Study to Separately Evaluate the Activity of Talacotuzumab (JNJ-56022473) or Daratumumab in Transfusion-Dependent Participants With Low or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) Who Are Relapsed or Refractory to Erythropoiesis-Stimulating Agent (ESA) Treatment

A Phase 2 Proof-of-Concept Study to Separately Evaluate the Activity of Talacotuzumab (JNJ-56022473) or Daratumumab in Transfusion-Dependent Subjects With Low or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) Who Are Relapsed or Refractory to Erythropoiesis-Stimulating Agent (ESA) Treatment

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03011034

Enrollment

Registered

2017-01-05

Start date

2017-02-14

Completion date

2021-10-05

Last updated

2025-03-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Myelodysplastic Syndromes

Brief summary

The main purpose of the study is to evaluate the efficacy (transfusion independence \[TI\]) of talacotuzumab (JNJ-56022473) or daratumumab in transfusion-dependent participants with low or intermediate-1 risk Myelodysplastic Syndrome (MDS) whose disease has relapsed during treatment with or is refractory to Erythropoiesis-Stimulating Agent (ESAs).

Detailed description

This is a multicenter, randomized (study drug assigned by chance), open-label (participants and researchers are aware of the treatment participants are receiving) study to evaluate the safety and efficacy of talacotuzumab or daratumumab. Approximately 60 participants (30 to receive talacotuzumab and 30 to receive daratumumab) will be enrolled and then assigned randomly on a 1:1 basis to receive either talacotuzumab or daratumumab. The study consists of: a Screening Phase of up to 28 days during which participant eligibility will be reviewed and approved by the sponsor prior to randomization, a Treatment Phase that will extend from the first dose on Cycle 1 Day 1 until study drug discontinuation, and a Post-treatment Follow up Phase beginning once the participant discontinues talacotuzumab or daratumumab. Study drugs will continue to be administered until disease progression, lack of response, unacceptable toxicity, withdrawal of consent, or study end. Safety will be monitored throughout the study. The talacotuzumab arm of the study is closed for enrollment.

Interventions

DRUGTalacotuzumab

Talacotuzumab 9 mg/kg will be administered as an IV infusion.

DRUGDaratumumab

Daratumumab 16 mg/kg will be administered as an IV infusion.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Myelodysplastic Syndrome (MDS) according to World Health Organization (WHO) criteria confirmed by bone marrow aspirate and biopsy within 12 weeks prior to first dose. A local laboratory report from this diagnostic bone marrow aspirate and biopsy must be approved by the sponsor * International Prognostic Scoring System (IPSS) low risk or intermediate-1 risk MDS * Red blood cell (RBC) transfusion dependent, 1) Received at least 4 units of RBCs over any 8 consecutive weeks during the 16 weeks prior to randomization, 2) Pretransfusion Hb must have been less than or equal to (\<=)9.0 gram per deciliter (g/dL) * Adequate iron stores, defined as transferrin saturation greater than 20 percent (%) and serum ferritin greater than 400 nanogram per Milliliter (ng/mL), measured within the screening period, or adequate iron stores as demonstrated by recent (within 12 weeks prior to first dose) bone marrow examination with iron stain * Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2

Exclusion criteria

* Known allergies, hypersensitivity, or intolerance to talacotuzumab and daratumumab or their excipients * Received any chemotherapy, immunomodulatory or immunosuppressive therapy, corticosteroids (greater than \[\>\]30 milligram per day \[mg/day\] prednisone or equivalent) within 28 days prior to randomization * Received other treatments for MDS within 28 days prior to first dose (example \[eg\], azacitidine, decitabine, lenalidomide, Erythropoiesis-Stimulating Agent (ESA) (8 weeks for long-acting ESAs) * History of hematopoietic stem cell transplant * Del(5q) karyotype unless treatment with lenalidomide has failed. Failure is defined as either: 1) having received at least 3 months of lenalidomide treatment without RBC transfusion benefit (International Working Group \[IWG\] 2006); 2) progression or relapse after hematologic improvement with lenalidomide (IWG 2006); 3) discontinuation of lenalidomide due to toxicity; or 4) unable to receive lenalidomide due to a contraindication. Source documentation for lenalidomide treatment failure must be verified by the sponsor

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence (TI) Lasting at Least 8 Weeks	Up to 2 years	Percentage of participants who achieved RBC TI lasting at least 8 weeks were reported. RBC TI was defined as absence of RBC transfusion during any consecutive 56 days (8 weeks) post randomization.

Secondary

Measure	Time frame	Description
Time to Transfusion Independence (TI)	Up to 2 years	Time to transfusion independence (TI) was defined as time to the start of the TI interval. TI was defined as absence of RBC transfusion during any consecutive 56 days (8 weeks) post randomization.
Duration of Transfusion Independence (TI)	Up to 2 years	Duration of TI was reported. TI was defined as absence of RBC transfusion during any consecutive 56 days (8 weeks) post randomization.
Percentage of Participants Who Met IWG Criteria for Transfusion Reduction	Up to 2 years	Percentage of participants who met IWG criteria for transfusion reduction were reported. IWG criteria for transfusion reduction: at least 4 units reduction in RBC transfusions in the best 8-week interval. The best 8-week interval was a post-baseline 8-week interval where the participant had the fewest post-baseline RBC transfusion units.
Percentage of Participants With at Least One Dose of Myeloid Growth Factors Usage	Up to 2 years	Percentage of participants with Myeloid Growth Factors (MGF) usage (who had used at least 1 dose of MGF) were reported.
Percentage of Participants With Hematologic Improvement (HI) Per IWG 2006 by Investigator Assessment	Up to 2 years	Percentage of participants with HI per International Working Group (IWG) 2006 by investigator assessment were reported. Response criteria per IWG 2006 for HI: Erythroid response (pretreatment, less than \[\<\]11 gram per deciliter \[g/dL\]) - hemoglobin increase by greater than or equal to (\>=)1.5 g/dL, relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 weeks compared with the pretreatment transfusion number in the previous 8 weeks. Only RBC transfusions given for a Hb of \<=9 g/dL pretreatment counted in the RBC transfusion response evaluation; Platelet response (pretreatment, \<100\10\^9/L) - absolute increase of \>=30\10\^9/L for participants starting with \>20\10\^9/L platelets. Increase from \<20\10\^9/L to \>20\10\^9/L and by at least 100 percent (%); Neutrophil response (pretreatment, \<1\10\^9/L) - at least 100% increase and an absolute increase \>0.5\*10\^9/L.
Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence (TI) Lasting at Least 24 Weeks	Up to 2 years	Percentage of participants who achieved RBC TI lasting at least 24 weeks were reported. RBC TI was defined as absence of RBC transfusion during any consecutive 56 days (8 weeks) post randomization.
Percentage of Participants With Partial Remission (PR)	Up to 2 years	Percentage of participants with PR were reported. PR per International Working Group (IWG) 2006 Response criteria: All CR criteria if abnormal before treatment except: Bone marrow blasts decreased by \>=50% over pretreatment but still \>5%, cellularity and morphology not relevant.
Percentage of Participants With Cytogenetic Response	Up to 2 years	Percentage of participants with cytogenetic response were reported. Cytogenetic response per International Working Group (IWG) 2006 Response criteria: Complete - disappearance of the chromosomal abnormality without appearance of new ones; Partial - at least 50% reduction of the chromosomal abnormality.
Overall Survival	Up to 2 years	The overall survival was defined as the time from the date of first dose of study drug to date of death from any cause. Median overall survival was estimated by using the Kaplan-Meier method.
Time to Progression to Acute Myeloid Leukemia (AML)	Up to 2 years	Time to progression to acute myeloid leukemia was reported. Disease progression as per IWG response criteria: For participants with: \<5% blasts: \>=50% increase in blasts to \>5% blasts; 5%-10% blasts: \>=50% increase to \>10% blasts; 10%-20% blasts: \>=50% increase to \>20% blasts; 20%-30% blasts: \>=50% increase to \>30% blasts. Any of the following: \>=50% decrement from maximum remission/response in granulocytes or platelets; reduction in hemoglobin by \>=2 g/dL; transfusion dependence.
Percentage of Participants With Complete Remission (CR) and Marrow CR	Up to 2 years	Percentage of participants with CR and marrow CR were reported. CR per International Working Group (IWG) 2006 Response criteria: Bone marrow - less than or equal to (\<=)5% myeloblasts with normal maturation of all cell lines, persistent dysplasia noted; Peripheral blood - hemoglobin \>=11 g/dL; platelets \>=100\10\^9/L; neutrophils \>=1.0\10\^9/L; blasts, 0%. Marrow CR: Bone marrow - \<=5% myeloblasts and decrease by \>=50% over pretreatment; Peripheral blood - if HI responses, they were noted in addition to marrow CR.

Countries

Belgium, Italy, Netherlands, Russia, Spain, United States

Participant flow

Recruitment details

Out of 34 enrolled participants, 33 participants received daratumumab and 1 participant received talacotuzumab.

Pre-assignment details

Due to serious infusion-related reaction (IRR) event that occurred in first participant enrolled in talacotuzumab arm, no further participants were enrolled in this arm.

Participants by arm

Arm	Count
Talacotuzumab Participant received a single dose of talacotuzumab 9 milligram per kilogram (mg/kg) intravenously (IV).	1
Daratumumab Participants received daratumumab 16 mg/kg IV weekly on Weeks 1 to 8 (on Days 1, 8, 15, and 22 for Cycles 1 and 2), every 2 weeks for Weeks 9 to 24 (on Days 1 and 15 for Cycles 3 to 6), and every 4 weeks thereafter (on Day 1 for all subsequent cycles). Each treatment cycle was 28 days.	33
Total	34

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	1	0

Baseline characteristics

Characteristic	Talacotuzumab	Total	Daratumumab
Age, Continuous	67 years	71.4 years STANDARD_DEVIATION 6.8	71.5 years STANDARD_DEVIATION 6.86
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	4 Participants	4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants	28 Participants	27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	2 Participants	2 Participants
Race/Ethnicity, Customized Other	0 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized Unknown or Not Reported	0 Participants	3 Participants	3 Participants
Race/Ethnicity, Customized White	1 Participants	30 Participants	29 Participants
Region of Enrollment BELGIUM	1 Participants	7 Participants	6 Participants
Region of Enrollment ITALY	0 Participants	3 Participants	3 Participants
Region of Enrollment NETHERLANDS	0 Participants	3 Participants	3 Participants
Region of Enrollment RUSSIAN FEDERATION	0 Participants	3 Participants	3 Participants
Region of Enrollment SPAIN	0 Participants	10 Participants	10 Participants
Region of Enrollment UNITED STATES	0 Participants	8 Participants	8 Participants
Sex: Female, Male Female	0 Participants	8 Participants	8 Participants
Sex: Female, Male Male	1 Participants	26 Participants	25 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 1	6 / 33
other Total, other adverse events	1 / 1	33 / 33
serious Total, serious adverse events	1 / 1	15 / 33

Outcome results

Primary

Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence (TI) Lasting at Least 8 Weeks

Percentage of participants who achieved RBC TI lasting at least 8 weeks were reported. RBC TI was defined as absence of RBC transfusion during any consecutive 56 days (8 weeks) post randomization.

Time frame: Up to 2 years

Population: Intent-to-treat (ITT) population included all participants who received at least 1 dose of study drug.

Arm	Measure	Value (NUMBER)
Talacotuzumab	Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence (TI) Lasting at Least 8 Weeks	0 Percentage of participants
Daratumumab	Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence (TI) Lasting at Least 8 Weeks	6.1 Percentage of participants

Secondary

Duration of Transfusion Independence (TI)

Duration of TI was reported. TI was defined as absence of RBC transfusion during any consecutive 56 days (8 weeks) post randomization.

Time frame: Up to 2 years

Population: ITT population who achieved TI for at least 8 weeks. As less number of participants were evaluable for this outcome measure (OM), the results were not summarized. Hence, participant wise data is reported.

Arm	Measure	Group	Value (NUMBER)
Talacotuzumab	Duration of Transfusion Independence (TI)	Participant 3	NA Weeks
Daratumumab	Duration of Transfusion Independence (TI)	Participant 1	16 Weeks
Daratumumab	Duration of Transfusion Independence (TI)	Participant 2	65 Weeks

Secondary

Overall Survival

The overall survival was defined as the time from the date of first dose of study drug to date of death from any cause. Median overall survival was estimated by using the Kaplan-Meier method.

Time frame: Up to 2 years