## Protocol Section
### Identification Module
**NCT ID:** NCT05263479

**Brief Title:** A Study of HS-20089 in Patients With Advanced Solid Tumors

**Official Title:** A Phase I, Open-label, Multicenter Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of HS-20089 in Patients With Advanced Solid Tumors

#### Organization Study ID Info
**ID:** HS-20089-101
#### Organization
**Class:** INDUSTRY
**Full Name:** Hansoh BioMedical R&D Company
### Status Module
#### Completion Date
**Date:** 2026-12-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-04-03

**Type:** ACTUAL

**Last Update Submit Date:** 2024-04-01

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2024-12-31

**Type:** ESTIMATED

#### Start Date
**Date:** 2022-01-05

**Type:** ACTUAL

**Status Verified Date:** 2024-04

#### Study First Post Date
**Date:** 2022-03-02
**Type:** ACTUAL
**Study First Submit Date:** 2021-10-29
**Study First Submit QC Date:** 2022-02-21
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Shanghai Hansoh Biomedical Co., Ltd

#### 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-20089 is a novel DAR-6 antibody-drug conjugate （ADC） targeting B7-H4. In preclinical studies, it inhibited tumor cell growth expressing B7-H4 in vitro and in vivo. The first-in-human trial is conducted to assess the maximum tolerated dose (MTD) and dose limiting toxicity (DLT), to evaluate the pharmacokinetics, safety and preliminary anti-tumor activity of HS-20089 in Patients With Advanced Solid Tumors.

**Detailed Description:** This is a Phase 1a/1b open-label, multicenter study with dose escalation and dose expansion cohorts to evaluate the safety, tolerability, PK and preliminary efficacy of HS-20089 in patients with advanced solid tumors.

The Dose Escalation will include an initial accelerated titration design followed by a Bayesian optimal interval (BOIN) design. Enrollment into Dose Expansion will begin after identification of the MTD and/or MAD in Phase 1a. In Phase 1b, preliminary efficacy will be evaluated in planned expansion cohorts that include patients with specific tumor types that are B7-H4+ advanced solid tumors.

### Conditions Module

**Conditions:**

- Advanced Solid Tumor

**Keywords:**

- HS-20089

- ADC

- B7-H4

- Advanced Solid Tumor

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** SEQUENTIAL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 177

**Type:** ESTIMATED

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** HS-20089 for IV infusion of various dose strengths administered in 21 day dosing cycles.

**Intervention Names:**

- Drug: HS-20089 (Phase Ia：Dose escalation )

**Label:** HS-20089 (Phase Ia：Dose escalation )

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** The recommended dose from the dose-escalation stage and other potential doses will be further explored.

**Intervention Names:**

- Drug: HS-20089 (Phase Ib: Dose expansion)

**Label:** HS-20089 (Phase Ib: Dose expansion)

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- HS-20089 (Phase Ia：Dose escalation )

**Description:** Participants will receive HS-20089 in 21 day dosing cycles. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.

**Name:** HS-20089 (Phase Ia：Dose escalation )

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- HS-20089 (Phase Ib: Dose expansion)

**Description:** IV administration of HS-20089 Q3W; Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and confirmed disease progression.

**Name:** HS-20089 (Phase Ib: Dose expansion)

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** To determine the MTD for further evaluation of IV administration of HS-20089 in subjects with advanced solid tumors.

**Measure:** Maximum Tolerated Dose of HS-20089

**Time Frame:** 3 weeks after initiation of treatment

#### Secondary Outcomes

**Description:** The CTCAE criteria will be used to assess adverse events on this trial.

**Measure:** Incidence and severity of treatment-emergent adverse events

**Time Frame:** Baseline through study completion(90 days after last dose)

**Description:** Cmax will be obtained after single dose of HS-20089 on Day 1.

**Measure:** Observed maximum plasma concentration (Cmax) after single dose of HS-20089

**Time Frame:** From pre-dose to 120 hours after single dose on Day 1

**Description:** Cmax ss will be obtained on Day 1 of dosing in the 21-Day cycle of therapy.

**Measure:** Observed maximum plasma concentration (Cmax ss) after multiple dose of HS-20089

**Time Frame:** From pre-dose to 24 hours after the dose on Day 1 of the 21-Day cycle of therapy

**Description:** Apparent terminal half-life is the time measured for the concentration to decrease by one half.

**Measure:** Apparent terminal half-life (t1/2) after single dose of HS-20089

**Time Frame:** From pre-dose to 120 hours after single dose on Day 1

**Description:** Area under the plasma concentration versus time curve from time zero to the 24-hour sampling time at which the concentration was at or above the lower limit of quantification (LLQ).

**Measure:** Area under plasma concentration versus time curve from zero to the 24-hour sampling time (AUC0-24) after single dose of HS-20089

**Time Frame:** From pre-dose to 24 hours after single dose on Day 1

**Description:** Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ).

**Measure:** Area under plasma concentration versus time curve from zero to last sampling time (AUC0-t) after single dose of HS-20089

**Time Frame:** From pre-dose to 120 hours after single dose on Day 1

**Description:** AUC0-∞ was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast/ λz, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the LLQ and λz is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.

**Measure:** Area under the plasma concentration versus time curve from time zero to infinity (AUC0-∞) after single dose of HS-20089

**Time Frame:** From pre-dose to 120 hours after single dose on Day 1

**Description:** Anti-tumor efficacy will be assessed by best radiographic response based on Response Evaluation Criteria in Solid Tumors at baseline (Day -28 to -1). For patients that continue on repeating 21-Day cycles after the primary evaluation period, progression will be assessed after each 6 weeks of therapy. ORR is defined as the percentage of patients with a complete response (CR) or partial response (PR) that was confirmed at a subsequent scan at least 4 weeks later, as assessed according to RECIST version 1.1.

**Measure:** To further evaluation of the anti-tumor activity of HS-20089 by assessment of objective response rate (ORR)

**Time Frame:** From the date of first occurrence of complete response (CR) or partial response (PR) on 2 consecutive occasions (≥4 weeks), until the date of disease progression or withdrawal from study，up to 2 years

**Description:** Number of participants who test positive for ADA to HS-20089 will be reported.

**Measure:** Anti-drug Antibodies (ADA) of HS-20089

**Time Frame:** Baseline through study completion(90 days after last dose)

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Men or women aged more than or equal to (≥) 18 years
2. Advanced solid tumor patients confirmed by histology or cytology for who that standard treatment is invalid, unavailable or intolerable
3. Patients have at least one target lesion according to RECEST 1.1. The requirements for target lesions are: measurable lesions without local treatment such as irradiation, or with definite progress after local treatment, with the longest diameter ≥ 10 mm in the baseline period (in case of lymph nodes, the shortest axis ≥ 15 mm is required)
4. ECOG performance status was 0-1 and did not deteriorate in the previous 2 weeks
5. Estimated life expectancy greater than (\>) 12 weeks
6. Females should be using adequate contraceptive measures throughout the study; should not be breastfeeding at the time of screening, during the study and until 3 months after completion of the study; and must have evidence of non-childbearing potential
7. Sign Informed Consent Form

Exclusion Criteria:

1. Treatment with any of the following:

   1. Previous or current treatment with drugs targeting B7-H4
   2. Any cytotoxic chemotherapy, investigational agents or anticancer drugs within 28 days of the first dose of study drug
   3. Radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study drug, or patients received more than 30% of the bone marrow irradiation, or large-scale radiotherapy within 4 weeks of the first dose.
   4. Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks of the first dose of study drug.
   5. Known and untreated, or active central nervous system metastases.
2. Existing abnormal CTCAE≥grade 2 resulted from previous treatment
3. History of other malignancy
4. Inadequate bone marrow reserve or organ function
5. Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV), unless the hepatitis is considered to be cured, Known history of HIV
6. History of hypersensitivity to any active or inactive ingredient of HS-20089.
7. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.
8. Any disease or condition that, in the opinion of the investigator, would compromise the safety of the patient or interfere with study assessments.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** wujiong1122@vip.sina.com

**Name:** Jiong Wu, PhD

**Phone:** 13601637369

**Role:** CONTACT

**Contact 2:**

**Email:** Syner2000@163.com

**Name:** Jian Zhang, PhD

**Phone:** 18017312991

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Shanghai

**Contacts:**

***Contact 1:***

- **Email:** wujiong1122@vip.sina.com

- **Name:** Jiong Wu, PhD

- **Phone:** 13601637369

- **Role:** CONTACT

***Contact 2:***

- **Email:** Syner2000@163.com

- **Name:** Jian Zhang, PhD

- **Phone:** 18017312991

- **Role:** CONTACT

**Country:** China

**Facility:** Fudan University Cancer Hospital

**State:** Shanghai

**Status:** RECRUITING

**Zip:** 200032

#### Overall Officials

**Official 1:**

**Affiliation:** Fudan University

**Name:** Jiong Wu, PhD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Meshes

- ID: D000009369

- Term: Neoplasms

### Misc Info Module

- Version Holder: 2024-05-24
