A Study of PRS-344/S095012 (PD-L1x4-1BB Bispecific Antibody) in Patients With Solid Tumors

A First in Human Phase 1-2 Open-Label, Multicenter, Dose Escalation and Expansion Study of PRS-344/S095012 in Patients With Solid Tumors

This is a first-in-human (FIH), phase 1/2, multi center, open-label, dose escalation and cohort expansion study designed to determine the safety and tolerability of PRS-344/S095012 in patients with advanced and/or metastatic solid tumors.

Study Overview

• Status: Terminated
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: PRS-344/S095012

Detailed Description

The trial is an open-label, multi-center safety trial of PRS-344/S095012. The trial consists of two parts, a dose escalation part (phase 1, first-in-human (FIH) and an expansion part (phase 2)). The expansion part of the trial will be initiated once the optimal biological dose (OBD) has been determined. The study was terminated during phase 1 and thus, recruitment into phase 2 was not started.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Camperdown, Australia
    • Chris O'Brian Lifehouse
  • Woodville South, Australia
    • The Queen Elizabeth Hospital
  • Victoria
    • Malvern, Victoria, Australia
      • Cabrini Oncology Research
• Belgium
  • Brussels, Belgium
    • Institute Jules Bordet
  • Edegem, Belgium
    • Universitair Ziekenhuis
  • Ghent, Belgium
    • U.Z. Gent Medical Oncology
• Spain
  • Barcelona, Spain
    • Hospital Vall d'Hebron
  • Madrid, Spain, 28050
    • START
  • Madrid, Spain
    • Hospital Universitario Gregorio
• United States
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Carolina Bio Oncology
  • Texas
    • San Antonio, Texas, United States, 78229
      • NEXT Oncology

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥18 years on the day the consent is signed.
2. Patients with histologically confirmed diagnosis of unresectable, locally advanced or metastatic solid tumor for which standard treatment options are not available, no longer effective, or not tolerated.
3. Patient should have a documented disease progression on prior therapy before entry into this study.
4. Patients must have at least one measurable target lesion as per RECIST 1.1.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Patient with no available archived material must have one or more tumor lesions amenable to biopsy.
7. Adequate organ function as assessed by laboratory tests within 7 days prior to pretreatment with obinutuzumab.
8. A female patient must use a highly effective method of birth control during study treatment and for 120 days after last dose of PRS-344/S095012, or 18 months after the last obinutuzumab infusion, whichever comes the latest.

Exclusion Criteria:

1. Patients with previously treated brain metastases may participate provided they are radiologically stable, clinically asymptomatic and are off immunosuppressive therapies for at least 4 weeks. Low dose of steroid <10 mg/day prednisone or equivalent) is allowed.

2. Patients who have received prior:

   1. Small molecule inhibitors, and/or other similar investigational agent: ≤ 2 weeks or 5 half-lives, whichever is shorter.
   2. Chemotherapy, other monoclonal antibodies, antibody-drug conjugates, or other similar experimental therapies: ≤3 weeks or 5 half-lives, whichever is shorter.
   3. Radioimmunoconjugates or other similar experimental therapies ≤6 weeks or 5 half-lives, whichever is shorter.
3. Patients who have received 4-1BB agonists in the past.
4. Patients who had a major surgery within 4 weeks prior to first administration of IMP.
5. History of progressive multifocal leukoencephalopathy.
6. Active tuberculosis requiring treatment within 3 years prior to the start of treatment or a suspicion of latent tuberculosis by the investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PRS-344/S095012	Drug: PRS-344/S095012; PRS-344/S095012 Monotherapy or with pretreatment by obinutuzumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Measurements: Number of Participants With at Least One DLT in the First 28-days of Treatment	Phase 1: Dose-limiting toxicities (DLTs) over the first 28-days of study treatment	28 days
Safety Measurements: Number of Participants With at Least One AE	Phase 1: Adverse events (AEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0	Through study termination, approximately 3.5 years
Safety Measurements: Number of Participants With at Least One AE Leading to Treatment Discontinuation	Phase 1: Discontinuation of study treatment due to an AE	Through study termination, approximately 3.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean PRS-344/S095012 Concentrations at the End of the Infusion	Phase 1	Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle was 28 days)
Mean PRS-344/S095012 Trough Concentrations (Ctrough)	Phase 1	Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 3 Day 15, Cycle 4 Day 1, Cycle 4 Day 15, Cycle 5 Day 1, Cycle 5 Day 15, Cycle 6 Day 1 (each cycle was up to 28 days)
Number of Participants With at Least One Positive Anti-drug Antibody (ADA) Titer Result PRS-344/S095012	Phase 1	Through study termination, approximately 3.5 years
Objective Response Rate (ORR)	Phase 1: Defined as Complete Response (CR) plus Partial Response (PR), per investigator assessment	Through study termination, approximately 3.5 years
Best Overall Response (BOR)	Phase 1: The best response across visits as; 1) partial response (PR): At least 2 PR or better (PR followed by PR or PR followed by CR) at least 4 weeks apart and not qualifying for a complete response (CR), 2) stable disease (SD): At least 1 SD assessment (or better) ≥ 43 days (assuming an 8-week scan interval with a 14-day visit window) after start of study treatment and not qualifying for CR or PR, 4) progressive disease (PD): Documentation of PD after start of study treatment (and not qualifying for CR, PR, or SD), 5) non-evaluable (NE): All other cases.	Through study termination, approximately 3.5 years
Best Tumor Shrinkage From Baseline	Phase 1: The best shrinkage value for the target lesion from baseline	Through study termination, approximately 3.5 years

Collaborators and Investigators

• Sponsor: Servier Bio-Innovation LLC
• Collaborators: Institut de Recherches Internationales Servier
• Investigators: Study Director: Tim Demuth, MD, PhD, Pieris Pharmaceuticals

Publications and helpful links

General Publications

• Jungels C, Kotecki N, Calvo E, Garralda E, Price T, Zahn X, Abbas A, Mahnke L, Rauschning W, Morales-Kastresana A, Lucia Pattarini L, Bossenmaier B, Scholer-Dahirel A, Demuth T, Legrande J. Abstract CT255: Study of PRS-344/S095012 a PD-L1/4-1BB bispecific antibody-Anticalin®-fusion in patients with solid tumors. Canc Res. 2022 Jun 15;82(12_Supplement):CT255. doi: https://doi.org/10.1158/1538-7445.AM2022-CT255

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2021
• Primary Completion (Actual): April 1, 2025
• Study Completion (Actual): April 1, 2025

Study Registration Dates

• First Submitted: November 15, 2021
• First Submitted That Met QC Criteria: December 2, 2021
• First Posted (Actual): December 16, 2021

Study Record Updates

• Last Update Posted (Actual): June 16, 2026
• Last Update Submitted That Met QC Criteria: June 15, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Open-label; Metastatic; Dose escalation; PD-L1; CD137; 4-1BB; Bi-specific; Solid Tumor = Phase 1/2; PRS-344; S095012; PRS-344/S095012; Anticalin protein
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis
• Other Study ID Numbers: CL1-95012-001; 2023-510046-25-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.

Access can be requested for all interventional clinical studies:

• used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
• where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.

In addition, access can be requested for all interventional clinical studies in patients:

• sponsored by Servier
• with a first patient enrolled as of 1 January 2004 onwards
• for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.

• IPD Sharing Time Frame: After Marketing Authorization in EEA or US if the study is used for the approval.
• IPD Sharing Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

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