Phase 1 Open Label Trial of MST-0312 Alone and in Combination in Subjects With Solid Malignancies (STARLYS)

A Multi-arm, Open-label, Phase 1 Trial to Evaluate the Safety and Tolerability, Pharmacokinetics and Anti-tumour Activity of MST-0312 When Given Alone and in Combination With Anticancer Treatments in Subjects With Solid Malignancies

The STARLYS trial is an adaptive, modular, Phase 1, open-label, multi-part, clinical trial evaluating MST-0312 in selected solid tumors. MST-0312 is a targeted bispecific antibody that is designed to locally stimulate the lymphotoxin beta receptor (LTBR) in order to boost the body's immune response to cancer. The LTBR pathway is important in forming tertiary lymphoid structures and high endothelial venules in tumors, which have been associated with improved patient outcomes. The purpose of this study is to determine the safety and tolerability, pharmacodynamics, pharmacokinetics and anti-tumor activity of MST-0312 in subjects with solid malignancies (initially non-small cell lung cancer (NSCLC), melanoma, bladder cancer, colorectal cancer (CRC) and triple negative breast cancer (TNBC)) when administered either as monotherapy or in combination with anti-cancer treatments (initially pembrolizumab). The STARLYS trial is the first time MST-0312 has been administered to humans.

Study Overview

• Status: Recruiting
• Conditions: Cancer-Neoplasms
• Intervention / Treatment: Drug: MST-0312; Drug: Pembrolizumab

• Study Type: Interventional
• Enrollment (Estimated): 157
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Mestag MST-0312-1001; Phone Number: +447721893628; Email: medical@mestagtx.com

Study Locations

• Spain
  • Barcelona, Spain, 08035
    • Not yet recruiting
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28027
    • Not yet recruiting
    • Clinica Universidad de Navarra
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Universitario Fundación Jiménez Díaz
  • Madrid, Spain, 28041
    • Not yet recruiting
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28050
    • Recruiting
    • Hospital Universitario Hm Sanchinarro
  • Valencia, Spain, 46010
    • Not yet recruiting
    • Hospital Clinico Universitario De Valencia

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male and female subjects of any ethnic origin, aged 18 years and over.
• Must have given written informed consent and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects.
• Subject must have a solid malignancy (non-small cell lung cancer (NSCLC), melanoma, bladder cancer, colorectal cancer (CRC) and triple negative breast cancer (TNBC)).
• An ECOG performance status of 0 or 1 with no deterioration over the previous two weeks.
• Willing to permit access to stored historical tumour tissue and prior tumour radiological assessments, cancer treatment history, including response to treatment, and tumour biomarker data, where available.
• Willing and able to comply with all scheduled visits, treatment plans, laboratory tests, and other trial procedures.

Exclusion Criteria:

• Any unresolved toxicity (except alopecia) from prior therapy of ≥2 CTCAE Grade.
• Active or documented history of autoimmune disease requiring interventional therapy.
• Active infection requiring systemic antibiotic, antifungal, or antiviral medication within 14 days prior to first dose of IMP.
• Male or female subjects of childbearing potential unwilling to comply with contraception requirements.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Module 1A; MST-0312 monotherapy dose escalation	Drug: MST-0312; A complete treatment cycle is defined as 21 calendar days.
Experimental: Module 1B; MST-0312 monotherapy backfill	Drug: MST-0312; A complete treatment cycle is defined as 21 calendar days.
Experimental: Module 2A; MST-0312 plus pembrolizumab dose escalation	Drug: MST-0312; A complete treatment cycle is defined as 21 calendar days.; Drug: Pembrolizumab; Monoclonal antibody; Other Names: Keytruda
Experimental: Module 2B; MST-0312 plus pembrolizumab backfill	Drug: MST-0312; A complete treatment cycle is defined as 21 calendar days.; Drug: Pembrolizumab; Monoclonal antibody; Other Names: Keytruda
Experimental: Module 2C; MST-0312 plus pembrolizumab expansion	Drug: MST-0312; A complete treatment cycle is defined as 21 calendar days.; Drug: Pembrolizumab; Monoclonal antibody; Other Names: Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of Dose-limiting Toxicities (DLTs)	From baseline to end cycle 1. A complete treatment cycle is defined as 21 calendar days.
Incidence of Adverse Events, Treatment Emergent Adverse Events, Serious Adverse Events measured by Criteria for Adverse Events Version 6.0 (CTCAE v6.0)	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum Concentration (Cmax) Derived for MST-0312	24 months
Time of Maximum Concentration (Tmax)	24 Months
Area Under the Curve (AUC) for Various Time Intervals	24 Months
Half Life (t1/2) for MST-0312	24 Months
Clearance (CL) for MST-0312	24 Months
Percentage of Participants with Anti-Drug Antibodies (ADAs)	24 Months
Objective Response Rate (ORR) by RECIST 1.1 and iRECIST	12 Months
Disease Control Rate (DCR) by RECIST 1.1 and iRECIST	12 Months
Duration of Response (DoR) by RECIST 1.1 and iRECIST	12 Months
Progression Free Survival (PFS) by RECIST 1.1 and iRECIST	12 Months
Best Overall Response (BoR) by RECIST 1.1 and iRECIST	12 Months
Time To Response (TTR) by RECIST 1.1 and iRECIST	12 Months
Progression Free Survival 2 (PFS2) by RECIST 1.1 and iRECIST	48 Months
Overall Survival (OS)	48 Months

Collaborators and Investigators

• Sponsor: Mestag Therapeutics Limited

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: May 14, 2026
• First Submitted That Met QC Criteria: May 20, 2026
• First Posted (Actual): May 28, 2026

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: pembrolizumab
• Other Study ID Numbers: MST-0312-1001; 2025-524446-10 (EudraCT Number)

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