Clinical trial NCT05159388: A Study of PRS-344/S095012 (PD-L1x4-1BB Bispecific Antibody-Anticalin Fusion) in Patients With Solid Tumors
Official title: A First in Human Phase 1-2 Open-Label, Multicenter, Dose Escalation and Expansion Study of PRS-344/S095012 in Patients With Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Solid Tumor
Keywords: Solid Tumor = Phase 1/2
Open-label
Dose escalation
Metastatic
PRS-344
S095012
PRS-344/S095012
Anticalin protein
Bi-specific
4-1BB
CD137
PD-L1
Lead sponsor: Servier
Sponsor class: INDUSTRY
Collaborators: name: Institut de Recherches Internationales Servier
First posted: 2021-12-16
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety measurements
timeFrame: 28 days
measure: Safety Measurements
timeFrame: time on trial, average of 6 months
measure: Safety Measurements
timeFrame: time on trial, average of 6 months
measure: Objective Response (OR)
timeFrame: Through study completion up to 24 months
Secondary outcomes:
measure: Mean PRS-344/S095012 concentrations at the end of the infusion
timeFrame: Through study completion up to 24 months
measure: Mean PRS-344/S095012 trough concentrations (Ctrough)
timeFrame: Through study completion up to 24 months
measure: Detection of anti-drug antibodies (ADA) against PRS-344/S095012
timeFrame: Through study completion up to 24 months
measure: Objective Response (OR)
timeFrame: Through study completion up to 24 months
measure: Duration of Response (DoR)
timeFrame: Through study completion up to 24 months
measure: Progression-free Survival (PFS)
timeFrame: Through study completion up to 24 months
measure: Overall Survival (OS)
timeFrame: Through study completion up to 24 months
measure: Disease Control (DC)
timeFrame: Through study completion up to 24 months
measure: Time to Response (TTR)
timeFrame: Through study completion up to 24 months
measure: Safety measurements
timeFrame: time on trial, average of 6 months
measure: Safety measurements
timeFrame: time on trial, average of 6 months
measure: Serum concentrations of PRS-344/S095012
timeFrame: Through study completion up to 24 months
Other outcomes:
Locations:
city: Huntersville
country: United States
facility: Carolina Bio Oncology
state: North Carolina
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: Malvern
country: Australia
facility: Cabrini Oncology Research
state: Victoria
city: Camperdown
country: Australia
facility: Chris O'Brian Lifehouse
city: Woodville South
country: Australia
facility: The Queen Elizabeth Hospital
city: Brussels
country: Belgium
facility: Institute Jules Bordet
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis
city: Gent
country: Belgium
facility: U.Z. Gent Medical Oncology
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: START
city: Madrid
country: Spain
facility: Hospital Universitario Gregorio
Study officials:
References:
citation: 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