Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

All Drugs and Chemicals

Immunomodulating Agents

patients treated by Belantamab Mafodotin with a refractory multiple myeloma and an ophthalmologic follow-up between January 2020 and February 2022 will be included.

Data will be collected for patients coming from multiple French centers which followed patients treated by Belantamab Mafodotin between January 2020 and February 2022. They will be obtained by contacting centers through an email sent with a secure mail address.

The collected data are : sex, age, date of first immunotherapy cycle, dose, date of first consultation, objective refraction in spheric equivalent, keratometry, visual acuity, microcyst-like epithelial changes (MECs), location and density, corneal toxicity grade and complementary exams (topography, in vivo confocal microscopy).

Collection of datas

Marie Caroline TRONE, MD

Belantamab Mafodotin is the first antibody conjugate targeting B-cell maturation antigen (BCMA) in relapsed or refractory multiple myeloma (RRMM). It is used in multiple myeloma refractory to an immunomodulatory drug or proteasome inhibitor and refractory and/or intolerant to an anti-CD38 monoclonal antibody.

It has been found that the immunotherapy causes corneal side effects, Microcyst-like Epithelial Changes (MECs). They are round-shaped corneal inclusions that migrate from the peripheral cornea to the center, causing blurry vision, dryness and refractive shifts depending on their location and density.

This study aims at analysing the refractive shifts caused by Microcyst-like Epithelial Changes (MECs) and whether it can be used to monitor patients and facilitate their follow up.

Constitution of a French multicenter cohort.

Corneal Toxicity in Patients Treated by Belantamab Mafodotin

Corneal Toxicity in Patients Treated by Belantamab Mafodotin : How to Improve and Facilitate Patients Follow-up Using Refractive Shift ?

This scale is defined by 4 values : G1, G2, G3 and G4 (the best value is G1)

The severity grade of microcyst-like epithelial changes (MECs) is rated using the Keratopathy and Visual Acuity (KVA) scale after slit lamp examination.

The aim is to show a correlation between refractive shift and severity grade of microcyst-like epithelial changes (MECs)

The refraction is measured in spheric equivalent (SEQ) with an automated refractometer

The aim is to show a correlation between refractive shift and severity grade of microcyst-like epithelial changes (MECs)

The score is from 10/10 (best visual acuity) to 1/10 (worth visual acuity) Correlation between visual acuity and severity grade of microcyst-like epithelial changes (MECs)

Keratometry is measured in diopter using an autorefractometer or a topograph. This device measures the curvature of the anterior corneal surface based on the power of a reflecting surface. It does this by measuring the size of an image reflected from 2 paracentral points and utilizes doubling prisms to stabilize the image enabling more accurate focusing.

Correlation between keratometry and severity grade of microcyst-like epithelial changes (MECs)

Epithelial pachymetry is measured in micrometer (µm) using a topograph

Correlation between epithelial pachymetry and severity grade of microcyst-like epithelial changes (MECs)

Centre Hospitalier Universitaire de Saint Etienne

Lymphoma

Leukemia

Hematologic Neoplasms

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Lymphoma, Non-Hodgkin

Lymphatic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Lymphosarcoma

Acute Non Lymphoblastic Leukemia

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Acute Graft Versus Host Disease

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Daratumumab

Immunoglobulins

Experimental: GEN3014 Participants in Dose Escalation phase with

* Relapsed or refractory myeloid myeloma (RRMM)
* R/R acute myeloid leukemia (AML)

Participants in Expansion Part A with

* RRMM (anti-CD38 mAb-naïve)
* RRMM (anti-CD38 mAb-refractory)
* R/R diffuse large B-cell lymphoma (DLBCL)
* R/R AML

Participants in Expansion Part B with

• RRMM (anti-CD38 mAb-naïve)

Participants in Expansion Part B with

- RRMM (anti-CD38 mAb-naïve)

GEN3014

Daratumumab is administered by SC injections.

Genmab Trial Information

Study Official

The drug that will be investigated in the study is an antibody, GEN3014. Since this is the first study of GEN3014 in humans, the main purpose is to evaluate safety. Besides safety, the study will determine the recommended GEN3014 dose to be tested in a larger group of participants and assess preliminary clinical activity of GEN3014. GEN3014 will be studied in relapsed or refractory multiple myeloma (also known as RRMM) and other blood cancers. The study consists of 3 parts:

1. The Dose Escalation will test increasing doses of GEN3014 to find a safe dose level to be tested in the other two parts.
2. Expansion Part A will further test the GEN3014 dose determined from the Dose Escalation Part.
3. Expansion Part B will compare intravenous (IV) GEN3014 with the subcutaneous (SC) daratumumab in ex-US countries.

Participants will receive either GEN3014 or daratumumab; none will be given placebo. The study duration will be different for the individual participants. Overall, the study may be ongoing up to 5 years after the last participant's first treatment.

This trial will be conducted in 3 parts: Dose Escalation (phase 1), Expansion Parts, A and B (phase 2).

In the dose escalation phase GEN314 will be evaluated in RRMM and relapsed and refractory acute myeloid leukemia (R/R AML). The participants will receive GEN3014 administered at various dose levels in 28 day cycles. Dose Limiting Toxicities (DLTs) will be assessed during the first treatment cycle and the Maximum Tolerated Dose (MTD) and/or Recommended phase 2 dose (RP2D) will be determined.

In Expansion Part A, GEN3014 will be further evaluated in 4 cohorts: anti-CD38 monoclonal antibody (mAb)-naive RRMM, anti-CD38 mAb-refractory RRMM, relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL), and R/R AML at the RP2D identified from the Dose Escalation per protocol. In Expansion Part B, GEN3014 IV will be compared to daratumumab SC, head-to-head (H2H) to evaluate whether GEN3014 may be more potent in anti-CD38 mAb-naïve RRMM participants.

Dose escalation part is sequential while the expansion Part A cohorts are parallel. Expansion Part B is sequential to Expansion Part A RRMM cohort. In Expansion Part B, participants with RRMM are randomized (1:1) to treatment.

GEN3014 Safety Trial in Relapsed or Refractory Hematologic Malignancies

An Open-Label, Multicenter, Phase 1/2 Trial of GEN3014 (HexaBody®-CD38) in Relapsed or Refractory Multiple Myeloma and Other Hematologic Malignancies

To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) to be studied in the Expansion part. DLT will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.

ORR is defined as the percentage of participants with a partial response (PR), or better based on International Myeloma Working Group (IMWG) criteria for MM participants, based on Lugano criteria for DLBCL participants, and based on International Working Group (IWG) response criteria for AML participants.

ORR is defined as the percentage of participants with a PR, or better based on IMWG criteria.

ORR is defined as the percentage of participants with a PR or better based on IMWG criteria for MM participants, and based on IWG response criteria for AML participants.

CBR was determined by the investigator according to the IMWG response criteria for MM participants.

DOR is defined as time from first response (PR or better) to time of disease progression or death (due to any cause), whichever comes first based on IMWG criteria for MM participants and based on IWG response criteria for AML participants.

TTR is defined as the time from date of first dose to time of response (PR or better) based on IMWG criteria for MM participants and based on IWG response criteria for AML participants.

PFS is defined as the time from the date of the first dose to the date of progression or death (due to any cause), whichever comes first based on IMWG criteria for MM participants and based on IWG response criteria for AML participants.

OS is defined as the time from the date of first dose to the date of death due to any cause.

DOR is defined as time from first response (PR or better) to time of disease progression or death (due to any cause), whichever comes first based on IMWG criteria for MM participants, based on Lugano criteria for DLBCL participants, and based on IWG response criteria for AML participants.

TTR is defined as the time from date of first dose to time of response (PR or better) for MM participants, based on Lugano criteria for DLBCL participants, and based on IWG response criteria for AML participants.

PFS is defined as the time from the date of the first dose to the date of progression or death (due to any cause), whichever comes first based on IMWG criteria for MM participants, based on Lugano criteria for DLBCL participants, and based on IWG response criteria for AML participants.

DOR is defined as time from first response (PR or better) to time of disease progression or death (due to any cause), whichever comes first based on IMWG criteria for MM participants.

TTR is defined as the time from date of randomization, to time of response (PR or better) based on IMWG criteria for MM participants.

PFS is defined as the time from date of randomization to the date of progression or death (due to any cause), whichever comes first based on IMWG criteria for MM participants.

OS is defined as the time from date of randomization to the date of death due to any cause.

Time to next therapy (TTNT) for participants in the Expansion Part B is defined as the time from date of randomization to the start of subsequent anti-cancer therapy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Corneal Toxicity in Patients Treated by Belantamab Mafodotin	NCT05887206	Myeloma Multipl...	Collection of d...	18 Years -	Centre Hospitalier Universitaire de Saint Etienne
GEN3014 Safety Trial in Relapsed or Refractory Hematologic Malignancies	NCT04824794	Relapsed or Ref... Diffuse Large B... Acute Myeloid L...	GEN3014 Daratumumab	18 Years -	Genmab
Corneal Toxicity in Patients Treated by Belantamab Mafodotin	NCT05887206	Myeloma Multipl...	Collection of d...	18 Years -	Centre Hospitalier Universitaire de Saint Etienne

Spots Global Cancer Trial Database for relapsed or refractory multiple myeloma (rrmm)