Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

MEN1309 I.v. Infusion in Pts With CD205-positive Metastatic Solid Tumors and Relapsed or Refractory NHL Ph I Study (CD205SHUTTLE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03403725
Recruitment Status : Terminated (Terminated after achievement of MTD, without progressing to cohort expansion for Company decision.)
First Posted : January 19, 2018
Results First Posted : September 28, 2021
Last Update Posted : September 28, 2021
Sponsor:
Information provided by (Responsible Party):
Menarini Group

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

Condition or disease Intervention/treatment Phase
Metastatic Solid Tumors Relapsed/Refractory Non-Hodgkin Lymphoma Drug: MEN1309 Phase 1

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).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Allocation: N/A
Intervention Model: Sequential Assignment
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
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 28, 2017
Actual Primary Completion Date : October 22, 2019
Actual Study Completion Date : January 8, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: MEN1309 (Step 1-Solid Tumors)/(Step 2-NHL)

Step1: Accelerated Titration Design with 1 single pt per cohort and double dose level per cohort until grade ≥ 2 drug related toxicity. Then, study reverts to 3+3 design. Any cohort in which 1 pt experiences a DLT (along ATD or 3+3) will be expanded up to 6 pts.

Step2: MTD defined in Step 1, 3 MEN1309 dose levels will be tested (MTD-2, MTD-1, and MTD), with 6 pts per each dose level. A further MTD-3 level will be explored if 2 DLTs occur at the MTD-2 dose level.

Drug: MEN1309
MEN1309 solution for intravenous infusion once every 3 weeks




Primary Outcome Measures :
  1. Maximum-Tolerated Dose (MTD) [ Time Frame: 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.

  2. Dose-Limiting Toxicity (DLT) [ Time Frame: 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 Outcome Measures :
  1. Overall Survival [ Time Frame: 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.

  2. Progression Free Survival [ Time Frame: 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.

  3. Preliminary Tumor Activity (RR) [ 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) ]
    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.

  4. Preliminary Antitumor Activity (DCR) [ 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) ]
    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.

  5. Preliminary Antitumor Activity (DOR) [ 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) ]
    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.

  6. MEN1309 PK Parameter Cmax [ Time Frame: Cycle 1 ]
    Cmax is the maximum drug concentration

  7. MEN1309 PK Parameter Ctrough [ Time Frame: Pre-infusion Cycle 2 ]
    MEN1309 PK parameter Ctrough (Predose concentration)

  8. MEN1309 Pharmacokinetic (PK) Parameter t1/2 [ Time Frame: Cycle 1 ]
    MEN1309 Pharmacokinetic (PK) parameter t1/2 (terminal serum half-life)

  9. MEN1309 Pharmacokinetic (PK) Parameter AUC [ Time Frame: Cycle 1 ]
    MEN1309 Pharmacokinetic (PK) parameter AUC (area under curve)

  10. MEN1309 (PK) Parameter CL [ Time Frame: Cycle 1 ]
    Systemic clearance of MEN1309 Pharmacokinetic

  11. MEN1309 Pharmacokinetic (PK) Parameter Vd [ Time Frame: Cycle 1 ]
    volume of distribution based on the terminal phase


Other Outcome Measures:
  1. Correlation of CD205 Expression in Tumors With Clinical Activity of MEN1309 Assessed According to RECIST 1.1 or Cheson Criteria (2014) [ Time Frame: 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.


  2. Incidence of Anti-MEN1309 Antibodies [ Time Frame: Day 1 of each Cycle (each cycle is 21 days) ]
    Exploratory Endpoint: Immunogenicity analysis regarding the Incidence of anti-MEN1309 antibodies.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03403725


Locations
Layout table for location information
Belgium
CHU Sart Tilman
Liège, Belgium, 4000
Italy
Centro Riferimento Oncologico
Aviano, Italy, 33081
IRCCS Ospedale San Raffaele
Milano, Italy, 20132
Spain
Vall d'Hebron Barcelona Hospital
Barcelona, Spain
START Madrid. Fundacion Jimenez Diaz
Madrid, Spain, 28040
Centro Integral Oncologico Clara Campal
Madrid, Spain, 28050
United Kingdom
NCCC Clinical Trials Pharmacy, Northern Centre for Cancer Care
Newcastle upon Tyne, United Kingdom, NE7 7DN
Sponsors and Collaborators
Menarini Group
Investigators
Layout table for investigator information
Study Chair: Josep Tabernero Head, Medical Oncology Department, MD PhD Vall d' Hebron Institute of Oncology (VHIO) P. Vall d'Hebron 119-129 08035 Barcelona, Spain
  Study Documents (Full-Text)

Documents provided by Menarini Group:
Study Protocol  [PDF] August 31, 2018
Statistical Analysis Plan  [PDF] January 7, 2020

Layout table for additonal information
Responsible Party: Menarini Group
ClinicalTrials.gov Identifier: NCT03403725    
Other Study ID Numbers: MEN1309-01
First Posted: January 19, 2018    Key Record Dates
Results First Posted: September 28, 2021
Last Update Posted: September 28, 2021
Last Verified: February 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Menarini Group:
Solid Tumors
Non-Hodgkin Lymphoma
NHL
MEN1309
CD205
Relapsed
Refractory
R-R NHL
ADC
Antibody-Drug Coniugate
Metastatic Tumors
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases