Advanced and/or metastatic solid tumors MedDRA version: 21.1 Level: LLT Classification code 10065252 Term: Solid tumor System Organ Class: 100000004864
Conditions
Interventions
Product Name: S095012
Product Code: S095012
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: S095012/PRS-344
Current Sponsor code: S095012
Other descriptive name: PRS-34
Sponsors
Institut de Recherches Internationales Servier
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age =18 years on the day the consent is signed. 2. Dose escalation and back-fill cohorts: 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 72 hours prior to the start of treatment. Dose Expansion: 8. Patients who have had prior checkpoint inhibitor (CPI) treatment in the past 6 months must have documented confirmed radiographic progression from it prior to study entry. 9. Patients with histologically diagnosed extensive stage small cell lung cancer or locally advanced or metastatic squamous cell carcinoma of the esophagus. 10. Patients must have received and progressed on only one prior regimen in the metastatic setting comprising an PD-(L)1 plus chemotherapy. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 110 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 51
Exclusion criteria
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: a. Small molecule inhibitors, and/or other similar investigational agent: = 2 weeks or 5 half-lives, whichever is shorter. b. Chemotherapy, other monoclonal antibodies, antibody-drug conjugates, or other similar experimental therapies: = 3 weeks or 5 half-lives, whichever is shorter. c. 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. Dose Expansion: 5. Patient who received therapy with an irinotecan containing regimen 6. Patients must not be on warfarin, strong cytochrome P450 (CYP) 3A4 inducers, strong CYP3A4 inhibitors, or strong UGT1A1 inhibitors.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1: To evaluate the safety and tolerability profile of single-agent PRS-344/S095012 To determine the maximum tolerated dose (MTD) if determined, or maximum administered dose (MAD) of PRS-344/S095012 Phase 2: To evaluate the anti-tumor activity and efficacy of PRS-344/S095012, based on appropriate clinical standards for the specified tumor type.;Secondary Objective: Phase 1: To characterize the pharmacokinetics (PK) of PRS-344/S095012 To evaluate the immunogenicity of PRS 344/S095012 To assess the preliminary anti-tumor activity of PRS-344/S095012 as per RECIST v1.1 Phase 2: To further describe the efficacy, through survival, duration of responses, clinical benefit To further characterize the safety and tolerability of PRS-344/S095012 in specific indications To further characterize the PK profile of PRS-344/S095012 To evaluate those biomarkers potentially predictive of response from tumor and blood samples;Primary end point(s): Phase 1: Incidence of dose-limiting toxicities (DLTs) Incidence and severity of adverse events (AEs) Discontinuing study treatment due to an AE Laboratory, ECG and vital sign measurements Phase 2: Objective Response Rate (ORR) : proportion of patients who have Complete Response (CR) or Partial Response (PR);Timepoint(s) of evaluation of this end point: DLT: End of cycle 1 Others: All along the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: All along the study;Secondary end point(s): Phase 1: Serum PK parameters of PRS-344/S095012 Presence of antidrug antibody (ADA), ORR Duration of Response (DOR): time from first demonstration of response to progression or death, whichever occurs first. Progression-free Survival (PFS): time from the first dose of treatment to first documented disease progression or death due to any cause, whichever occurs first. Overall Survival (OS): time from first dose of study drug to death due to any cause. Phase2: DCR, DOR, PFS, OS AEs, SAEs, Laboratory, ECG, vital signs Serum PK parameters of PRS-344/S095012 PD-L1, 4-1BB, and CD8 expression in the tumor Tumor mutational burden (TMB), in the tumor and/or blood, MSI status, specific mutations Gene expression profiling in the tumor and/or blood | — |
Countries
Australia, Belgium, France, Spain, United States
Contacts
Public ContactDpto. de Investigación y Desarrollo
Laboratorios Servier S.L.
Outcome results
None listed