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
Current Sponsor code: S095012
Other descriptive name: PRS-344
Concentration unit: mg/ml milligram
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. Life expectancy of at least 3 months 3. Patient should have a documented disease progression on prior therapy before entry into this study. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 5. Royal Marsden Prognosis score of 0 to 1 (score based on lactate dehydrogenase (LDH) value, albumin value and number of sites of metastasis). 6d. Adequate organ function as assessed by laboratory tests within 7 days prior to pretreatment with obinutuzumab: -Lymphocyte count = 800/µ -Gamma-globulin level > 6g/L (by serum protein electrophoresis) or IgG level > 4g/L (by measurement of quantitative immunoglobulins). 7a A female patient must use a highly effective method of birth control during study treatment and until, for 120 days after the last dose of the study treatment. PRS-344/S095012, or 18 months after the last obinutuzumab infusion, whichever comes the latest. 8a. A male patient with childbearing potential partners must use a condom during the study and for at least 4 months after the last dose of the study treatment., or 6 months after the last Obinutuzumab infusion, whichever comes the latest. 9a. Test should be negative for cytomegalovirus (CMV), Epstein-Barr virus (EBV), Hepatitis B virus (HBV), and Hepatitis C virus (HCV) infection, according to local standards: - Negative CMV DNA testing in serum or plasma by a sensitive quantitative molecular method. - Absence of immunoglobulin (Ig)M antibodies against EBV-VCA (Viral Capside Antigen) - Negative serologic testing for hepatitis B surface antigen (HbsAg) or a negative result by a sensitive quantitative molecular method for HBV-DNA in serum or plasma - Negative HCV RNA testing in serum or plasma by a sensitive quantitative molecular method. 10. Negative test results for human T-lymphotropic virus 1 (HTLV 1). HTLV testing is only required for participants from countries in which HTLV 1 infection is endemic (Japan, countries in the Caribbean basin, South America, Central America, sub-Saharan Africa, and Melanesia). Dose Escalation: 11a. Patients with a histological diagnosis of an unresectable, locally advanced or metastatic solid tumor for which standard treatment options are not available, no longer effective, or not tolerated. 12a. Patients must have measurable disease per RECIST 1.1 as assessed by the local site investigator/imaging. Lesions situated in a previously irradiated area are considered measurable only if progression has been demonstrated in such lesions. 13b. Patients with no available archived material must have one or more tumor lesions amenable to biopsy Dose Expansion: 14. Patients with histologically diagnosed Arm 1 and 2: recurrent, persistent, and/or metastatic cervical cancer. Acceptable histologies are squamous carcinoma, adenocarcinoma, and adenosquamous carcinoma. -Arm 3: locally advanced or metastatic cutaneous squamous cell carcinoma. 15. Patients must have received : Arm 1 (cervical cancer, CPI-naive): at least 1 prior line of platinum based combination therapy. Patients must not have received any prior treatment with an immune checkpoint inhibitor (anti-PD-1, PD-L1 or anti-CTLA-4 [cytotoxic T lymphocyte-associated protein 4]) and do not have access to an approved immune checkpoint inhibitor. Surgery, radiation therapy, and additional chemotherapy must not be considered appropriate alternative treatment options for these patients. Arm 2 (cervical cancer, CPI-relapsed/refractory
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. Chemotherapy, small molecule inhibitors, monoclonal antibodies, antibody-drug conjugates, and/or other similar investigational agent: at least 3 weeks or 5 half-lives prior to first IMP administration, whichever is shorter. b. Radioimmunoconjugates or other similar experimental therapies at least 6 weeks or 5 half-lives prior to first IMP administration, 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. 5c. Patients who have received either systemic corticosteroids (> 10 mg per day or equivalent) or other immunosuppressive medications during the 2 months prior to the first dose of the study drug. Higher single doses of corticosteroids given as premedication against infusion-related reactions are allowed. Treatment with local steroids (inhaled, intranasal, injected are allowed. 6b. Patients with an active infection with a viral, bacterial, or fungal pathogen requiring systemic treatment within seven days before first IMP administration. 7. Patients with a history of an opportunistic infection within a year prior to first IMP administration. 8. History of progressive multifocal leukoencephalopathy. 9. 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 |
|---|---|
| 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) and the recommended phase 2 dose (RP2D) of PRS-344/S095012 Phase 2: To evaluate the potential anti-tumor activity and efficacy of PRS-344/S095012, as per central assessment according to RECIST v1.1 criteria 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 the investigator, according to Response Evaluation Criteria in Solid Tumors (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 further characterize immunogenicity of PRS-344/S095012;Primary end point(s): Phase 1: Incidence of dose-limiting toxicities (DLTs) Incidence and severity of adverse events (AEs) Discontinuation study treatment due to an AE Laboratory, electrocardiogram (ECG) and vital sign measurements Phase 2: -Arms 1 and 2: OR as per central assessment according to RECIST v1.1 criteria -Arm 3: OR as per central assessment and composite response criteria (digital medical photography and/or imaging as per RECIST v1.1) ;Timepoint(s) of evaluation of this end point: DLT: End of cycle 1 Others: All along the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase 1: Serum PK parameters of PRS-344/S095012 Detection of antidrug antibodies (ADA) against PRS-344/S095012 and their titration when applicable Objective Response (OR): Defined as Complete Response (CR) plus Partial Response (PR) 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: All arms: OR as per investigator assessment, Disease Control (DC), DoR, PFS, OS, Time to Response (TTR) AEs, serious adverse events (SAEs), Laboratory, ECG, vital signs Serum concentrations of PRS-344/S095012 Detection of ADA against PRS-344/S095012 and their titration when applicable ;Timepoint(s) of evaluation of this end point: All along the study | — |
Countries
Australia, Belgium, Brazil, France, Spain, Switzerland, United States
Contacts
Public ContactClinical Studies Department
Institut de Recherches Internationales Servier
Outcome results
None listed