A Study of STRO-002 in Chinese Adults With Epithelial Ovarian Cancer and Other Advanced Malignant Solid Tumors

A Phase I/IIa Study to Evaluate the Safety, Tolerability , Pharmacokinetics and Preliminary Efficacy of STRO-002 in Chinese Adults With Advanced Epithelial Ovarian Cancer, Endometrial Cancer, and Other Advanced Malignant Solid Tumors.

This is a multi-center, open-label, monotherapy dose escalation, PK bridging, and dose expansion Phase I/IIa study in Chinese adult subjects to evaluate the safety, tolerability, Pharmacokinetics (PK) profiles, immunogenicity, and preliminary efficacy of STRO-002 in patients with advanced malignant solid tumors.

Study Overview

• Status: Recruiting
• Conditions: Neoplasm Malignant
• Intervention / Treatment: Biological: STRO-002

Detailed Description

This study consists of two parts, Phase I (dose escalation and PK bridging) and Phase IIa (dose expansion). Subjects in each cohort of Phase I will be administered 3 scheduled dose levels of STRO-002 as monotherapy by intravenous infusion until intolerable toxicity, radiographic disease progression, or subject withdrawal for other reasons. 5 dose arms are tentatively set based on the available safety, PK and efficacy data of STRO-002 for the Phase IIa (dose expansion).

• Study Type: Interventional
• Enrollment (Estimated): 132
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Kongli zhu; Phone Number: +8615800363686; Email: tsl-zhukongli@tasly.com

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China
      • Recruiting
      • West China Hospital of Sichuan University
      • Contact: Li Zheng, MD; Phone Number: +8618980601950; Email: lzheng2005618@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Life expectancy >3 months.
2. Subjects must have at least one measurable lesion (non-radiotherapy field) per RECIST v1.1.
3. The adverse reactions (ARs) of previous anti-tumor therapy must recover to NCI CTCAE v5.0 grade ≤ 1 (except for toxicity with no safety risks judged by investigators, such as alopecia).
4. For adequate bone marrow reserve and organ function.
5. Calculated QT interval corrected for heart rate using Fridericia correction formula (QTcF), screening and C1D1 predose ECG must be < 500 msec.
6. (Dose escalation + PK bridging)Relapsed and/or progressed at least one prior line of standard of care, or have no available standard of care, or are intolerable to standard of care, or have no further approved treatment options available.
7. (Dose expansion)For each cohort, the following criteria should be met: a. Cohorts A and B (ovarian cancer): High-grade serous epithelial ovarian cancer with a confirmed pathological diagnosis, fallopian tube cancer, or primary peritoneal carcinoma.b. Cohort C (endometrial cancer): Endometrial epithelial cancer with a confirmed pathological diagnosis (endometrioid adenocarcinoma; serous adenocarcinoma; undifferentiated carcinoma; mixed epithelial carcinoma; or adenocarcinoma not otherwise specified [N.O.S]), and the disease has relapsed or progressed after at least 1-line of platinum-based chemotherapy regimen or 1-line of immunotherapy-containing regimen, and no more than 3 lines of treatment regimen received previously. c. Cohort D (non-small-cell lung cancer): Unresectable locally advanced or metastatic non-small-cell lung cancer with a confirmed pathological diagnosis, and previous treatment meets the following criteria: - Patients without genetic mutations: If they receive 1-line platinumdoublet chemotherapy and anti-PD-1/PD-L1 combination at the same time, they have previously received at least 1-line treatment in the past and totally no more than 4 lines of treatment regimen; if they have received platinum-doublet chemotherapy sequentially and anti-PD-1/PD-L1, they have previously received at least 2-line treatment and totally no more than 4 lines of treatment regimen. - People with genetic mutations: Received at least 1-line approved targeted therapy, and previously no more than 4 lines of treatment regimen. d. Cohort E (triple-negative breast cancer): Unresectable locally advanced or metastatic breast cancer with a confirmed pathological diagnosis, and the ER, PR, and HER-2 are all negative. ER and PR negative are defined as: IHC ER < 1%, IHC PR < 1%. HER-2 negative is defined as: IHC HER-2 (-) or (1+). Patients with HER-2 (2+) must undergo FISH testing and the result is negative; they have previously received at least 1 line but no more than 4 lines of systemic anticancer therapy.

Exclusion Criteria:

1. Prior treatment with ADCs containing tubulin inhibitors (e.g., mirvetuximab of Immunogen, XMT-1536 of Mersana, which contains auristain derivatives that inhibit tubulin polymerization).
2. Previous treatment with other FolRα-targeting drugs.
3. History of severe allergy or anaphylactic reaction to monoclonal antibody therapy or antibody-related fusion protein treatment.
4. Prior anticancer therapy (prior to initial dose of study drug): Chemotherapy within 3 weeks, PARPi within 2 weeks, other therapeutic anticancer antibodies within 3 weeks, radio- or toxin-immunoconjugate (such as ADCs) within 10 weeks, Chinese herbal medicine or traditional Chinese medicinal products with anti-tumor indications within 1 week, radion therapy/major surgery within 4 weeks (the definition of surgery refers to Grade 3-4 surgeries specified in the Measures for the Grade Management of Surgery in Medical Institutions issued by the National Health Commission of the PRC on December 06, 2022) or are in the recovery period from surgery (the investigator judges that there are still risks in participating the clinical study). 5. Pre-existing clinically significant ocular disorders including, but not limited to: Active or chronic corneal disorders, history of corneal transplantation, or active ocular conditions requiring ongoing treatment/monitoring, such as uncontrolled glaucoma, wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, macular degeneration, presence of papilledema and/or visual acuity reduced, Prior anticancer therapy (prior to initial dose of study drug): Chemotherapy within 3 weeks, PARPi within 2 weeks, other therapeutic anticancer antibodies within 3 weeks, radio- or toxin-immunoconjugate (such as ADCs) within 10 weeks, Chinese herbal medicine or traditional Chinese medicinal products with anti-tumor indications within 1 week, radion therapy/major surgery within 4 weeks (the definition of surgery refers to Grade 3-4 surgeries specified in the Measures for the Grade Management of Surgery in Medical Institutions issued by the National Health Commission of the PRC on December 06, 2022) or are in the recovery period from surgery (the investigator judges that there are still risks in participating the clinical study).
5. Pre-existing clinically significant ocular disorders including, but not limited to: Active or chronic corneal disorders, history of corneal transplantation, or active ocular conditions requiring ongoing treatment/monitoring, such as uncontrolled glaucoma, wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, macular degeneration, presence of papilledema and/or visual acuity reduced, blurred vision, conjunctivitis, keratitis, cataracts with significant visual impairment, uveitis, Sjogren syndrome, and dry eye.

Patients who are required to take folic acid-containing supplements, e.g., folate deficiency.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1(Phase I); STRO-002 3.5 mg/kg Open Lable	Biological: STRO-002; STRO-002 is an Antibody-drug conjugates (ADCs) combine the specificity of monoclonal antibodies with the anti-tumor activity of cytotoxic drugs.
Experimental: Cohort 2(Phase I); STRO-002 4.3 mg/kg Open Lable	Biological: STRO-002; STRO-002 is an Antibody-drug conjugates (ADCs) combine the specificity of monoclonal antibodies with the anti-tumor activity of cytotoxic drugs.
Experimental: Cohort 3(Phase I); STRO-002 5.2 mg/kg Open Lable	Biological: STRO-002; STRO-002 is an Antibody-drug conjugates (ADCs) combine the specificity of monoclonal antibodies with the anti-tumor activity of cytotoxic drugs.
Experimental: Cohort A(Phase IIa); Recurrent and/or progressive ovarian epithelial cancer, confirmed by immunohistochemistry [IHC] testing with FolRα positive expression (TPS ≥ 75%).	Biological: STRO-002; STRO-002 is an Antibody-drug conjugates (ADCs) combine the specificity of monoclonal antibodies with the anti-tumor activity of cytotoxic drugs.
Experimental: Cohort B(Phase IIa); Recurrent and/or progressive ovarian epithelial cancer, confirmed by IHC testing with FolRα positive expression (25% ≤ TPS < 75%).	Biological: STRO-002; STRO-002 is an Antibody-drug conjugates (ADCs) combine the specificity of monoclonal antibodies with the anti-tumor activity of cytotoxic drugs.
Experimental: Cohort C(Phase IIa); Recurrent and/or progressive endometrial cancer, confirmed by IHC testing with FolRα positive expression (TPS ≥ 25%).	Biological: STRO-002; STRO-002 is an Antibody-drug conjugates (ADCs) combine the specificity of monoclonal antibodies with the anti-tumor activity of cytotoxic drugs.
Experimental: Cohort D(Phase IIa); Recurrent and/or progressive non-small-cell lung cancer, confirmed by IHC testing with FolRα positive expression (TPS ≥ 25%).	Biological: STRO-002; STRO-002 is an Antibody-drug conjugates (ADCs) combine the specificity of monoclonal antibodies with the anti-tumor activity of cytotoxic drugs.
Experimental: Cohort E(Phase IIa); Recurrent and/or progressive triple-negative breast cancer, confirmed by IHC testing with FolRα positive expression (TPS ≥ 25%).	Biological: STRO-002; STRO-002 is an Antibody-drug conjugates (ADCs) combine the specificity of monoclonal antibodies with the anti-tumor activity of cytotoxic drugs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DLT Assessment	Toxicity associated with the treatment of the investigational drug STRO-002.	From Day1 to Day21 after first dose of STRO-002
AE Assessment	The frequency of AE	From first dose of STRO-002 until 28 days after the last dose of STRO-002
AUC	PK parameter：area under the concentration-time curve (AUC)	From first dose of STRO-002 until 28 days after the last dose of STRO-002.
Cmax	PK parameter：Cmax	From first dose of STRO-002 until 28 days after the last dose of STRO-002.
Half life (t1/2)	PK parameter：half life (t1/2)	From first dose of STRO-002 until 28 days after the last dose of STRO-002.
Overall response rate (ORR)	ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) per RECIST v 1.1	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Determine the recommended phase II dose (RP2D)		From first dose of STRO-002 until 28 days after the last dose of STRO-002.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of positive anti-drug antibodies (ADAs) and changes over time.	Occurrence of positive anti-drug antibodies (ADAs)	From first dose of STRO-002 until 28 days after the last dose of STRO-002.
Duration of response (DOR)	DOR is defined as the time from the first documented response (CR or PR evaluated by RECIST v1.1) until the time of first documentation of disease progression by RECIST v1.1.	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Progression-free survival (PFS)	PFS is defined as a time from the first dose of STRO-002 to documented disease progression or death from any cause.	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
FolRα and cancer antigen 125 (CA-125) levels measured in tumor tissue	A CA-125 response is defined as at least a 50% reduction in CA-125 levels from a pretreatment sample, and the response must be confirmed and maintained for at least 28 days.	From first dose of STRO-002 until 28 days after the last dose of STRO-002.

Collaborators and Investigators

• Sponsor: Tasly Pharmaceutical Group Co., Ltd
• Collaborators: Sutro Biopharma, Inc.
• Investigators: Study Chair: Kongli zhu, Tasly Pharmaceutical Group Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2023
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: November 21, 2023
• First Submitted That Met QC Criteria: February 1, 2024
• First Posted (Actual): February 2, 2024

Study Record Updates

• Last Update Posted (Actual): February 2, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: advanced malignant solid tumors
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Neoplasms; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: TSL-B2276-1-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No