Locally advanced/metastatic endometrial carcinoma or cervix carcinoma progressing/relapsing after at least one prior systemic chemotherapy. MedDRA version: 21.1 Level: PT Classification code 10014734 Term: Endometrial cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: PT Classification code 10014733 Term: Endometrial cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (in
Conditions
Interventions
Trade Name: NP137
Product Name: NP137
Product Code: NP137
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: NP127
Other descriptive name: NP137
Concentration unit: mg/ml milligram(s)/mil
Sponsors
NETRIS PHARMA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: I1. Be women = 18 years at time of inform consent signature. I2. Patient with histologically confirmed locally advanced / metastatic endometrial carcinoma or cervix adenocarcinoma or epidermoid carcinoma. I3. Previously treated by at least one line of chemotherapy, but no more than 3 lines. A minimal wash-out period of 6 months after completion of last chemotherapy with platinum and paclitaxel is required prior to entering the study. I4. For endometrium carcinoma: Mutational profile (MSI/MSS status) available before randomization (see St Paul de Vence 2019- ARCAGY – GINECO Group recommendation) I5. Documented disease progression as per RECIST V1.1 after prior systemic chemotherapy regimen and presence of at least one lesion evaluable for response according to RECIST 1.1 I6. Have provided a representative archival tumor sample in formalin-fixed paraffin embedded (FFPE) block (primary tumor or metastasis) or newly obtained core or excisional biopsy of a tumor lesion toghether with an associated pathology report. I7.Optional for patient having consented to tumour biopsies : Presence of at least one tumor lesion visible by medical imaging and accessible to repeatable percutaneous sampling that permits core needle biopsy without unacceptable risk of a significant procedural complications, and suitable for retrieval of 4 cores using a 16-gauge diameter needle or larger. Note: lesions to be biopsied should not be selected as RECIST target lesions. Bone lesions arare not adequate for biopsies and lymph nodes lesions should not be considered as prime targets for biopsies. I8.Life expectancy = 3 months. I9.Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1. I10. Demonstrate adequate organ function as defined in table page 45 (section 2.3.1 inclusion criteria. all screening laboratory tests should be performed within 7 days prior C1D1) I11. Women of child-bearing potential must have a negative serum pregnancy test at screening (Pregnancy testing (urine) should be within 72 hours of C1D1) and must agree to use 2 effective forms of contraception from the time of the treatment period and of the negative pregnancy test up 120 days after the last dose of IMP (NP137 and/or Pembrolizumab) or 6 months after the last CT study drugs for patient in Arm A (CT only) or if patient discontinue NP137 and/or Pembrolizumab before the end of their CT. I12. Patient should understand, sign, and date the written voluntary informed consent form prior to any protocol-specific procedures. I13. Patient should be able and willing to comply with study visits and procedures as per protocol 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 120 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 120
Exclusion criteria
Exclusion criteria: E1. Persistence of CTCAE = Grade 2 toxicity due to prior anti-cancer therapy (except alopecia (any grades), Grade =1 peripheral neuropathy). E2. History of (=Grade 3) allergic anaphylactic reactions to one of the components of NP137, pembrolizumab, paclitaxel, carboplatin and/or any of their excipients. E3. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment. E4. Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. E5. Prior/concomitant Therapy: - Have received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137) and was discontinued from that treatment due to a Grade =3 irAE - Have received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to treatment, C1D1. - Have received prior radiotherapy within 4 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=2 weeks of radiotherapy) to non-CNS disease. - Have had major surgery within 4 weeks of start of study treatment. Participants must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment, C1D1. - Have received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed. - Have received immunosuppressive medication within 2 weeks with the exceptions of intranasal, topical and inhaled corticosteroids or systemic corticosteroids at doses which are not to exceed 10 mg/day of prednisone, or equivalent doses of another corticosteroid E6. Have a history of autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. - History of autoimmune disease which include but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Safety Run in part: To assess the safety of the proposed therapeutic combinations according to the incidence of DLT. Phase II part: To investigate the clinical activity of the proposed therapeutic combinations as defined by the 3-month objective response rate (ORR-3m) as per RECIST V1.1. ;Secondary Objective: Both Parts : • To further document the safety profile of the proposed therapeutic combinations. • To assess the PK parameters of NP137. • To further assess the anti-tumor activity of the proposed combination (in terms of Best overall response, Duration of response, Clinical Benefit rate at 3 months [CBR-3m], PFS and OS. • Tumor response at 3 months will be also assessed by using iRECIST. • Global Tumour response will be assessed by using V1.1 and iRECIST ;Primary end point(s): => Safety Run in part: All toxicities will be graded using NCI CTCAE Version 5.0 based on the investigator assessment. The DLT window of observation will be during Cycles 1 and 2. The occurrence of any of the following toxicities during Cycles 1 and 2 will be considered a DLT, if assessed by the investigator to be possibly, probably, or definitely related to study treatments administration: 1.Grade 4 hematologic toxicity lasting =7 days, except thrombocytopenia: •Grade 4 thrombocytopenia of any duration •Grade 3 thrombocytopenia associated with clinically significant bleeding 2.Febrile neutropenia Grade 3 or Grade 4 3.Grade 4 non-hematologic toxicity (not laboratory). 4.Any non-hematologic (not laboratory) AE = Grade 3 should be considered a DLT, with the following exceptions: Grade 3 fatigue lasting = 3 days; Grade 3 diarrhea, nausea, or vomiting without use of anti-emetics or anti-diarrheas per standard of care; Grade 3 rash without use of corticosteroids or anti-inflammatory agents per standard of care. 5.Any Grade 3 or Grade 4 non-hematologic laboratory value if: •Clinically significant medical intervention is required to treat the s | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoint - Global Overall response Rate (ORR) as per RECIST V1.1 AND modified criteria for immunotherapies iRECIST (Seymour et al. Lancet Oncol 2017) - Overall response Rate (ORR) after 3 months of treatment will be also assessed as per modified criteria for immunotherapies iRECIST (Seymour et al. Lancet Oncol 2017) - Duration of Response (DoR) - Best Overall Response Rate - Clinical Benefit Rate (CBR) - Progression-free survival (PFS) - Overall survival (OS) Pharmacokinetic endpoints: - The following PK parameters will be determined for NP137 treated patients during the safety run in period only: Cmax, tmax, AUCt, AUC8 , CL, t½. Safety will continue to be assessed by the following assessments all along the Phase II part of this study : adverse events (AEs), vital signs, ECG, physical examination, laboratory safety assessments (hematological and biochemical parameters). All AEs will be graded according to NCI-CTCAE V5.0. In case of Infusion Related Reaction, blood samples will be collected to monitor the PK profile and Immunogenicity using ADA for NP137 assays. ;Timepoint(s) of evaluation of this end point: Duration of Response: from the date of first objective response until the first date of disease progression or subsequent therapy or death . Best Overall Response Rate: from the date of the first study treatment to progression or subsequent therapy or death Progression-free Survival: from first study drug intake until disease progression or subsequent therapy or death Overall Survival: from the first day of study treatment to the date of death. Overall response Rate: 3 months of treatment. Global Overall response Rate from the date of the first study treatment to progression or subsequent therapy. Pharmacokinetics endpoints: Over the first 6 cycles of NP137 patients enrolled druring the Safety run in part Safety: all along the Phase II part in all patients enrolled | — |
Countries
France
Contacts
Public ContactClinical Trial Information
Centre Léon Bérard
Outcome results
None listed