Advanced and early-stage malignancies MedDRA version: 21.0 Level: LLT Classification code 10048683 Term: Advanced cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: FS118
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: None
Current Sponsor code: FS118
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concent
Sponsors
invoX Pharma Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Core Inclusion Criteria: 1.The subject provides written informed consent for the trial. 2.=18 years of age on the day of signing the informed consent. 3.Have an ECOG performance status of 0 to 1. 4.Have a life expectancy of at least 3 months. Cohort A (NSCLC): In addition to the core inclusion criteria, each subject in Cohort A must also meet the following inclusion criteria to be enrolled: 5.Histological or cytological diagnosis of NSCLC. 6.Tumour negative for EGFR mutation and ALK translocation. 7.One prior line of a platinum-doublet regimen that was given for at least 2 cycles and that did not contain a PD-(L)1 or any other health authority approved or experimental immune modulating agent. 8.Have measurable disease per RECIST v1.1. Cohort B (NSCLC WOO): In addition to the core inclusion criteria, each subject in Part B must meet the following inclusion criteria: 9.Histological or cytological diagnosis of NSCLC. 10.Tumour negative for EGFR mutation and ALK translocation. 11.Subjects must have adequate lung function to permit surgical resection. 12.At least 1 measurable lesion as per RECIST v1.1. Cohort C (DLBCL): In addition to the core inclusion criteria, each subject must meet the following inclusion criteria: 13.Histologically confirmed diagnosis of DLBCL with relapsed and/or refractory disease. 14.Received at least two systemic regimens for the treatment of DLBCL. One therapy line must have included a CD20-targeted therapy and one therapy line must have included CAR-T cell therapy where this is the institution´s standard of care, unless contraindicated. 15.At least one bi-dimensionally, PET positive, measurable disease site by spiral CT scan defined as a lesion that measures at least =15 mm in the LD and =10 mm in the SAD at baseline as defined by Lugano classification. For further information, please refer to the clinical 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 64 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: Core Exclusion Criteria Subjects are excluded from the study if any of the following criteria apply: 1.Has 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. 2.Has received prior systemic anti-cancer therapy including investigational agents within 28 days prior to treatment. 3.Has received prior radiotherapy within 2 weeks of start of study treatment. Subjects 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 to non-CNS disease. 4.Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. 5.Has known active CNS metastases and/or carcinomatous meningitis. 6. Has an active autoimmune disease that has required systemic treatment in past 2 years. 7. Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease. 8. Has a history of prior severe or life-threatening infusion related reaction or skin adverse reaction related to previous treatment with other immune stimulatory anticancer agents. Exclusion Criteria Cohort A (NSCLC): 8. Receipt of greater than 1 line of treatment with chemotherapy for Stage IIIB/IIIC/IV disease. 9. Has received radiation therapy to the lung that is >30 Gy within 6 months of the first dose of trial treatment. Exclusion Criteria Cohort B (NSCLC WOO): 10. Administration of chemotherapy or any other anti-cancer therapy (including radiotherapy) in the pre-operative period. Exclusion Criteria Cohort C: DLBCL: 11.Known history of “double or triple hit” genetics or cytogenetic abnormalities involving chromosomal rearrangements of c-MYC, BCL-2 and BCL-6 genes. 12.Subjects that have undergone ASCT within the period =3 months prior to signing the ICF. 13.Subjects that have received an infusion of CAR T cells within 60 days prior to the planned date of dosing with FS118. For further information, please refer to the clinical protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Cohort A (NSCLC ): To assess the efficacy of FS118 in terms of radiological response in all subjects; Cohort B (NSCLC WOO): To evaluate changes in specific T cell density (cells/mm2) in tumour samples collected pre- and post-treatment with FS118. Cohort C (DLBCL): To assess the efficacy of FS118 in terms of radiological response. ;Secondary Objective: Cohort A (NSCLC ): To assess the efficacy of FS118 in all subjects by alternative endpoints; To assess PK parameters for FS118; Assessment of the safety and tolerability of FS118; Cohort B (NSCLC WOO): Assessment of MPR to pre-operative FS118 therapy in resected tumour and lymph nodes; Assessment of radiographic response to pre-operative FS118 therapy; To assess the safety and tolerability of FS118 given in a pre-operative setting; To assess PK parameters for FS118; To evaluate soluble receptors (LAG-3 and PD-L1) following pre-operative FS118 therapy; Cohort C (DLBCL): To assess the efficacy of FS118 in all subjects by alternative endpoints; To assess PK parameters for FS118; Assessment of the safety and tolerability of FS118.;Primary end point(s): Cohort A Efficacy Endpoints: Overall response rate (ORR) as per RECIST v1.1. Cohort B Biomarker/Pharmacodynamic Markers Endopoints: Change in tumour infiltrating T cells subtypes in response to FS118. Cohort C Efficacy Endpoints: ORR as per the Lugano Classification.;Timepoint(s) of evaluation of this end point: Throughout the study duration at the study visits. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Throughout the study duration.;Secondary end point(s): Cohort A Efficacy Endpoints: •Assessments of antitumor activity include DCR, DoR, DoC, and PFS/iPFS as assessed by RECIST v1.1 and iRECIST. •OS. PK Endpoints: •PK endpoints include, but are not limited to the following parameters: Cycle 1: Cmax, Tmax, Ctrough, AUC, T1/2, AUC0- t, Cavg (= AUC0-t/t), CL, Vd, and Rac for AUC0-t. •Cycle 2 onwards: Cmax, Tmax, Ctrough. Safety Endpoints: •Incidence, severity, and duration of AEs as defined by CTCAE v5.0. Cohort B Efficacy Endpoints: •MPR defined as <10% residual viable tumour cells in the resection specimen. •ORR assessed as per RECIST v1.1. Safety Endpoints: •The number of subjects with Grade 2, 3 and 4 laboratory abnormalities, as defined by CTCAE v5.0. •The number of Grade 2, 3 and 4 AEs that occur while a subject is participating in the study, as defined by CTCAE v5.0. PK Endpoints: PK endpoints include, but are not limited to the following parameters: •Cycle 1: Cmax, Tmax, Ctrough, AUC, T1/2, AUC0- t, Cavg (= AUC0-t/t), CL, Vd, and Rac for AUC0-t. Biomarker/Pharmacology/Pharmacodynamic Endpoints: Fold induction of sLAG-3 and sPD-L1. Cohort C Efficacy Endpoints: •Assessments of antitumor activity include DCR, DoR, DoC, and PFS as assessed by the Revised Response Criteria for Malignant Lymphoma. •OS. PK Endpoints: •PK endpoints include, but are not limited to the following parameters: Cycle 1: Cmax, Tmax, Ctrough, AUC, T1/2, AUC0-t, Cavg (= AUC0-t/t), CL, Vd, and Rac for AUC0-t. •Cycle 2 onwards: Cmax, Tmax, Ctrough. Safety Endpoints: Incidence, severity, and duration of AEs as defined by CTCAE v5.0. | — |
Countries
Bulgaria, France, Georgia, India, Moldova, Republic of, Ukraine
Contacts
Public ContactinvoX Pharma Clinical Trials
invoX Pharma Limited
Outcome results
None listed