. Previous or current treatment with MET targeted therapy or EGFR targeted antibodies or antibody-drug conjugates (ADC).
  2. Traditional Chinese medicine indicated for tumors within 2 weeks prior to the first dose of study drug.
  3. Local radiotherapy within 2 weeks prior to the first dose of study drug, more than 30% of bone marrow irradiation or large-area radiotherapy within 4 weeks before the first dose of study drug.
  4. Presence of pleural effusion/ascites requiring clinical intervention; presence of pericardial effusion.
  5. Major surgery within 4 weeks prior to the first dose of study drug.
* 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 study drug.
* Severe arteriovenous thrombosis occurred within 3 months prior to the first dose of study drug.
* Serious infection within 4 weeks prior to the first dose of study drug.
* Active infectious diseases.
* Interstitial lung disease (ILD).
* Serious neurological or mental disorders.
* History of hypersensitivity to any component of HS-20117 and Aumolertinib or their 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.

**Maximum Age:** 75 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** fujl@hspharm.com

**Name:** Jialei Fu

**Phone:** +86 18652105685

**Role:** CONTACT

#### Overall Officials

**Official 1:**

**Affiliation:** Tianjin Medical University Cancer Institute and Hospital

**Name:** Dingzhi Huang, M.D.

**Role:** PRINCIPAL_INVESTIGATOR

**Official 2:**

**Affiliation:** Zhejiang Cancer Hspital

**Name:** Yun Fan, M.D.

**Role:** PRINCIPAL_INVESTIGATOR

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000012142

- Term: Respiratory Tract Neoplasms

- ID: D000013899

- Term: Thoracic Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000009369

- Term: Neoplasms

- ID: D000008171

- Term: Lung Diseases

- ID: D000012140

- Term: Respiratory Tract Diseases

- ID: D000002283

- Term: Carcinoma, Bronchogenic

- ID: D000001984

- Term: Bronchial Neoplasms

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC08

- Name: Respiratory Tract (Lung and Bronchial) Diseases

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M5546

- Name: Carcinoma, Non-Small-Cell Lung

- Relevance: HIGH

- As Found: Non-Small Cell Lung Cancer

- ID: M11172

- Name: Lung Neoplasms

- Relevance: HIGH

- As Found: Lung Cancer

- ID: M5534

- Name: Carcinoma

- Relevance: LOW

- As Found: Unknown

- ID: M14979

- Name: Respiratory Tract Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M16658

- Name: Thoracic Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M11168

- Name: Lung Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14977

- Name: Respiratory Tract Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5540

- Name: Carcinoma, Bronchogenic

- Relevance: LOW

- As Found: Unknown

- ID: M5260

- Name: Bronchial Neoplasms

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000008175

- Term: Lung Neoplasms

- ID: D000002289

- Term: Carcinoma, Non-Small-Cell Lung

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M4225

- Name: Antibodies

- Relevance: LOW

- As Found: Unknown

- ID: M20194

- Name: Antibodies, Bispecific

- Relevance: LOW

- As Found: Unknown

- ID: M10184

- Name: Immunoglobulins

- Relevance: LOW

- As Found: Unknown

- ID: M11900

- Name: Mitogens

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
