Clinical trial NCT03403725: MEN1309 I.v. Infusion in Pts With CD205-positive Metastatic Solid Tumors and Relapsed or Refractory NHL Ph I Study
Official title: Open-Label, Multicenter, Phase I Dose Escalation Study of MEN1309, a CD205 Antibody-Drug Conjugate,in Patients With CD205-Positive Metastatic Solid Tumors and Non-Hodgkin Lymphoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Metastatic Solid Tumors
Relapsed/Refractory Non-Hodgkin Lymphoma
Keywords: Solid Tumors
Non-Hodgkin Lymphoma
NHL
MEN1309
CD205
Relapsed
Refractory
R-R NHL
ADC
Antibody-Drug Coniugate
Metastatic Tumors
Lead sponsor: Menarini Group
Sponsor class: INDUSTRY
First posted: 2018-01-19
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
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
Primary purpose: TREATMENT

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).

Eligibility 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.

Primary outcomes:
measure: Maximum-Tolerated Dose (MTD)
timeFrame: 21-day period after the first dose
measure: Dose-Limiting Toxicity (DLT)
timeFrame: 21-day period after the first dose
Secondary outcomes:
measure: Overall Survival
timeFrame: Through study completion, from "August 28, 2017" to "January 8, 2020" (2 years and 4 months)
measure: Progression Free Survival
timeFrame: Through study completion, from "August 28, 2017" to "January 8, 2020" (2 years and 4 months)
measure: Preliminary Tumor Activity (RR)
timeFrame: 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)
measure: Preliminary Antitumor Activity (DCR)
timeFrame: 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)
measure: Preliminary Antitumor Activity (DOR)
timeFrame: 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)
measure: MEN1309 PK Parameter Cmax
timeFrame: Cycle 1
measure: MEN1309 PK Parameter Ctrough
timeFrame: Pre-infusion Cycle 2
measure: MEN1309 Pharmacokinetic (PK) Parameter t1/2
timeFrame: Cycle 1
measure: MEN1309 Pharmacokinetic (PK) Parameter AUC
timeFrame: Cycle 1
measure: MEN1309 (PK) Parameter CL
timeFrame: Cycle 1
measure: MEN1309 Pharmacokinetic (PK) Parameter Vd
timeFrame: Cycle 1
Other outcomes:
measure: Correlation of CD205 Expression in Tumors With Clinical Activity of MEN1309 Assessed According to RECIST 1.1 or Cheson Criteria (2014)
timeFrame: Through study completion, from "August 28, 2017" to "January 8, 2020" (2 years and 4 months)
measure: Incidence of Anti-MEN1309 Antibodies
timeFrame: Day 1 of each Cycle (each cycle is 21 days)
Locations:
city: Liège
country: Belgium
facility: CHU Sart Tilman
city: Aviano
country: Italy
facility: Centro Riferimento Oncologico
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele
city: Barcelona
country: Spain
facility: Vall d'Hebron Barcelona Hospital
city: Madrid
country: Spain
facility: START Madrid. Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Centro Integral Oncologico Clara Campal
city: Newcastle upon Tyne
country: United Kingdom
facility: NCCC Clinical Trials Pharmacy, Northern Centre for Cancer Care
Study officials:
affiliation: Vall d' Hebron Institute of Oncology (VHIO) P. Vall d'Hebron 119-129 08035 Barcelona, Spain
name: Josep Tabernero Head, Medical Oncology Department, MD PhD
role: STUDY_CHAIR
References: