A Study of PRS-344/S095012 (PD-L1x4-1BB Bispecific Antibody-Anticalin Fusion) 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: Completed
• 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.

• Study Type: Interventional
• Enrollment (Actual): 45
• 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
  • Gent, 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety measurements	Phase 1: Incidence of dose-limiting toxicities (DLTs) over the first 28-days of study treatment	28 days
Safety Measurements	Phase 1: Incidence of adverse events (AEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0	time on trial, average of 6 months
Safety Measurements	Phase 1: Discontinuation of study treatment due to an AE	time on trial, average of 6 months
Objective Response (OR)	Phase 2: Defined as Complete Response (CR) plus Partial Response (PR). For arms 1 and 2, per central assessment according to RECIST v1.1 criteria. For Arm 3, per central assessment and composite response criteria (digital medical photography and/or imaging as per RECIST v1.1)	Through study completion up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean PRS-344/S095012 concentrations at the end of the infusion	Phase 1	Through study completion up to 24 months
Mean PRS-344/S095012 trough concentrations (Ctrough)	Phase 1	Through study completion up to 24 months
Detection of anti-drug antibodies (ADA) against PRS-344/S095012	Phase 1 and 2	Through study completion up to 24 months
Objective Response (OR)	Phase 1 and 2: Defined as Complete Response (CR) plus Partial Response (PR), per investigator assessment	Through study completion up to 24 months
Duration of Response (DoR)	Phase 1 and 2: Defined as the time from first demonstration of response to progression or death, whichever occurs first	Through study completion up to 24 months
Progression-free Survival (PFS)	Phase 1 and 2: Defined as the time from the first dose of treatment to first documented disease progression or death due to any cause, whichever occurs first	Through study completion up to 24 months
Overall Survival (OS)	Phase 1 and 2: Defined as the time from first dose of study drug to death due to any cause	Through study completion up to 24 months
Disease Control (DC)	Phase 2: The proportion of patients who achieved SD, PR, or CR (based on patient's best response)	Through study completion up to 24 months
Time to Response (TTR)	Phase 2: The time from the first dose of PRS-344/S095012 to the first documentation of CR or PR	Through study completion up to 24 months
Safety measurements	Phase 2: Incidence of adverse events (AEs)	time on trial, average of 6 months
Safety measurements	Phase 2: Incidence of serious adverse events (AEs)	time on trial, average of 6 months
Serum concentrations of PRS-344/S095012	Phase 2	Through study completion up to 24 months

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 8, 2025
• Study Completion (Actual): April 8, 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 (Estimated): July 8, 2025
• Last Update Submitted That Met QC Criteria: July 7, 2025
• Last Verified: July 1, 2025

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: Neoplasms
• Other Study ID Numbers: CL1-95012-001; 2019-003456-36 (EudraCT Number)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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