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

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

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

Study Overview

• Status: Terminated
• Conditions: Metastatic Solid Tumors; Relapsed/Refractory Non-Hodgkin Lymphoma
• Intervention / Treatment: Drug: MEN1309

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).

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Liège, Belgium, 4000
    • CHU Sart Tilman
• Italy
  • Aviano, Italy, 33081
    • Centro Riferimento Oncologico
  • Milano, Italy, 20132
    • IRCCS Ospedale San Raffaele
• Spain
  • Barcelona, Spain
    • Vall d'Hebron Barcelona Hospital
  • Madrid, Spain, 28050
    • Centro Integral Oncológico Clara Campal
  • Madrid, Spain, 28040
    • START Madrid. Fundacion Jimenez Diaz
• United Kingdom
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • NCCC Clinical Trials Pharmacy, Northern Centre for Cancer Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	21-day period after the first dose
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).	21-day period after the first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Timeframe between the first study drug administration and death from any cause.	Through study completion, from "August 28, 2017" to "January 8, 2020" (2 years and 4 months)
Progression Free Survival	The Number of days between the first study administration to the date of first documented disease progression.	Through study completion, from "August 28, 2017" to "January 8, 2020" (2 years and 4 months)
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.	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)	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.	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 (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.	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)
MEN1309 PK Parameter Cmax	Cmax is the maximum drug concentration	Cycle 1
MEN1309 PK Parameter Ctrough	MEN1309 PK parameter Ctrough (Predose concentration)	Pre-infusion Cycle 2
MEN1309 Pharmacokinetic (PK) Parameter t1/2	MEN1309 Pharmacokinetic (PK) parameter t1/2 (terminal serum half-life)	Cycle 1
MEN1309 Pharmacokinetic (PK) Parameter AUC	MEN1309 Pharmacokinetic (PK) parameter AUC (area under curve)	Cycle 1
MEN1309 (PK) Parameter CL	Systemic clearance of MEN1309 Pharmacokinetic	Cycle 1
MEN1309 Pharmacokinetic (PK) Parameter Vd	volume of distribution based on the terminal phase	Cycle 1

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Through study completion, from "August 28, 2017" to "January 8, 2020" (2 years and 4 months)
Incidence of Anti-MEN1309 Antibodies	Exploratory Endpoint: Immunogenicity analysis regarding the Incidence of anti-MEN1309 antibodies.	Day 1 of each Cycle (each cycle is 21 days)

Collaborators and Investigators

• Sponsor: Menarini Group
• Investigators: 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 record dates

Study Major Dates

• Study Start (ACTUAL): August 28, 2017
• Primary Completion (ACTUAL): October 22, 2019
• Study Completion (ACTUAL): January 8, 2020

Study Registration Dates

• First Submitted: January 4, 2018
• First Submitted That Met QC Criteria: January 10, 2018
• First Posted (ACTUAL): January 19, 2018

Study Record Updates

• Last Update Posted (ACTUAL): September 28, 2021
• Last Update Submitted That Met QC Criteria: August 31, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Relapsed; Refractory; NHL; Solid Tumors; Non-Hodgkin Lymphoma; ADC; Metastatic Tumors; MEN1309; CD205; R-R NHL; Antibody-Drug Coniugate
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: MEN1309-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No