Solid Tumor
Conditions
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
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. The study was terminated during phase 1 and thus, recruitment into phase 2 was not started.
Interventions
DRUGPRS-344/S095012
PRS-344/S095012 Monotherapy or with pretreatment by obinutuzumab
Sponsors
Servier Bio-Innovation LLC
Institut de Recherches Internationales Servier
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety Measurements: Number of Participants With at Least One DLT in the First 28-days of Treatment | 28 days | Phase 1: Dose-limiting toxicities (DLTs) over the first 28-days of study treatment |
| Safety Measurements: Number of Participants With at Least One AE | Through study termination, approximately 3.5 years | Phase 1: Adverse events (AEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 |
| Safety Measurements: Number of Participants With at Least One AE Leading to Treatment Discontinuation | Through study termination, approximately 3.5 years | Phase 1: Discontinuation of study treatment due to an AE |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean PRS-344/S095012 Concentrations at the End of the Infusion | Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle was 28 days) | Phase 1 |
| Mean PRS-344/S095012 Trough Concentrations (Ctrough) | 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) | Phase 1 |
| Number of Participants With at Least One Positive Anti-drug Antibody (ADA) Titer Result PRS-344/S095012 | Through study termination, approximately 3.5 years | Phase 1 |
| Objective Response Rate (ORR) | Through study termination, approximately 3.5 years | Phase 1: Defined as Complete Response (CR) plus Partial Response (PR), per investigator assessment |
| Best Overall Response (BOR) | Through study termination, approximately 3.5 years | 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. |
| Best Tumor Shrinkage From Baseline | Through study termination, approximately 3.5 years | Phase 1: The best shrinkage value for the target lesion from baseline |
Countries
Australia, Belgium, Spain, United States
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 59.8 years STANDARD_DEVIATION 12.21 |
| Age, Customized <65 years | 28 Participants |
| Age, Customized ≥65 years | 18 Participants |
| Race and Ethnicity Not Collected | 0 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 4 | 5 / 9 | 14 / 14 | 3 / 6 | 8 / 13 |
| other Total, other adverse events | 4 / 4 | 9 / 9 | 14 / 14 | 6 / 6 | 12 / 12 |
| serious Total, serious adverse events | 1 / 4 | 8 / 9 | 12 / 14 | 3 / 6 | 11 / 12 |
Outcome results
None listed