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

NCT03403725 | Terminated Phase 1 Results

• 1 other identifier: MEN1309-01
• Study Type: interventional
• Target: 28
• Locations: 4 countries
• Sites: 7

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

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (11)

• Overall Survival

  Through study completion, from "August 28, 2017" to "January 8, 2020" (2 years and 4 months)

• Progression Free Survival

  Through study completion, from "August 28, 2017" to "January 8, 2020" (2 years and 4 months)

• 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 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 (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)

Other Outcomes (2)

• 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)

• Incidence of Anti-MEN1309 Antibodies

  Day 1 of each Cycle (each cycle is 21 days)

Study Arms (1)

MEN1309 (Step 1-Solid Tumors)/(Step 2-NHL)

EXPERIMENTAL

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

Interventions

MEN1309 DRUG

MEN1309 solution for intravenous infusion once every 3 weeks

MEN1309 (Step 1-Solid Tumors)/(Step 2-NHL)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged ≥ 18 years.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2.
• Neutrophil count ≥ 1,500/µL; platelets ≥ 100,000/µL; haemoglobin ≥ 9 g/dL.
• Adequate renal and hepatic laboratory assessments.
• Life expectancy of at least 2 months.
• Woman of childbearing potential (WOCBP) who agrees to use highly effective contraception (see Appendix I).

You may not qualify if:

• Central nervous system involvement (excluding treated stable cerebral metastasis, not requiring therapy to control symptoms in the last 60 days).
• Pregnant or breastfeeding women.
• 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.
• 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.
• Have significant, uncontrolled, or active cardiovascular disease.

Sponsors & Collaborators

• Menarini Group: lead

Study Sites (7)

CHU Sart Tilman

Liège, 4000, Belgium

Location

Centro Riferimento Oncologico

Aviano, 33081, Italy

Location

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

Location

Vall d'Hebron Barcelona Hospital

Barcelona, Spain

Location

START Madrid. Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Centro Integral Oncologico Clara Campal

Madrid, 28050, Spain

Location

NCCC Clinical Trials Pharmacy, Northern Centre for Cancer Care

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Recurrence; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes

Results Point of Contact

• Title: Corporate Director of Clinical Sciences
• Organization: Menarini Ricerche SPA

acapriati@menarini-ricerche.it

+39 055 56809933

Study Officials

• 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 CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: January 4, 2018
• First Posted: January 19, 2018
• Study Start: August 28, 2017
• Primary Completion: October 22, 2019
• Study Completion: January 8, 2020
• Last Updated: September 28, 2021
• Results First Posted: September 28, 2021

Record last verified: 2021-02

Locations

ES (3); BE (1); GB (1); IT (2)