## Protocol Section
### Identification Module
**NCT ID:** NCT06419621

**Brief Title:** PM8002 or Placebo Plus Nab-Paclitaxel as First-line Treatment in Inoperable Locally Advanced/Metastatic Triple-negative Breast Cancer

**Official Title:** A Multicenter, Randomized, Double-blind Phase III Study of PM8002 or Placebo in Combination With Nab-Paclitaxel as First-line Treatment in Inoperable Locally Advanced/Metastatic Triple-negative Breast Cancer(TNBC)

#### Organization Study ID Info
**ID:** PM8002-C013C-TNBC-R
#### Organization
**Class:** INDUSTRY
**Full Name:** Biotheus Inc.
### Status Module
#### Completion Date
**Date:** 2028-07

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-28

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-24

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2027-07

**Type:** ESTIMATED

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

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-17
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-14
**Study First Submit QC Date:** 2024-05-14
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Biotheus Inc.

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Is US Export:** False

### Description Module

**Brief Summary:** This multicenter, randomized, double-blind study will evaluate the safety and efficacy of PM8002 in combination with Nab-Paclitaxel compared with placebo combined with Nab-Paclitaxel as first-line treatment in inoperable locally advanced/metastatic triple-negative breast cancer(TNBC)

### Conditions Module

**Conditions:**

- Triple Negative Breast Cancer(TNBC)

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** QUADRUPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 360

**Type:** ESTIMATED

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Patients will receive both PM8002 and Nab-Paclitaxel.

**Intervention Names:**

- Drug: PM8002

- Drug: Nab-Paclitaxel

**Label:** PM8002 Plus Nab-Paclitaxel

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Patients will receive both Placebo and Nab-Paclitaxel.

**Intervention Names:**

- Drug: Nab-Paclitaxel

- Drug: Placebo

**Label:** Placebo Plus Nab-Paclitaxel

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- PM8002 Plus Nab-Paclitaxel

**Description:** PM8002 20 mg/kg via intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle

**Name:** PM8002

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- PM8002 Plus Nab-Paclitaxel

- Placebo Plus Nab-Paclitaxel

**Description:** Nab-Paclitaxel 100mg/m2 via IV infusion on Days 1, 8, and 15 of each 28-day cycle

**Name:** Nab-Paclitaxel

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- Placebo Plus Nab-Paclitaxel

**Description:** Placebo 20 mg/kg via IV infusion on Days 1 and 15 of each 28-day cycle

**Name:** Placebo

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Progression-free survival is defined as the time from randomization to the first documented progressive disease (PD) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) based on assessments by Blinded Independent Review Committee (BIRC) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD.

**Measure:** Progression-Free Survival (PFS) assessed by Blinded Independent Review Committee (BIRC)

**Time Frame:** Up to approximately 37 months from first patient in

**Description:** Overall survival is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis are censored at the date of the last follow-up.

**Measure:** Overall Survival (OS)

**Time Frame:** Up to approximately 37 months from first patient in

#### Secondary Outcomes

**Description:** Progression-free survival is defined as the time from randomization to the first documented PD per RECIST 1.1 based on assessments by investigator or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD.

**Measure:** PFS assessed by investigator

**Time Frame:** Up to approximately 37 months from first patient in

**Description:** ORR is defined as the percentage of participants in the analysis population who have a complete response (CR: disappearance of all lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experienced a CR or PR as assessed by BIRC or investigators based on RECIST 1.1 is presented.

**Measure:** Objective response rate (ORR) assessed by BIRC or investigators

**Time Frame:** Up to approximately 37 months from first patient in

**Description:** DCR is defined as the sum rate of CR, PR and Stable Disease (SD), as determined by BIRC or investigators using RECIST v1.1

**Measure:** Disease control rate (DCR) assessed by BIRC or investigators

**Time Frame:** Up to approximately 37 months from first patient in

**Description:** DoR is defined as the time period from the date of initial CR or PR until the date of PD or death due to any cause, whichever occurs first.

**Measure:** Duration of response (DoR) assessed by BIRC or investigators

**Time Frame:** Up to approximately 37 months from first patient in

**Description:** An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.

**Measure:** Incidence and severity of Adverse Event (AE) according to CTCAE 5.0

**Time Frame:** Up to 30 days after last treatment

**Description:** The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" (Item 29) and "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score are presented.

**Measure:** Differences in the scores of health-related quality of life (HRQol) evaluated by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30)

**Time Frame:** Up to 30 days after last treatment

**Description:** Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score denotes worse symptoms for the systemic therapy side effects symptom scale.

**Measure:** Differences in the scores of health-related quality of life (HRQol) evaluated by EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR42)

**Time Frame:** Up to 30 days after last treatment

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Ability to understand and willing to provide written informed consent and to comply with scheduled visits and study procedures;
* Female, aged 18 to 70 years (inclusive);
* Histologically confirmed unresectable locally advanced or metastatic breast cancer with negative status for ER, PR, and HER-2. Testing results for all three markers conducted within 24 months prior to the initiation of the study by a local facility accredited by clinical research center are acceptable. If deemed necessary by the investigator during screening, subjects may provide additional biopsy to confirm the latest pathological;
* Subjects who have not received prior systemic treatment（except endocrine therapy） for advanced breast cancer are eligible for the study. Subjects who have received Taxane-based chemotherapy during the neoadjuvant and/or adjuvant treatment phase are eligible, as long as the occurrence of relapse or metastasis is at least 12 months after the end of treatment;
* Performance status as assessed by the Eastern Cooperative Oncology Group (ECOG) is 0-1;
* Life expectancy of 12 weeks or more;
* According to RECIST 1.1, the subject has at least 1 measurable lesion as the targeted lesion (the only bone metastasis or the only central nervous system metastasis should not be considered as a measurable lesion. A measurable lesion located at the previously irradiated radiation field or other local treatment area should not be selected as targeted lesion, unless the lesion shows unequivocal radiographic progression).

Exclusion Criteria:

* Previous treatment with immune checkpoint agonists (such as CD137 agonists) or immune checkpoint inhibitors (such as CTLA-4, PD-1, PD-L1, LAG3 monoclonal antibody, etc.) or anti-vascular endothelial growth factor (VEGF) target drugs;
* Has uncontrolled or symptomatic brain or spine cord metastases;
* Those who have had other active malignant tumors within 5 years prior to the study treatment, except for those that can be treated locally and have been cured ;
* Poorly controlled hypertension (systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg);
* With a history of hypertensive crisis or hypertensive encephalopathy;
* With a history of abdominal fistula, tracheoesophageal fistula, gastrointestinal perforation, or intra-abdominal abscess within the last 6 months prior to the start of the study treatment;
* Adverse events resulting from prior anti-tumor therapies should be assessed and graded according to the CTCAE 5.0 criteria, subjects whose AEs have not returned to Grade 1 or below;
* Has uncontrollable pleural, pericardial, or abdominal effusions;
* Has received allogeneic hematopoietic stem cell transplantation or organ transplantation.

**Maximum Age:** 70 Years

**Minimum Age:** 18 Years

**Sex:** FEMALE

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** cao.yq@biotheus.com

**Name:** Yanqing Cao

**Phone:** +86 13810452270

**Role:** CONTACT

**Contact 2:**

**Email:** fan.ll@biotheus.com

**Name:** Linlin Fan

**Phone:** +86 18612186005

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Shanghai

**Contacts:**

***Contact 1:***

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

- **Name:** Jian Zhang, professor

- **Role:** CONTACT

**Country:** China

**Facility:** Fudan University Shanghai Cancer Center

#### Overall Officials

**Official 1:**

**Affiliation:** Fudan University

**Name:** Jiong Wu, professor

**Role:** STUDY_CHAIR

**Official 2:**

**Affiliation:** Fudan University

**Name:** Jian Zhang, professor

**Role:** STUDY_CHAIR

### IPD Sharing Statement Module

**Access Criteria:** NCI is committed to sharing data in accordance with NIH policy

**Description:** The data will be published or presented for publications (poster, abstract,articles or papers) or any presentations.

**IPD Sharing:** YES

**Time Frame:** After the trial completed

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000009369

- Term: Neoplasms

- ID: D000001941

- Term: Breast Diseases

- ID: D000012871

- Term: Skin Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M5220

- Name: Breast Neoplasms

- Relevance: HIGH

- As Found: Breast Cancer

- ID: M30373

- Name: Triple Negative Breast Neoplasms

- Relevance: HIGH

- As Found: Triple Negative Breast Cancer

- ID: M5218

- Name: Breast Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M15674

- Name: Skin Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000001943

- Term: Breast Neoplasms

- ID: D000064726

- Term: Triple Negative Breast Neoplasms

### Intervention Browse Module - Ancestors

- ID: D000000972

- Term: Antineoplastic Agents, Phytogenic

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000050257

- Term: Tubulin Modulators

- ID: D000050256

- Term: Antimitotic Agents

- ID: D000050258

- Term: Mitosis Modulators

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M19537

- Name: Paclitaxel

- Relevance: HIGH

- As Found: Surgery

- ID: M231

- Name: Albumin-Bound Paclitaxel

- Relevance: LOW

- As Found: Unknown

- ID: M26197

- Name: Tubulin Modulators

- Relevance: LOW

- As Found: Unknown

- ID: M26196

- Name: Antimitotic Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000017239

- Term: Paclitaxel

### Misc Info Module

- Version Holder: 2024-05-31
