Study to Assess an Anti-Trop2 Antibody Drug Conjugate in Relapsed or Refractory Solid Tumors

A Phase 1B, Dose-Escalation Study of the Safety and Preliminary Efficacy of an Anti-Trop2 Antibody Drug Conjugate (STI-3258) in Patients With Relapsed or Refractory Solid Tumors

This is a phase 1b, open-label, dose-escalation study o STI-3258 administered intravenously in subjects with relapsed or refractory solid tumors.

Study Overview

• Status: Withdrawn
• Conditions: Solid Tumor, Adult; Refractory Cancer; Relapsed Solid Neoplasm
• Intervention / Treatment: Biological: STI-3258

Detailed Description

This is a Phase 1b, open-label, dose-escalation study o STI-3258 administered intravenously in subjects with relapsed or refractory solid tumors including ovarian, breast, lung, esophageal, gastric, hepatocellular and urothelial cancers.

The study will determine any dose limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), assessing safety and preliminary efficacy using ascending dose cohorts and a conventional 3+3 study design.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Mike Royal, MD; Phone Number: (858)203-4100; Email: mroyal@sorrentotherapeutics.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically or cytologically confirmed advanced cancer that is relapsing or refractory to at least one prior treatment and not a candidate for other treatments or is intolerant to established treatments.
• At least one measurable disease per Response Evaluation Criteria in Solid Tumors v. 1.1 (RECIST 1.1).
• Eastern Cooperative Oncology Group Performance Status ≤ 2.
• Must have a life expectancy of ≥ 6 months.
• Must have adequate bone marrow, hepatic and renal function as assessed by specific laboratory tests.
• Must be recovered ≤ Grade 1 from acute toxicities from previous therapies, excluding alopecia and vitiligo.
• Has not had prior treatment within 2 weeks of screening with high dose corticosteroids.
• Be willing and able to comply with the study schedule and all study requirements.
• Willing to follow all contraception guidelines.

Exclusion Criteria:

• Previous treatment with any systemic therapy or investigational drug within 2 weeks of the first dose of study drug.
• Currently participating in any other interventional clinical study.
• Has a diagnosis of other malignancies if the malignancy has required therapy within the last 3 years or is not in complete remission.
• Has presence of bulky disease defined as any mass > 7 cm in greatest dimension will trigger a discussion with the medical monitor.
• Has left ventricular ejection fraction (LVEF) < 40%.
• New York Heart Association (NYHA) Class ≥ 3.
• Has prolonged QTcF interval on an electrocardiogram.
• Has spinal cord compression or clinically active brain metastases.
• Has a history of Sacituzumab govitecan treatment.
• History of anaphylactic reaction to irinotecan or ≥ Grade 3 toxicity to prior irinotecan treatment.
• Has active or prior COVID-19 infection, with symptoms presenting within 4 weeks of the first dose of study drug.
• Has an active bacterial, viral, or fungal infection.
• Is currently pregnant or breast feeding or planning on either during the study.
• Has chronic or moderate chronic obstructive pulmonary disease or other chronic respiratory conditions unless receiving treatment and stable for 3 months prior to screening.
• Has known HIV or acquired immunodeficiency syndrome-related illness, acute or history of chronic hepatitis B or C.
• Has any significant medical condition, abnormality, or psychiatric illness that would prevent study participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: STI-3258; Intravenous infusion to be given with prophylaxis for infusion reactions, evaluating up to five dose cohorts including: 8 mg/kg, 12 mg/kg, 16 mg/kg, 20 mg/kg, and 24 mg/kg.	Biological: STI-3258; Intravenous infusion of STI-3258 will be given (one infusion every three weeks).; Other Names: anti-Trop2-SN38 antibody drug conjugate (ADC)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events by type, frequency, severity, and causality (safety)	Safety as assessed by incidence of adverse events (AEs) by type, frequency, severity, and causality	Baseline through study completion at up to approximately 24 months
Incidence of serious adverse events by type, frequency, severity, and causality (safety)	Safety as assessed by incidence of serious AEs (SAEs) by type, frequency, severity, and causality	Baseline through study completion at up to approximately 24 months
Incidence of dose-limiting toxicities (safety)	Safety as assessed by incidence of dose-limiting toxicities	Baseline through study completion at up to approximately 24 months
Incidence of treatment-emergent adverse events by type, frequency, severity, and causality (safety)	Safety as assessed by incidence of treatment-emergent AEs (TEAEs) by type, frequency, severity, and causality	Baseline through study completion at up to approximately 24 months
Incidence of Infusion-related adverse events by type, frequency, severity, and causality (safety)	Safety as assessed by incidence of Infusion-related AEs (IrAEs) by type, frequency, severity, and causality	Baseline through study completion at up to approximately 24 months
Determine the MTD	Determine the MTD of STI-3258	Baseline through study completion at up to approximately 24 months
Determine the RP2D	To determine the RP2D of STI-3258	Baseline through study completion at up to approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess preliminary efficacy of STI-3258	To assess the preliminary efficacy of STI-3258 in the treatment of patients with RRSTs based upon Response evaluation criteria in solid tumors (RECIST).	Baseline through study completion at up to approximately 24 months
Assess the area under the curve (AUC) pharmacokinetic profile of STI-3258	To assess the AUC of STI-3258 in plasma as a measure of exposure to the ADC, STI-3258.	Baseline through study completion at up to approximately 24 months

Collaborators and Investigators

• Sponsor: Sorrento Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2022
• Primary Completion (Anticipated): May 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: August 20, 2021
• First Submitted That Met QC Criteria: September 17, 2021
• First Posted (Actual): September 29, 2021

Study Record Updates

• Last Update Posted (Estimate): January 26, 2023
• Last Update Submitted That Met QC Criteria: January 24, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: relapsed or refractory solid tumors
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Immunoconjugates
• Other Study ID Numbers: T2ADC-RRST-101

Drug and device information, study documents

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