Metastatic Solid Tumors, Relapsed/Refractory Non-Hodgkin Lymphoma
Conditions
Keywords
Solid Tumors, Non-Hodgkin Lymphoma, NHL, MEN1309, CD205, Relapsed, Refractory, R-R NHL, ADC, Antibody-Drug Coniugate, Metastatic Tumors
Brief summary
The purpose of this clinical trial is to identify the highest dose of MEN1309 drug with acceptable safety profile and that can be used in patients affected by CD205-positive solid tumors and Non-Hodgkin Lymphoma
Detailed description
This clinical trial will investigate the safety and activity of MEN1309 in patients with CD205-positive metastatic solid tumors and Non-Hodgkin Lymphoma who have tried other types of treatment for cancer without adequate response (or the cancer came back). CD205 is a protein present in certain types of cancer. This is a Phase I study, which means that it is designed to look at several dose levels of a study drug in small groups of patients to find the dose that is well-tolerated and suitable to be administered in subsequent clinical trials in patients. The clinical trial is also looking at the effectiveness of the study drug. This is the first time the study drug will be given in humans. The clinical trial consists of two sequential parts: * Part 1 involves patients with CD205-positive metastatic solid tumors and the main purpose of this part of the clinical trial is to determine the highest dose of the study drug that can be used safely in these type of cancers. * Part 2 involves patients with CD205-positive Non-Hodgkin Lymphoma and will test doses of MEN1309 which have demonstrated to be adequately tolerated in patients with solid tumors. Patients participating to the clinical trial will take the study drug as intravenous infusion once every 3 weeks. The clinical trial includes four periods: a pre-screening period (to check if tumor is positive for CD205), a screening period (to check whether the participation to the clinical trial is right for patient), a treatment period (when patient receives the study drug), and a follow-up period (to check the health status of the patient after stopping study treatment).
Interventions
DRUGMEN1309
MEN1309 solution for intravenous infusion once every 3 weeks
Sponsors
Menarini Group
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Cohort1 0.05mg/kg STEP 1 Solid Tumors Cohort2 0.10mg/kg STEP 1 Solid Tumors Cohort3 0.20mg/kg STEP 1 Solid Tumors Cohort4 0.40mg/kg STEP 1 Solid Tumors Cohort5 0.80mg/kg STEP 1 Solid Tumors Cohort6 1.60mg/kg STEP 1 Solid Tumors Cohort7 2.40mg/kg STEP 1 Solid Tumors Cohort8 3.36mg/kg STEP 1 Solid Tumors + GCSF Cohort7b 2.40mg/kg STEP 1 Solid Tumors +GCSF Cohort7c 2.00mg/kg STEP 1 Solid Tumors +GCSF Cohort5 0.80mg/kg STEP 2 NHL
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: 1. Male or female patients aged ≥ 18 years. 2. Patients with: * confirmed diagnosis of advanced or metastatic solid tumor and diagnosis of multiple relapsed or refractory NHL; * progressive after last treatment received; * availability of archived tumor material, either as a block or slides; * measurable or evaluable disease by Response Evaluation Criteria in solid tumors guideline (RECIST v1.1) and by Cheson Criteria (The Lugano Classification, 2014) in NHL. 3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2. 4. Neutrophil count ≥ 1,500/µL; platelets ≥ 100,000/µL; haemoglobin ≥ 9 g/dL. 5. Adequate renal and hepatic laboratory assessments. 6. Life expectancy of at least 2 months. 7. Woman of childbearing potential (WOCBP) who agrees to use highly effective contraception (see Appendix I). Main
Exclusion criteria
1. Central nervous system involvement (excluding treated stable cerebral metastasis, not requiring therapy to control symptoms in the last 60 days). 2. Pregnant or breastfeeding women. 3. Life-threatening illnesses other than solid tumors and NHL, uncontrolled medical conditions or organ system dysfunction which, in the Investigator's opinion, could compromise the patient's safety, or put the study outcomes at risk. 4. Less than 2 previous cancer treatments, including high dose chemotherapy and ASCT, for NHL unless patient refuses standard therapy and/or is not eligible for ASCT. 5. Have significant, uncontrolled, or active cardiovascular disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum-Tolerated Dose (MTD) | 21-day period after the first dose | Defined as the highest dose level at which no more than 1 of 6 patients experiences a DLT during the DLT assessment window. |
| Dose-Limiting Toxicity (DLT) | 21-day period after the first dose | Adverse drug reactions (ADRs) that will be assessed during Cycle 1: * any grade ≥ 3 cardiac toxicity, new segmental wall-motion abnormalities, or cardiac troponin I or T elevation of grade 3 or higher; * any grade ≥ 3 elevations in total bilirubin, hepatic transaminases, or ALP levels; in patients with baseline grade 2 hepatic transaminase or ALP levels, an elevation to ≥ 10 x ULN is considered a DLT; * any grade 3 non-haematologic toxicity lasting \> 7 days, (excluding diarrhea/nausea for which no adequate and optimal therapy has been implemented and alopecia); * any grade 3 vomiting lasting \> 3 days despite adequate and optimal therapy; * any grade ≥ 4 non-haematologic toxicity; * any grade 4 thrombocytopenia or anemia; * any grade 4 neutropenia lasting \> 7 days or febrile neutropenia; * any treatment delay of \> 2 weeks because of delayed recovery from toxicity related to MEN1309 (except for alopecia). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | Through study completion, from August 28, 2017 to January 8, 2020 (2 years and 4 months) | The Number of days between the first study administration to the date of first documented disease progression. |
| Preliminary Tumor Activity (RR) | From Day1Visit1 to End of the treatment (At Baseline no more than 6 weeks before treatment and then every cycle starting from cycle 3 until End of Study) | Preliminary tumor activity (RR) Response Rate. RECIST v 1.1 assessment was performed using CT or MRI scan of the chest and abdomen (including adrenal glands). For the baseline assessment, CT or MRI scan were to be performed no more than 6 weeks (4+2 weeks) before the treatment start. Follow-up assessment were performed every other cycle starting from cycle 3 until the End of Study Visit. |
| Preliminary Antitumor Activity (DCR) | From Day1Visit1 to End of the treatment (At Baseline no more than 6 weeks before treatment and then every cycle starting from cycle 3 until End of Study) | Preliminary Antitumor Activity (DCR) Disease control Rate. RECIST v 1.1 assessment was performed using CT or MRI scan of the chest and abdomen (including adrenal glands). For the baseline assessment, CT or MRI scan were to be performed no more than 6 weeks (4+2 weeks) before the treatment start. Follow-up assessment were performed every other cycle starting from cycle 3 until the End of Study Visit. |
| Preliminary Antitumor Activity (DOR) | From Day1Visit1 to End of the treatment (At Baseline no more than 6 weeks before treatment and then every cycle starting from cycle 3 until End of Study) | Prliminary Antitumor Activity. Measure of the Duration of response. RECIST v 1.1 assessment was performed using CT or MRI scan of the chest and abdomen (including adrenal glands). For the baseline assessment, CT or MRI scan were to be performed no more than 6 weeks (4+2 weeks) before the treatment start. Follow-up assessment were performed every other cycle starting from cycle 3 until the End of Study Visit. |
| MEN1309 PK Parameter Ctrough | Pre-infusion Cycle 2 | MEN1309 PK parameter Ctrough (Predose concentration) |
| MEN1309 Pharmacokinetic (PK) Parameter t1/2 | Cycle 1 | MEN1309 Pharmacokinetic (PK) parameter t1/2 (terminal serum half-life) |
| MEN1309 Pharmacokinetic (PK) Parameter AUC | Cycle 1 | MEN1309 Pharmacokinetic (PK) parameter AUC (area under curve) |
| MEN1309 (PK) Parameter CL | Cycle 1 | Systemic clearance of MEN1309 Pharmacokinetic |
| MEN1309 Pharmacokinetic (PK) Parameter Vd | Cycle 1 | volume of distribution based on the terminal phase |
| MEN1309 PK Parameter Cmax | Cycle 1 | Cmax is the maximum drug concentration |
| Overall Survival | Through study completion, from August 28, 2017 to January 8, 2020 (2 years and 4 months) | Timeframe between the first study drug administration and death from any cause. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Correlation of CD205 Expression in Tumors With Clinical Activity of MEN1309 Assessed According to RECIST 1.1 or Cheson Criteria (2014) | Through study completion, from August 28, 2017 to January 8, 2020 (2 years and 4 months) | Exploratory Endpoint: Correlation of CD205 expression in tumors with clinical activity of MEN1309 assessed according to RECIST 1.1 or Cheson Criteria (2014) in terms of Response Rate, Disease control rate, duration of response, overall survival, and progression free survival. N.B: No Data were available to assess this outcome. |
| Incidence of Anti-MEN1309 Antibodies | Day 1 of each Cycle (each cycle is 21 days) | Exploratory Endpoint: Immunogenicity analysis regarding the Incidence of anti-MEN1309 antibodies. |
Countries
Belgium, Italy, Spain, United Kingdom
Participant flow
Recruitment details
It was planned to perform this study in 7 sites across 4 European countries: Spain, Italy, Belgium, and UK. Patients were only recruited in 5 sites (3 ES, 1 IT1, 1 BE) prior to the study being stopped. The study started in date 28 August 2017 (FPI) to 19 November 2019 (LPLV). Study Termination letter was sent to authorities on 08 January 2020.
Pre-assignment details
Male or female patients aged ≥ 18 years. For Step 1 of the study, patients with diagnosis of advanced or metastatic solid tumor. For Step 2, patients with histologically confirmed diagnosis of relapsed or refractory NHL. In both Steps the tumor need to have a positivity (≥ 1+ IHC staining) for CD205.
Participants by arm
| Arm | Count |
|---|---|
| Cohort1 0.05mg/kg STEP 1 Solid Tumors Patients with CD205-positive advanced solid tumors, who recieved 0.05mg/kg of MEN1309. | 1 |
| Cohort2 0.10mg/kg STEP 1 Solid Tumors Patients with CD205-positive advanced solid tumors, who recieved 0.10mg/kg of MEN1309. | 1 |
| Cohort3 0.20mg/kg STEP 1 Solid Tumors Patients with CD205-positive advanced solid tumors, who recieved 0.20mg/kg of MEN1309. | 1 |
| Cohort4 0.40mg/kg STEP 1 Solid Tumors Patients with CD205-positive advanced solid tumors, who recieved 0.40mg/kg of MEN1309. | 1 |
| Cohort5 0.80mg/kg STEP 1 Solid Tumors Patients with CD205-positive advanced solid tumors, who recieved 0.80mg/kg of MEN1309. | 1 |
| Cohort6 1.60mg/kg STEP 1 Solid Tumors Patients with CD205-positive advanced solid tumors, who recieved 1.60mg/kg of MEN1309. | 6 |
| Cohort7 2.40mg/kg STEP 1 Solid Tumors Patients with CD205-positive advanced solid tumors, who recieved 2.40mg/kg of MEN1309. | 6 |
| Cohort8 3.36mg/kg STEP 1 Solid Tumors + GCSF Patients with CD205-positive advanced solid tumors, who recieved 3.36mg/kg of MEN1309. | 3 |
| Cohort7b 2.40mg/kg STEP 1 Solid Tumors +GCSF Patients with CD205-positive advanced solid tumors, who recieved 2.40mg/kg of MEN1309. | 3 |
| Cohort7c 2.00mg/kg STEP 1 Solid Tumors +GCSF Patients with CD205-positive advanced solid tumors, who recieved 2.00mg/kg of MEN1309. | 4 |
| Cohort5 0.80mg/kg STEP 2 NHL Patients with CD205-positive multiple relapsed or refractory Non Hodking Lymphoma, who recieved 0.80mg/kg of MEN1309. | 1 |
| Total | 28 |
Baseline characteristics
| Characteristic | Cohort2 0.10mg/kg STEP 1 Solid Tumors | Cohort3 0.20mg/kg STEP 1 Solid Tumors | Cohort4 0.40mg/kg STEP 1 Solid Tumors | Cohort5 0.80mg/kg STEP 1 Solid Tumors | Cohort6 1.60mg/kg STEP 1 Solid Tumors | Cohort1 0.05mg/kg STEP 1 Solid Tumors | Cohort7 2.40mg/kg STEP 1 Solid Tumors | Cohort8 3.36mg/kg STEP 1 Solid Tumors + GCSF | Cohort7b 2.40mg/kg STEP 1 Solid Tumors +GCSF | Cohort7c 2.00mg/kg STEP 1 Solid Tumors +GCSF | Cohort5 0.80mg/kg STEP 2 NHL | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 4 Participants | 1 Participants | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 0 Participants | 18 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Black African American | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 1 participants | 1 participants | 1 participants | 1 participants | 6 participants | 1 participants | 6 participants | 3 participants | 2 participants | 3 participants | 1 participants | 26 participants |
| Race/Ethnicity, Customized Other | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized White | 1 participants | 1 participants | 1 participants | 1 participants | 6 participants | 1 participants | 6 participants | 3 participants | 3 participants | 4 participants | 1 participants | 28 participants |
| Region of Enrollment Belgium | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants | 0 participants | 1 participants | 1 participants | 1 participants | 0 participants | 0 participants | 5 participants |
| Region of Enrollment Italy | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants | 0 participants | 2 participants |
| Region of Enrollment Spain | 1 participants | 1 participants | 1 participants | 0 participants | 5 participants | 1 participants | 5 participants | 2 participants | 2 participants | 3 participants | 1 participants | 0 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants | 1 Participants | 6 Participants | 3 Participants | 1 Participants | 2 Participants | 0 Participants | 19 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 1 Participants | 9 Participants |
| Weight | 56.80 Kg STANDARD_DEVIATION 0 | 60.60 Kg STANDARD_DEVIATION 0 | 62.50 Kg STANDARD_DEVIATION 0 | 53.50 Kg STANDARD_DEVIATION 0 | 64.27 Kg STANDARD_DEVIATION 17.382 | 66.10 Kg STANDARD_DEVIATION 0 | 67.30 Kg STANDARD_DEVIATION 15.725 | 61.17 Kg STANDARD_DEVIATION 8.52 | 76.57 Kg STANDARD_DEVIATION 15.584 | 64.55 Kg STANDARD_DEVIATION 8.805 | 109.4 Kg STANDARD_DEVIATION 0 | 66.68 Kg STANDARD_DEVIATION 12.886 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 1 / 1 | 1 / 1 | 1 / 1 | 1 / 1 | 1 / 6 | 5 / 6 | 1 / 3 | 0 / 3 | 3 / 4 | 0 / 1 |
| other Total, other adverse events | 1 / 1 | 0 / 1 | 1 / 1 | 1 / 1 | 1 / 1 | 6 / 6 | 6 / 6 | 3 / 3 | 3 / 3 | 4 / 4 | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 | 1 / 1 | 0 / 1 | 1 / 1 | 0 / 1 | 5 / 6 | 5 / 6 | 3 / 3 | 3 / 3 | 2 / 4 | 1 / 1 |
Outcome results
Primary
Dose-Limiting Toxicity (DLT)
Adverse drug reactions (ADRs) that will be assessed during Cycle 1: * any grade ≥ 3 cardiac toxicity, new segmental wall-motion abnormalities, or cardiac troponin I or T elevation of grade 3 or higher; * any grade ≥ 3 elevations in total bilirubin, hepatic transaminases, or ALP levels; in patients with baseline grade 2 hepatic transaminase or ALP levels, an elevation to ≥ 10 x ULN is considered a DLT; * any grade 3 non-haematologic toxicity lasting \> 7 days, (excluding diarrhea/nausea for which no adequate and optimal therapy has been implemented and alopecia); * any grade 3 vomiting lasting \> 3 days despite adequate and optimal therapy; * any grade ≥ 4 non-haematologic toxicity; * any grade 4 thrombocytopenia or anemia; * any grade 4 neutropenia lasting \> 7 days or febrile neutropenia; * any treatment delay of \> 2 weeks because of delayed recovery from toxicity related to MEN1309 (except for alopecia).
Time frame: 21-day period after the first dose
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Doses STEP 1-Solid Tumors | Dose-Limiting Toxicity (DLT) | 0 Dose Limiting Toxicities |
| Cohort2 0.10mg/kg STEP 1 Solid Tumors | Dose-Limiting Toxicity (DLT) | 0 Dose Limiting Toxicities |
| Cohort3 0.20mg/kg STEP 1 Solid Tumors | Dose-Limiting Toxicity (DLT) | 0 Dose Limiting Toxicities |
| Cohort4 0.40mg/kg STEP 1 Solid Tumors | Dose-Limiting Toxicity (DLT) | 0 Dose Limiting Toxicities |
| Cohort5 0.80mg/kg STEP 1 Solid Tumors | Dose-Limiting Toxicity (DLT) | 0 Dose Limiting Toxicities |
| Cohort6 1.60mg/kg STEP 1 Solid Tumors | Dose-Limiting Toxicity (DLT) | 1 Dose Limiting Toxicities |
| Cohort7 2.40mg/kg STEP 1 Solid Tumors | Dose-Limiting Toxicity (DLT) | 1 Dose Limiting Toxicities |
| Cohort8 3.36mg/kg STEP 1 Solid Tumors + GCSF | Dose-Limiting Toxicity (DLT) | 2 Dose Limiting Toxicities |
| Cohort7b 2.40mg/kg STEP 1 Solid Tumors +GCSF | Dose-Limiting Toxicity (DLT) | 3 Dose Limiting Toxicities |
| Cohort7c 2.00mg/kg STEP 1 Solid Tumors +GCSF | Dose-Limiting Toxicity (DLT) | 2 Dose Limiting Toxicities |
| Cohort5 0.80mg/kg STEP 2 NHL | Dose-Limiting Toxicity (DLT) | 0 Dose Limiting Toxicities |
Primary
Maximum-Tolerated Dose (MTD)
Defined as the highest dose level at which no more than 1 of 6 patients experiences a DLT during the DLT assessment window.
Time frame: 21-day period after the first dose
Population: MTD was evaluated only in the STEP 1 since in STEP 2 only one patient was treated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Doses STEP 1-Solid Tumors | Maximum-Tolerated Dose (MTD) | 1.6 mg/Kg |
Secondary
MEN1309 Pharmacokinetic (PK) Parameter AUC
MEN1309 Pharmacokinetic (PK) parameter AUC (area under curve)
Time frame: Cycle 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Doses STEP 1-Solid Tumors | MEN1309 Pharmacokinetic (PK) Parameter AUC | 3.94 hr * microgram/mL | Standard Deviation 0 |
| Cohort2 0.10mg/kg STEP 1 Solid Tumors | MEN1309 Pharmacokinetic (PK) Parameter AUC | 3.78 hr * microgram/mL | Standard Deviation 0 |
| Cohort3 0.20mg/kg STEP 1 Solid Tumors | MEN1309 Pharmacokinetic (PK) Parameter AUC | 6.16 hr * microgram/mL | Standard Deviation 0 |
| Cohort4 0.40mg/kg STEP 1 Solid Tumors | MEN1309 Pharmacokinetic (PK) Parameter AUC | 11.86 hr * microgram/mL | Standard Deviation 0 |
| Cohort5 0.80mg/kg STEP 1 Solid Tumors | MEN1309 Pharmacokinetic (PK) Parameter AUC | 57.49 hr * microgram/mL | Standard Deviation 0 |
| Cohort6 1.60mg/kg STEP 1 Solid Tumors | MEN1309 Pharmacokinetic (PK) Parameter AUC | 583.38 hr * microgram/mL | Standard Deviation 213.45 |
| Cohort7 2.40mg/kg STEP 1 Solid Tumors | MEN1309 Pharmacokinetic (PK) Parameter AUC | 1038.12 hr * microgram/mL | Standard Deviation 257.12 |
| Cohort8 3.36mg/kg STEP 1 Solid Tumors + GCSF | MEN1309 Pharmacokinetic (PK) Parameter AUC | 2045.41 hr * microgram/mL | Standard Deviation 1130.69 |
| Cohort7b 2.40mg/kg STEP 1 Solid Tumors +GCSF | MEN1309 Pharmacokinetic (PK) Parameter AUC | 958.94 hr * microgram/mL | Standard Deviation 417.06 |
| Cohort7c 2.00mg/kg STEP 1 Solid Tumors +GCSF | MEN1309 Pharmacokinetic (PK) Parameter AUC | 689.33 hr * microgram/mL | Standard Deviation 295.5 |
| Cohort5 0.80mg/kg STEP 2 NHL | MEN1309 Pharmacokinetic (PK) Parameter AUC | 111.44 hr * microgram/mL | Standard Deviation 0 |
Secondary
MEN1309 Pharmacokinetic (PK) Parameter t1/2
MEN1309 Pharmacokinetic (PK) parameter t1/2 (terminal serum half-life)
Time frame: Cycle 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Doses STEP 1-Solid Tumors | MEN1309 Pharmacokinetic (PK) Parameter t1/2 | 2.66 hr | Standard Deviation 0 |
| Cohort2 0.10mg/kg STEP 1 Solid Tumors | MEN1309 Pharmacokinetic (PK) Parameter t1/2 | 3.17 hr | Standard Deviation 0 |
| Cohort3 0.20mg/kg STEP 1 Solid Tumors | MEN1309 Pharmacokinetic (PK) Parameter t1/2 | 2.38 hr | Standard Deviation 0 |
| Cohort4 0.40mg/kg STEP 1 Solid Tumors | MEN1309 Pharmacokinetic (PK) Parameter t1/2 | 16.65 hr | Standard Deviation 0 |
| Cohort5 0.80mg/kg STEP 1 Solid Tumors | MEN1309 Pharmacokinetic (PK) Parameter t1/2 | 93.90 hr | Standard Deviation 0 |
| Cohort6 1.60mg/kg STEP 1 Solid Tumors | MEN1309 Pharmacokinetic (PK) Parameter t1/2 | 18.24 hr | Standard Deviation 6.49 |
| Cohort7 2.40mg/kg STEP 1 Solid Tumors | MEN1309 Pharmacokinetic (PK) Parameter t1/2 | 16.89 hr | Standard Deviation 1.67 |
| Cohort8 3.36mg/kg STEP 1 Solid Tumors + GCSF | MEN1309 Pharmacokinetic (PK) Parameter t1/2 | 27.74 hr | Standard Deviation 2.36 |
| Cohort7b 2.40mg/kg STEP 1 Solid Tumors +GCSF | MEN1309 Pharmacokinetic (PK) Parameter t1/2 | 15.36 hr | Standard Deviation 0.96 |
| Cohort7c 2.00mg/kg STEP 1 Solid Tumors +GCSF | MEN1309 Pharmacokinetic (PK) Parameter t1/2 | 17.24 hr | Standard Deviation 1.24 |
| Cohort5 0.80mg/kg STEP 2 NHL | MEN1309 Pharmacokinetic (PK) Parameter t1/2 | 15.08 hr | Standard Deviation 0 |
Secondary
MEN1309 Pharmacokinetic (PK) Parameter Vd
volume of distribution based on the terminal phase
Time frame: Cycle 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Doses STEP 1-Solid Tumors | MEN1309 Pharmacokinetic (PK) Parameter Vd | 3.14 L | Standard Deviation 0 |
| Cohort2 0.10mg/kg STEP 1 Solid Tumors | MEN1309 Pharmacokinetic (PK) Parameter Vd | 6.69 L | Standard Deviation 0 |
| Cohort3 0.20mg/kg STEP 1 Solid Tumors | MEN1309 Pharmacokinetic (PK) Parameter Vd | 6.73 L | Standard Deviation 0 |
| Cohort4 0.40mg/kg STEP 1 Solid Tumors | MEN1309 Pharmacokinetic (PK) Parameter Vd | 49.47 L | Standard Deviation 0 |
| Cohort5 0.80mg/kg STEP 1 Solid Tumors | MEN1309 Pharmacokinetic (PK) Parameter Vd | 95.45 L | Standard Deviation 0 |
| Cohort6 1.60mg/kg STEP 1 Solid Tumors | MEN1309 Pharmacokinetic (PK) Parameter Vd | 4.97 L | Standard Deviation 2.5 |
| Cohort7 2.40mg/kg STEP 1 Solid Tumors | MEN1309 Pharmacokinetic (PK) Parameter Vd | 4.02 L | Standard Deviation 1.32 |
| Cohort8 3.36mg/kg STEP 1 Solid Tumors + GCSF | MEN1309 Pharmacokinetic (PK) Parameter Vd | 4.73 L | Standard Deviation 1.8 |
| Cohort7b 2.40mg/kg STEP 1 Solid Tumors +GCSF | MEN1309 Pharmacokinetic (PK) Parameter Vd | 5.55 L | Standard Deviation 3.24 |
| Cohort7c 2.00mg/kg STEP 1 Solid Tumors +GCSF | MEN1309 Pharmacokinetic (PK) Parameter Vd | 5.08 L | Standard Deviation 3.08 |
| Cohort5 0.80mg/kg STEP 2 NHL | MEN1309 Pharmacokinetic (PK) Parameter Vd | 16.94 L | Standard Deviation 0 |
Secondary
MEN1309 (PK) Parameter CL
Systemic clearance of MEN1309 Pharmacokinetic
Time frame: Cycle 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Doses STEP 1-Solid Tumors | MEN1309 (PK) Parameter CL | 0.82 L/hr | Standard Deviation 0 |
| Cohort2 0.10mg/kg STEP 1 Solid Tumors | MEN1309 (PK) Parameter CL | 1.46 L/hr | Standard Deviation 0 |
| Cohort3 0.20mg/kg STEP 1 Solid Tumors | MEN1309 (PK) Parameter CL | 1.96 L/hr | Standard Deviation 0 |
| Cohort4 0.40mg/kg STEP 1 Solid Tumors | MEN1309 (PK) Parameter CL | 2.06 L/hr | Standard Deviation 0 |
| Cohort5 0.80mg/kg STEP 1 Solid Tumors | MEN1309 (PK) Parameter CL | 0.70 L/hr | Standard Deviation 0 |
| Cohort6 1.60mg/kg STEP 1 Solid Tumors | MEN1309 (PK) Parameter CL | 0.20 L/hr | Standard Deviation 0.09 |
| Cohort7 2.40mg/kg STEP 1 Solid Tumors | MEN1309 (PK) Parameter CL | 0.17 L/hr | Standard Deviation 0.08 |
| Cohort8 3.36mg/kg STEP 1 Solid Tumors + GCSF | MEN1309 (PK) Parameter CL | 0.13 L/hr | Standard Deviation 0.9 |
| Cohort7b 2.40mg/kg STEP 1 Solid Tumors +GCSF | MEN1309 (PK) Parameter CL | 0.21 L/hr | Standard Deviation 0.07 |
| Cohort7c 2.00mg/kg STEP 1 Solid Tumors +GCSF | MEN1309 (PK) Parameter CL | 0.22 L/hr | Standard Deviation 0.11 |
| Cohort5 0.80mg/kg STEP 2 NHL | MEN1309 (PK) Parameter CL | 0.78 L/hr | Standard Deviation 0 |
Secondary
MEN1309 PK Parameter Cmax
Cmax is the maximum drug concentration
Time frame: Cycle 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Doses STEP 1-Solid Tumors | MEN1309 PK Parameter Cmax | 0.73 microgram/mL | Standard Deviation 0.19 |
| Cohort2 0.10mg/kg STEP 1 Solid Tumors | MEN1309 PK Parameter Cmax | 0.87 microgram/mL | Standard Deviation 0.16 |
| Cohort3 0.20mg/kg STEP 1 Solid Tumors | MEN1309 PK Parameter Cmax | 1.75 microgram/mL | Standard Deviation 0.09 |
| Cohort4 0.40mg/kg STEP 1 Solid Tumors | MEN1309 PK Parameter Cmax | 3.16 microgram/mL | Standard Deviation 0 |
| Cohort5 0.80mg/kg STEP 1 Solid Tumors | MEN1309 PK Parameter Cmax | 9.67 microgram/mL | Standard Deviation 2.03 |
| Cohort6 1.60mg/kg STEP 1 Solid Tumors | MEN1309 PK Parameter Cmax | 31.87 microgram/mL | Standard Deviation 9.11 |
| Cohort7 2.40mg/kg STEP 1 Solid Tumors | MEN1309 PK Parameter Cmax | 43.94 microgram/mL | Standard Deviation 11.25 |
| Cohort8 3.36mg/kg STEP 1 Solid Tumors + GCSF | MEN1309 PK Parameter Cmax | 64.97 microgram/mL | Standard Deviation 33.4 |
| Cohort7b 2.40mg/kg STEP 1 Solid Tumors +GCSF | MEN1309 PK Parameter Cmax | 44.50 microgram/mL | Standard Deviation 15.79 |
| Cohort7c 2.00mg/kg STEP 1 Solid Tumors +GCSF | MEN1309 PK Parameter Cmax | 33.52 microgram/mL | Standard Deviation 9.29 |
| Cohort5 0.80mg/kg STEP 2 NHL | MEN1309 PK Parameter Cmax | 11.36 microgram/mL | Standard Deviation 0 |
Secondary
MEN1309 PK Parameter Ctrough
MEN1309 PK parameter Ctrough (Predose concentration)
Time frame: Pre-infusion Cycle 2
Population: For Cohort 4 the treatment ended at Cycle 1 for the only subejct.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Doses STEP 1-Solid Tumors | MEN1309 PK Parameter Ctrough | 0 ng/mL | Standard Deviation 0 |
| Cohort2 0.10mg/kg STEP 1 Solid Tumors | MEN1309 PK Parameter Ctrough | 0 ng/mL | Standard Deviation 0 |
| Cohort3 0.20mg/kg STEP 1 Solid Tumors | MEN1309 PK Parameter Ctrough | 0 ng/mL | Standard Deviation 0 |
| Cohort5 0.80mg/kg STEP 1 Solid Tumors | MEN1309 PK Parameter Ctrough | 0 ng/mL | Standard Deviation 0 |
| Cohort6 1.60mg/kg STEP 1 Solid Tumors | MEN1309 PK Parameter Ctrough | 0 ng/mL | Standard Deviation 0 |
| Cohort7 2.40mg/kg STEP 1 Solid Tumors | MEN1309 PK Parameter Ctrough | 0 ng/mL | Standard Deviation 0 |
| Cohort8 3.36mg/kg STEP 1 Solid Tumors + GCSF | MEN1309 PK Parameter Ctrough | 0 ng/mL | Standard Deviation 0 |
| Cohort7b 2.40mg/kg STEP 1 Solid Tumors +GCSF | MEN1309 PK Parameter Ctrough | 0 ng/mL | Standard Deviation 0 |
| Cohort7c 2.00mg/kg STEP 1 Solid Tumors +GCSF | MEN1309 PK Parameter Ctrough | 0 ng/mL | Standard Deviation 0 |
| Cohort5 0.80mg/kg STEP 2 NHL | MEN1309 PK Parameter Ctrough | 0 ng/mL | Standard Deviation 0 |
Secondary
Overall Survival
Timeframe between the first study drug administration and death from any cause.
Time frame: Through study completion, from August 28, 2017 to January 8, 2020 (2 years and 4 months)
Population: For Cohorts reported as 0 analyzed the patients were censored (Event Date Not available)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort2 0.10mg/kg STEP 1 Solid Tumors | Overall Survival | 379 Days | Standard Deviation 0 |
| Cohort3 0.20mg/kg STEP 1 Solid Tumors | Overall Survival | 700 Days | Standard Deviation 0 |
| Cohort5 0.80mg/kg STEP 1 Solid Tumors | Overall Survival | 74 Days | Standard Deviation 0 |
| Cohort6 1.60mg/kg STEP 1 Solid Tumors | Overall Survival | 154 Days | Standard Deviation 0 |
| Cohort7 2.40mg/kg STEP 1 Solid Tumors | Overall Survival | 297.75 Days | Standard Deviation 208.73 |
| Cohort7c 2.00mg/kg STEP 1 Solid Tumors +GCSF | Overall Survival | 90.33 Days | Standard Deviation 12.66 |
Secondary
Preliminary Antitumor Activity (DCR)
Preliminary Antitumor Activity (DCR) Disease control Rate. RECIST v 1.1 assessment was performed using CT or MRI scan of the chest and abdomen (including adrenal glands). For the baseline assessment, CT or MRI scan were to be performed no more than 6 weeks (4+2 weeks) before the treatment start. Follow-up assessment were performed every other cycle starting from cycle 3 until the End of Study Visit.
Time frame: From Day1Visit1 to End of the treatment (At Baseline no more than 6 weeks before treatment and then every cycle starting from cycle 3 until End of Study)
Population: Efficacy Population:All eligible patients who receive at least 2 complete treatment cycles and have at least 1 disease assessment are to be considered evaluable for efficacy.~Out of 11 evaluable patients, 11 patients had stable disease (SD), no complete response or partial response was observed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Doses STEP 1-Solid Tumors | Preliminary Antitumor Activity (DCR) | 0 N. of Stable Disease/N. of Pts |
| Cohort2 0.10mg/kg STEP 1 Solid Tumors | Preliminary Antitumor Activity (DCR) | 0 N. of Stable Disease/N. of Pts |
| Cohort3 0.20mg/kg STEP 1 Solid Tumors | Preliminary Antitumor Activity (DCR) | 0 N. of Stable Disease/N. of Pts |
| Cohort5 0.80mg/kg STEP 1 Solid Tumors | Preliminary Antitumor Activity (DCR) | 1 N. of Stable Disease/N. of Pts |
| Cohort7 2.40mg/kg STEP 1 Solid Tumors | Preliminary Antitumor Activity (DCR) | 0.33 N. of Stable Disease/N. of Pts |
| Cohort8 3.36mg/kg STEP 1 Solid Tumors + GCSF | Preliminary Antitumor Activity (DCR) | 0.8 N. of Stable Disease/N. of Pts |
| Cohort7c 2.00mg/kg STEP 1 Solid Tumors +GCSF | Preliminary Antitumor Activity (DCR) | 0 N. of Stable Disease/N. of Pts |
| Cohort5 0.80mg/kg STEP 2 NHL | Preliminary Antitumor Activity (DCR) | 0.25 N. of Stable Disease/N. of Pts |
Secondary
Preliminary Antitumor Activity (DOR)
Prliminary Antitumor Activity. Measure of the Duration of response. RECIST v 1.1 assessment was performed using CT or MRI scan of the chest and abdomen (including adrenal glands). For the baseline assessment, CT or MRI scan were to be performed no more than 6 weeks (4+2 weeks) before the treatment start. Follow-up assessment were performed every other cycle starting from cycle 3 until the End of Study Visit.
Time frame: From Day1Visit1 to End of the treatment (At Baseline no more than 6 weeks before treatment and then every cycle starting from cycle 3 until End of Study)
Population: Data Cannot be reported since it was not analyzed. No Patients had Complete response and Partial Response.
Secondary
Preliminary Tumor Activity (RR)
Preliminary tumor activity (RR) Response Rate. RECIST v 1.1 assessment was performed using CT or MRI scan of the chest and abdomen (including adrenal glands). For the baseline assessment, CT or MRI scan were to be performed no more than 6 weeks (4+2 weeks) before the treatment start. Follow-up assessment were performed every other cycle starting from cycle 3 until the End of Study Visit.
Time frame: From Day1Visit1 to End of the treatment (At Baseline no more than 6 weeks before treatment and then every cycle starting from cycle 3 until End of Study)
Population: Efficacy Population:All eligible patients who receive at least 2 complete treatment cycles and have at least 1 disease assessment are to be considered evaluable for efficacy.~The percentage of patient is 0% since no patient had Complete response or partial response.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Doses STEP 1-Solid Tumors | Preliminary Tumor Activity (RR) | 0 Participants |
| Cohort2 0.10mg/kg STEP 1 Solid Tumors | Preliminary Tumor Activity (RR) | 0 Participants |
| Cohort3 0.20mg/kg STEP 1 Solid Tumors | Preliminary Tumor Activity (RR) | 0 Participants |
| Cohort4 0.40mg/kg STEP 1 Solid Tumors | Preliminary Tumor Activity (RR) | 0 Participants |
| Cohort5 0.80mg/kg STEP 1 Solid Tumors | Preliminary Tumor Activity (RR) | 0 Participants |
| Cohort6 1.60mg/kg STEP 1 Solid Tumors | Preliminary Tumor Activity (RR) | 0 Participants |
| Cohort7 2.40mg/kg STEP 1 Solid Tumors | Preliminary Tumor Activity (RR) | 0 Participants |
| Cohort8 3.36mg/kg STEP 1 Solid Tumors + GCSF | Preliminary Tumor Activity (RR) | 0 Participants |
| Cohort7b 2.40mg/kg STEP 1 Solid Tumors +GCSF | Preliminary Tumor Activity (RR) | 0 Participants |
| Cohort7c 2.00mg/kg STEP 1 Solid Tumors +GCSF | Preliminary Tumor Activity (RR) | 0 Participants |
| Cohort5 0.80mg/kg STEP 2 NHL | Preliminary Tumor Activity (RR) | 0 Participants |
Secondary
Progression Free Survival
The Number of days between the first study administration to the date of first documented disease progression.
Time frame: Through study completion, from August 28, 2017 to January 8, 2020 (2 years and 4 months)
Population: For Cohorts reported as 0 analyzed the patients were censored (Event Date Not available)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort3 0.20mg/kg STEP 1 Solid Tumors | Progression Free Survival | 41 Days | Standard Deviation 0 |
| Cohort5 0.80mg/kg STEP 1 Solid Tumors | Progression Free Survival | 38 Days | Standard Deviation 0 |
| Cohort6 1.60mg/kg STEP 1 Solid Tumors | Progression Free Survival | 36.5 Days | Standard Deviation 0.71 |
| Cohort7 2.40mg/kg STEP 1 Solid Tumors | Progression Free Survival | 155.5 Days | Standard Deviation 190.51 |
| Cohort7b 2.40mg/kg STEP 1 Solid Tumors +GCSF | Progression Free Survival | 100.5 Days | Standard Deviation 28.99 |
| Cohort7c 2.00mg/kg STEP 1 Solid Tumors +GCSF | Progression Free Survival | 37 Days | Standard Deviation 1.73 |
Other Pre-specified
Correlation of CD205 Expression in Tumors With Clinical Activity of MEN1309 Assessed According to RECIST 1.1 or Cheson Criteria (2014)
Exploratory Endpoint: Correlation of CD205 expression in tumors with clinical activity of MEN1309 assessed according to RECIST 1.1 or Cheson Criteria (2014) in terms of Response Rate, Disease control rate, duration of response, overall survival, and progression free survival. N.B: No Data were available to assess this outcome.
Time frame: Through study completion, from August 28, 2017 to January 8, 2020 (2 years and 4 months)
Population: N.B: No Data were available to assess this outcome.
Other Pre-specified
Incidence of Anti-MEN1309 Antibodies
Exploratory Endpoint: Immunogenicity analysis regarding the Incidence of anti-MEN1309 antibodies.
Time frame: Day 1 of each Cycle (each cycle is 21 days)
Population: For this Outcome Results are not available per Cohorts, but only on the total of patients analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Doses STEP 1-Solid Tumors | Incidence of Anti-MEN1309 Antibodies | ADA Positive | 10 Patients |
| All Doses STEP 1-Solid Tumors | Incidence of Anti-MEN1309 Antibodies | ADA Negative | 18 Patients |