HORIZON: A Study of Melphalan Flufenamide (Melflufen) Plus Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

• Sponsor: Oncopeptides AB (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02963493
• Collaborator: Precision For Medicine (Industry)
• Enrollment: 157
• Locations: 20
• Arm: 1
• Actual Duration (Months): 58.6
• Patients Per Site: 7.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study will evaluate melflufen in combination with dexamethasone in adult patients with relapsed or refractory multiple myeloma in whose disease is refractory to pomalidomide and/or an anti-CD38 monoclonal antibody. All patients in the study will be treated with melflufen on Day 1 and dexamethasone on Days 1, 8, 15 and 22 of each 28-day cycle.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Melphalan flufenamide (Melflufen); Drug: Dexamethasone	Phase 2

Detailed Description

Melphalan flufenamide (melflufen) is a peptide-drug conjugate that rapidly delivers an alkylating payload into tumor cells. Peptidases are expressed in several cancers, including solid tumors and hematologic malignancies. Melphalan flufenamide is rapidly taken up by myeloma cells due to its high lipophilicity. Once inside the myeloma cell, the activity of melphalan flufenamide is determined by its immediate cleavage by peptidases into hydrophilic alkylator payloads that are entrapped. Melphalan flufenamide is 50-fold more potent than melphalan in myeloma cells in vitro due to increased intracellular alkylator concentration. It rapidly induces irreversible DNA damage leading to apoptosis of myeloma cells. Melphalan flufenamide displays cytotoxic activity against myeloma cell lines resistant to other treatments, including alkylators, in vitro. Melphalan flufenamide also has demonstrated inhibition of angiogenesis and DNA damage with a lack of functional DNA repair in preclinical studies.

Study Design

• Study Type: Interventional
• Actual Enrollment: 157 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Single Arm, Open-Label, Phase 2 Study of Melflufen in Combination With Dexamethasone in Patients With Relapsed Refractory Multiple Myeloma Who Are Refractory to Pomalidomide and/or an Anti-CD38 Monoclonal Antibody
• Actual Study Start Date: Dec 28, 2016
• Actual Primary Completion Date: Oct 22, 2020
• Actual Study Completion Date: Nov 16, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: melphalan flufenamide (melflufen) + dexamethasone Melphalan flufenamide (melflufen) 40 mg Day 1 and dexamethasone 40 mg (20 mg for patients 75 years or older) on Days 1, 8, 15 and 22 of each 28-day cycle.	Drug: Melphalan flufenamide (Melflufen); Other Names: Pepaxto ; Drug: Dexamethasone; IV dexamethasone may be substituted for oral dexamethasone in the US. Oral only in Europe.

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (ORR) [Patients were followed until documented progression, unacceptable toxicity, patient/physician decision to withdraw or date of death, whichever came first. Longest time to response in study recorded as 7.4 months. Longest time on study 17 months.]

   The overall response rate (ORR) will be estimated as the percentage of patients who achieve sCR, CR, VGPR, or PR as their best response as assessed by the investigator. Response assessed by IMWG (International myeloma working group) criteria sCR-stringent complete response: CR plus Normal FLC (free light chain) ratio and absence of clonal cells in BM CR-complete response: Negative immunofixation in serum/urine; Disappearance of soft tissue plasmacytomas; <5% plasma cells in BM; If only FLC disease, normal FLC ratio (0.26-1.65) VGPR-very good partial response: Serum/urine M-protein detectable by immunofixation but not electrophoresis or ≥90% reduction in serum M-protein and urine M-protein <100 mg/24 h; If only FLC disease, >90% decrease in the difference between involved and uninvolved FLC levels PR-partial response: 50% reduction of serum M-protein and soft tissue plasmacytomas, ≥90% reduction in urinary M-protein or to <200 mg/24 h; other special cases if M-protein unmeasurable

Secondary Outcome Measures

1. Progression Free Survival (PFS) [Patients were followed until documented progression, unacceptable toxicity, patient/physician decision to withdraw or date of death, whichever came first. Longest time on study 17 months at data cutoff, 26 patients were still on study]

   Time from start of treatment to either progression or death, whichever comes first as assessed by the investigator using IMWG criteria. Progression of disease is defined by an increase of 25% from the lowest response for either of Serum M-component (absolute increase of ≥ 0.5 g/dL) or Urine M-component (absolute increase of ≥200 mg/ 24h); In patients without measurable M-protein a 25% increase in the difference between involved and uninvolved FLC (free light chain) levels (absolute increase must be >10 mg/dL); If unmeasurable FLC levels, a 25% increase in bone marrow plasma cell percentage (absolute percentage must be >10%); New bone or soft tissue plasmacytomas or definite increase in existing ones; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to the plasma cell proliferative disorder

2. Duration of Response [From date of response until the date of first documented progression or date of death from any cause, whichever came first. Longest time on study 17 months at data cutoff. 26 patients were still on study.]

   Time from first response to progression based on investigator assessment. See definitions of response and progression in ORR and PFS outcomes.

3. Overall Survival [From date of first dose of study medication until the date of death from any cause, assessed up to 24 months after study drug discontinuation]

   Time from start of treatment to death

4. Functional Status and Well-being: EORTC QLQ-C30 [To be assessed prior to dosing at Cycle 1, 2, 4, 6, 8, and End of Treatment. 23 patients were ongoing for QoL assessments at data cutoff. QoL was added in Protocol Amendment 4 beginning in Oct. 2018.]

   Change from baseline in Patient Reported Outcome questionnaire EORTC QLQ-C30. The EORTC QLQ-C30 includes 30 items resulting in 5 functional scales, 1 Global Health Status scale, 3 symptom scales, and 6 single items. The recall period is 1 week (the past week). The scales are transformed to a 0 (worst) to 100 (best) scale. The QLQ-C30 summary score is calculated as the mean of the combined 13 QLQ-C30 scale and item scores (excluding global QoL and financial impact), with a higher score indicating a better HRQoL. If at least 50% of the items from the scale had been answered, the missing items were assumed to have values equal to the average of those items which were present for that respondent.

5. Functional Status and Well-being: EQ-5D-3L [To be assessed prior to dosing at Cycle 1, 2, 4, 6, 8, and End of Treatment. 23 patients were ongoing for QoL assessments at data cutoff. QoL was added in Protocol Amendment 4 beginning in Oct. 2018.]

   Change from baseline in Patient Reported Outcome questionnaire EQ-5D-3L. The EQ-5D-3L questionnaire converts 5 dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression of patient-reported, current-day health status into a "health utility" score. For the EQ-5D-3L questionnaire, each dimension is scored on an ordinal scale with 3 available levels of response and scores ranging from 1 to 3, "no problems," "some problems," and "extreme problems," respectively. The EQ VAS scores rates "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). No imputation of missing items or composite scores were done. The scores for the 5 dimensions are used to compute a single utility score ranging from zero (0.0) to 1 (1.0) representing the general health status of the individual.

6. Clinical Benefit Rate [Patients were followed until documented progression, unacceptable toxicity, patient/physician decision to withdraw or date of death, whichever came first. Longest time on study 17 months at data cutoff, 26 patients were still on study]

   The clinical benefit rate (CBR) will be estimated as the percentage of patients who achieve sCR, CR, VGPR, PR, or MR as their best response as assessed by the investigator. See Primary Outcome (ORR) for definitions of response categories.

7. Time to Response [From start of treatment to first confirmed response. Longest time to response in study recorded as 7.4 months.]

   Duration from start of treatment to the first occurrence of a confirmed response of PR or better as assessed by the investigator. See definitions of response in Primary Outcome (ORR).

8. Time to Progression [From start of treatment to first evidence of disease progression or date of death from any cause, whichever came first. Longest time on study 17 months at data cutoff, 26 patients were still on study.]

   Duration from start of treatment to first evidence of disease progression as assessed by the investigator. See definitions of response and progression in ORR and PFS outcomes.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female, age 18 years or older

• A prior diagnosis of multiple myeloma with documented disease progression

• Measurable disease based on either of a) serum monoclonal protein by protein electrophoresis (SPEP), b) monoclonal protein in the urine on 24-hour urine electrophoresis (UPEP), and/or c) serum immunoglobulin free light chain combined with abnormal serum immunoglobulin kappa to lambda free light chain ratio

• A minimum of 2 prior lines of therapy including an IMiD and a PI and is refractory to pomalidomide and/or daratumumab

• Life expectancy of ≥ 6 months

• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

• Female of child bearing potential (FCBP) and non-vasectomized male agree to practice appropriate methods of birth control

• Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information

• 12-lead ECG with QTc interval within defined limit

• Acceptable laboratory results during screening and prior to first study drug administration of the following parameters: absolute neutrophil count (ANC), platelet count, hemoglobin, total bilirubin, aspartate transaminase (AST/SGOT) and alanine transaminase (ALT/SGPT), renal function based on estimated creatinine clearance

• Must have, or accept to have, an acceptable central catheter for infusion of melflufen

Exclusion Criteria:

• Evidence of mucosal or internal bleeding and/or is platelet transfusion refractory

• Any medical conditions that, in the Investigator's opinion, would impose excessive risk to the patient or would adversely affect his/her participating in this study

• Known active infection requiring parenteral or oral anti-infective treatment within defined period

• Primary refractory disease

• Other malignancy diagnosed or requiring treatment within the defined period with specific exceptions

• Pregnant or breast-feeding females

• Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse compliance or follow-up evaluation

• Known HIV or active hepatitis B or C viral infection

• Concurrent symptomatic amyloidosis or plasma cell leukemia

• POEMS syndrome [plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes]

• Previous cytotoxic therapies, including cytotoxic investigational agents, for multiple myeloma within defined values prior to start of study treatment

• Residual side effects to previous therapy over specific grade prior to initiation of therapy

• Prior autologous or allogeneic stem cell transplant within defined period of initiation of therapy

• Prior allogeneic stem cell transplant with active graft-versus-host- disease (GVHD).

• Prior major surgical procedure or radiation therapy within specified period of the first dose of study treatment (with defined exception).

• Known intolerance to steroid therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Innovative Clinical Research Institute (ICRI)	Whittier	California	United States	90603
2	University of Florida	Gainesville	Florida	United States	32610
3	RUSH	Chicago	Illinois	United States	60612
4	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
5	Karmanos Cancer Center	Detroit	Michigan	United States	48201
6	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
7	Hudson Valley Hematology Oncology	Poughkeepsie	New York	United States	10532
8	UPMC Hillman Cancer Insitute	Pittsburgh	Pennsylvania	United States	15232
9	Baylor	Dallas	Texas	United States	75246
10	CHU de Nantes	Nantes		France	44000
11	CHU de Poitiers	Poitiers		France	86021
12	Universita di Bolognia	Bologna		Italy	40126
13	Turin Hospital Myeloma Unit	Turin		Italy	10126
14	Hospital Clinic i Provincial de Barcelona	Barcelona		Spain	08036
15	Institut Català d'Oncología (ICO) Badalona	Barcelona		Spain	08916
16	Hospital Universitario de La Princesa	Madrid		Spain	28006
17	Hospital Universitario Fundación Jiménez Díaz	Madrid		Spain	28040
18	Clínica Universidad de Navarra	Pamplona		Spain	31008
19	Complejo Hospitalario de Salamanca	Salamanca		Spain	37007
20	Hospital Universitario Doctor Peset	Valencia		Spain	46017

Sponsors and Collaborators

• Oncopeptides AB
• Precision For Medicine

Investigators

• Study Chair: Johan Harmenberg, MD, PhD, Oncopeptides AB

Study Documents (Full-Text)

• Study Protocol - Mar 20, 2020
• Statistical Analysis Plan - Feb 26, 2020

More Information

Publications

None provided.

• Responsible Party: Oncopeptides AB
• ClinicalTrials.gov Identifier: NCT02963493
• Other Study ID Numbers: OP-106
• First Posted: Nov 15, 2016
• Last Update Posted: Feb 9, 2022
• Last Verified: Feb 1, 2022

• Keywords provided by Oncopeptides AB: relapsed refractory multiple myeloma
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Dexamethasone; Melphalan

Study Results

Participant Flow

Pre-assignment Detail	157 Patients were enrolled and treated on study

Arm/Group Title	Melphalan Flufenamide (Melflufen) + Dexamethasone: Full Analysis Set
Arm/Group Description	Melphalan flufenamide (melflufen) 40 mg Day 1 and dexamethasone 40 mg (reduced dose for patients 75 years or older) on Days 1, 8, 15 and 22 of each 28-day cycle. Melphalan flufenamide (Melflufen) Dexamethasone
Period Title: Overall Study
STARTED	157
COMPLETED	157
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Melphalan Flufenamide (Melflufen) + Dexamethasone
Arm/Group Description	Melphalan flufenamide (melflufen) 40 mg Day 1 and dexamethasone 40 mg (reduced dose for patients 75 years or older) on Days 1, 8, 15 and 22 of each 28-day cycle. Melphalan flufenamide (Melflufen) Dexamethasone
Overall Participants	157
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	78 49.7%
>=65 years	79 50.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.7 (9.63)
Sex: Female, Male (Count of Participants)
Female	89 56.7%
Male	68 43.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 3.2%
Not Hispanic or Latino	139 88.5%
Unknown or Not Reported	13 8.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 0.6%
Native Hawaiian or Other Pacific Islander	1 0.6%
Black or African American	11 7%
White	135 86%
More than one race	0 0%
Unknown or Not Reported	9 5.7%
Region of Enrollment (participants) [Number]
United States	69 43.9%
Italy	23 14.6%
France	13 8.3%
Spain	52 33.1%
ECOG Performance Status (Count of Participants)
Performance Status 0	39 24.8%
Performance Status 1	93 59.2%
Performance Status 2	25 15.9%
Weight (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	74.3 (17.41)
International Staging System (ISS) (Count of Participants)
International Staging System (ISS) Stage I	63 40.1%
International Staging System (ISS) Stage II	49 31.2%
International Staging System (ISS) Stage III	39 24.8%
Unknown	4 2.5%
Missing	2 1.3%
Time since initial diagnosis (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	7.0 (3.46)
Extramedullary disease at study entry (Count of Participants)
Count of Participants [Participants]	55 35%
Type of measurable disease at baseline (Count of Participants)
SPEP and UPEP	33 21%
SPEP only	62 39.5%
UPEP only	37 23.6%
sFLC only	20 12.7%
Unable to determine	5 3.2%
Cytogenetic risk group based on FISH at study entry (Count of Participants)
High	59 37.6%
Standard	67 42.7%
Unknown	31 19.7%
Heavy-light chain combination at study entry (Count of Participants)
IgA-Kappa	18 11.5%
IgA-Lambda	12 7.6%
IgD-Kappa	1 0.6%
IgD-Lambda	1 0.6%
IgG-Kappa	57 36.3%
IgG-Lambda	31 19.7%
IgM-Kappa	2 1.3%
Multiple-Kappa	2 1.3%
None-Kappa	19 12.1%
None-Lambda	13 8.3%
Unknown-Kappa	1 0.6%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (ORR)
Description	The overall response rate (ORR) will be estimated as the percentage of patients who achieve sCR, CR, VGPR, or PR as their best response as assessed by the investigator. Response assessed by IMWG (International myeloma working group) criteria sCR-stringent complete response: CR plus Normal FLC (free light chain) ratio and absence of clonal cells in BM CR-complete response: Negative immunofixation in serum/urine; Disappearance of soft tissue plasmacytomas; <5% plasma cells in BM; If only FLC disease, normal FLC ratio (0.26-1.65) VGPR-very good partial response: Serum/urine M-protein detectable by immunofixation but not electrophoresis or ≥90% reduction in serum M-protein and urine M-protein <100 mg/24 h; If only FLC disease, >90% decrease in the difference between involved and uninvolved FLC levels PR-partial response: 50% reduction of serum M-protein and soft tissue plasmacytomas, ≥90% reduction in urinary M-protein or to <200 mg/24 h; other special cases if M-protein unmeasurable
Time Frame	Patients were followed until documented progression, unacceptable toxicity, patient/physician decision to withdraw or date of death, whichever came first. Longest time to response in study recorded as 7.4 months. Longest time on study 17 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Melphalan Flufenamide (Melflufen) + Dexamethasone: Full Analysis Set	Melphalan Flufenamide (Melflufen) + Dexamethasone: Patients With Extramedullary Disease	Melphalan Flufenamide (Melflufen) + Dexamethasone: Patients With Triple Class Refractory Disease
Arm/Group Description	Full analysis set Melphalan flufenamide (melflufen) 40 mg Day 1 and dexamethasone 40 mg (reduced dose for patients 75 years or older) on Days 1, 8, 15 and 22 of each 28-day cycle. Melphalan flufenamide (Melflufen) Dexamethasone: IV dexamethasone may be substituted for oral dexamethasone in the US. Oral only in Europe.	Patients with extramedullary disease at baseline defined as myeloma disease either originating in, but extending beyond, the cortical bone or as a separate soft tissue mass	Triple class refractory population defined as refractory to or intolerant of at least one immunomodulatory drug, at least one proteasome inhibitor, and at least one anti-CD38 monoclonal antibody
Measure Participants	157	55	119
Count of Participants [Participants]	46 29.3%	13 NaN	31 NaN

2. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	Time from start of treatment to either progression or death, whichever comes first as assessed by the investigator using IMWG criteria. Progression of disease is defined by an increase of 25% from the lowest response for either of Serum M-component (absolute increase of ≥ 0.5 g/dL) or Urine M-component (absolute increase of ≥200 mg/ 24h); In patients without measurable M-protein a 25% increase in the difference between involved and uninvolved FLC (free light chain) levels (absolute increase must be >10 mg/dL); If unmeasurable FLC levels, a 25% increase in bone marrow plasma cell percentage (absolute percentage must be >10%); New bone or soft tissue plasmacytomas or definite increase in existing ones; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to the plasma cell proliferative disorder
Time Frame	Patients were followed until documented progression, unacceptable toxicity, patient/physician decision to withdraw or date of death, whichever came first. Longest time on study 17 months at data cutoff, 26 patients were still on study

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Melphalan Flufenamide (Melflufen) + Dexamethasone: Full Analysis Set	Melphalan Flufenamide (Melflufen) + Dexamethasone: Patients With Extramedullary Disease	Melphalan Flufenamide (Melflufen) + Dexamethasone: Patients With Triple Class Refractory Disease
Arm/Group Description	Melphalan flufenamide (melflufen) 40 mg Day 1 and dexamethasone 40 mg (reduced dose for patients 75 years or older) on Days 1, 8, 15 and 22 of each 28-day cycle. Melphalan flufenamide (Melflufen) Dexamethasone: IV dexamethasone may be substituted for oral dexamethasone in the US. Oral only in Europe.	Patients with extramedullary disease at baseline defined as myeloma disease either originating in, but extending beyond, the cortical bone or as a separate soft tissue mass	Triple class refractory population defined as refractory to or intolerant of at least one immunomodulatory drug, at least one proteasome inhibitor, and at least one anti-CD38 monoclonal antibody
Measure Participants	157	55	119
Median (95% Confidence Interval) [months]	4.24	2.89	3.94

3. Secondary Outcome

Title	Duration of Response
Description	Time from first response to progression based on investigator assessment. See definitions of response and progression in ORR and PFS outcomes.
Time Frame	From date of response until the date of first documented progression or date of death from any cause, whichever came first. Longest time on study 17 months at data cutoff. 26 patients were still on study.

Outcome Measure Data

Analysis Population Description

Patients with a best response of PR or better as determined by the investigator

Arm/Group Title	Melphalan Flufenamide (Melflufen) + Dexamethasone: Full Analysis Set	Melphalan Flufenamide (Melflufen) + Dexamethasone: Patients With Extramedullary Disease	Melphalan Flufenamide (Melflufen) + Dexamethasone: Patients With Triple Class Refractory Disease
Arm/Group Description	Melphalan flufenamide (melflufen) 40 mg Day 1 and dexamethasone 40 mg (reduced dose for patients 75 years or older) on Days 1, 8, 15 and 22 of each 28-day cycle. Melphalan flufenamide (Melflufen) Dexamethasone: IV dexamethasone may be substituted for oral dexamethasone in the US. Oral only in Europe.	Patients with extramedullary disease at baseline defined as myeloma disease either originating in, but extending beyond, the cortical bone or as a separate soft tissue mass	Triple class refractory population defined as refractory to or intolerant of at least one immunomodulatory drug, at least one proteasome inhibitor, and at least one anti-CD38 monoclonal antibody
Measure Participants	46	55	119
Median (95% Confidence Interval) [months]	5.49	5.49	4.40

4. Secondary Outcome

Title	Overall Survival
Description	Time from start of treatment to death
Time Frame	From date of first dose of study medication until the date of death from any cause, assessed up to 24 months after study drug discontinuation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Melphalan Flufenamide (Melflufen) + Dexamethasone: Full Analysis Set	Melphalan Flufenamide (Melflufen) + Dexamethasone: Patients With Extramedullary Disease	Melphalan Flufenamide (Melflufen) + Dexamethasone: Patients With Triple Class Refractory Disease
Arm/Group Description	Melphalan flufenamide (melflufen) 40 mg Day 1 and dexamethasone 40 mg (reduced dose for patients 75 years or older) on Days 1, 8, 15 and 22 of each 28-day cycle. Melphalan flufenamide (Melflufen) Dexamethasone: IV dexamethasone may be substituted for oral dexamethasone in the US. Oral only in Europe.	Patients with extramedullary disease at baseline defined as myeloma disease either originating in, but extending beyond, the cortical bone or as a separate soft tissue mass	Triple class refractory population defined as refractory to or intolerant of at least one immunomodulatory drug, at least one proteasome inhibitor, and at least one anti-CD38 monoclonal antibody
Measure Participants	157	55	119
Median (95% Confidence Interval) [months]	11.63	6.47	11.24

5. Secondary Outcome

Title	Functional Status and Well-being: EORTC QLQ-C30
Description	Change from baseline in Patient Reported Outcome questionnaire EORTC QLQ-C30. The EORTC QLQ-C30 includes 30 items resulting in 5 functional scales, 1 Global Health Status scale, 3 symptom scales, and 6 single items. The recall period is 1 week (the past week). The scales are transformed to a 0 (worst) to 100 (best) scale. The QLQ-C30 summary score is calculated as the mean of the combined 13 QLQ-C30 scale and item scores (excluding global QoL and financial impact), with a higher score indicating a better HRQoL. If at least 50% of the items from the scale had been answered, the missing items were assumed to have values equal to the average of those items which were present for that respondent.
Time Frame	To be assessed prior to dosing at Cycle 1, 2, 4, 6, 8, and End of Treatment. 23 patients were ongoing for QoL assessments at data cutoff. QoL was added in Protocol Amendment 4 beginning in Oct. 2018.

Outcome Measure Data

Analysis Population Description

Number of patients with available data for summary score computation. Results not reported for patients with Extramedullary Disease.

Arm/Group Title	Melphalan Flufenamide (Melflufen) + Dexamethasone: Full Analysis Set	Melphalan Flufenamide (Melflufen) + Dexamethasone: Patients With Triple Class Refractory Disease
Arm/Group Description	Melphalan flufenamide (melflufen) 40 mg Day 1 and dexamethasone 40 mg (reduced dose for patients 75 years or older) on Days 1, 8, 15 and 22 of each 28-day cycle. Melphalan flufenamide (Melflufen) Dexamethasone: IV dexamethasone may be substituted for oral dexamethasone in the US. Oral only in Europe.	Triple class refractory population defined as refractory to or intolerant of at least one immunomodulatory drug, at least one proteasome inhibitor, and at least one anti-CD38 monoclonal antibody
Measure Participants	62	48
Baseline value	75.5 (13.2)	74.9 (13.0)
Cycle 2 Day 1 Change from baseline	0.2 (11.9)	74.8 (13.7)
Cycle 4 Day 1 Change from baseline	-2.6 (12.8)	76.9 (11.9)
Cycle 6 Day 1 Change from baseline	-3.3 (11.5)	73.2 (12.6)
Cycle 8 Day 1 Change from baseline	-7.5 (10.6)	71.3 (11.3)

6. Secondary Outcome

Title	Functional Status and Well-being: EQ-5D-3L
Description	Change from baseline in Patient Reported Outcome questionnaire EQ-5D-3L. The EQ-5D-3L questionnaire converts 5 dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression of patient-reported, current-day health status into a "health utility" score. For the EQ-5D-3L questionnaire, each dimension is scored on an ordinal scale with 3 available levels of response and scores ranging from 1 to 3, "no problems," "some problems," and "extreme problems," respectively. The EQ VAS scores rates "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). No imputation of missing items or composite scores were done. The scores for the 5 dimensions are used to compute a single utility score ranging from zero (0.0) to 1 (1.0) representing the general health status of the individual.
Time Frame	To be assessed prior to dosing at Cycle 1, 2, 4, 6, 8, and End of Treatment. 23 patients were ongoing for QoL assessments at data cutoff. QoL was added in Protocol Amendment 4 beginning in Oct. 2018.

Outcome Measure Data

Analysis Population Description

The number of patients with available data on change in health utility index at each timepoint. Results not reported for patients with Extramedullary Disease.

Arm/Group Title	Melphalan Flufenamide (Melflufen) + Dexamethasone: Full Analysis Set	Melphalan Flufenamide (Melflufen) + Dexamethasone: Patients With Triple Class Refractory Disease
Arm/Group Description	Melphalan flufenamide (melflufen) 40 mg Day 1 and dexamethasone 40 mg (reduced dose for patients 75 years or older) on Days 1, 8, 15 and 22 of each 28-day cycle. Melphalan flufenamide (Melflufen) Dexamethasone: IV dexamethasone may be substituted for oral dexamethasone in the US. Oral only in Europe.	Triple class refractory population defined as refractory to or intolerant of at least one immunomodulatory drug, at least one proteasome inhibitor, and at least one anti-CD38 monoclonal antibody
Measure Participants	62	48
Baseline value	0.6748 (0.2243)	0.6803 (0.2086)
Cycle 2 Day 1 Change from baseline	-0.0228 (0.1848)	-0.0502 (0.1846)
Cycle 4 Day 1 Change from baseline	-0.0169 (0.2187)	0.0038 (0.1919)
Cycle 6 Day 1 Change from baseline	-0.0786 (0.3049)	-0.1486 (0.3309)
Cycle 8 Day 1 Change from baseline	-0.1461 (0.2320)	-0.2174 (0.2464)
End of Treatment Change from baseline	-0.0014 (0.2594)	0.0124 (0.2552)

7. Secondary Outcome

Title	Clinical Benefit Rate
Description	The clinical benefit rate (CBR) will be estimated as the percentage of patients who achieve sCR, CR, VGPR, PR, or MR as their best response as assessed by the investigator. See Primary Outcome (ORR) for definitions of response categories.
Time Frame	Patients were followed until documented progression, unacceptable toxicity, patient/physician decision to withdraw or date of death, whichever came first. Longest time on study 17 months at data cutoff, 26 patients were still on study

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Melphalan Flufenamide (Melflufen) + Dexamethasone: Full Analysis Set	Melphalan Flufenamide (Melflufen) + Dexamethasone: Patients With Extramedullary Disease	Melphalan Flufenamide (Melflufen) + Dexamethasone: Patients With Triple Class Refractory Disease
Arm/Group Description	Melphalan flufenamide (melflufen) 40 mg Day 1 and dexamethasone 40 mg (reduced dose for patients 75 years or older) on Days 1, 8, 15 and 22 of each 28-day cycle. Melphalan flufenamide (Melflufen) Dexamethasone: IV dexamethasone may be substituted for oral dexamethasone in the US. Oral only in Europe.	Patients with extramedullary disease at baseline defined as myeloma disease either originating in, but extending beyond, the cortical bone or as a separate soft tissue mass	Triple class refractory population defined as refractory to or intolerant of at least one immunomodulatory drug, at least one proteasome inhibitor, and at least one anti-CD38 monoclonal antibody
Measure Participants	157	55	119
Count of Participants [Participants]	71 45.2%	17 NaN	47 NaN

8. Secondary Outcome

Title	Time to Response
Description	Duration from start of treatment to the first occurrence of a confirmed response of PR or better as assessed by the investigator. See definitions of response in Primary Outcome (ORR).
Time Frame	From start of treatment to first confirmed response. Longest time to response in study recorded as 7.4 months.

Outcome Measure Data

Analysis Population Description

Results were not reported for patients with Extramedullary Disease.

Arm/Group Title	Melphalan Flufenamide (Melflufen) + Dexamethasone: Full Analysis Set	Melphalan Flufenamide (Melflufen) + Dexamethasone: Patients With Triple Class Refractory Disease
Arm/Group Description	Melphalan flufenamide (melflufen) 40 mg Day 1 and dexamethasone 40 mg (reduced dose for patients 75 years or older) on Days 1, 8, 15 and 22 of each 28-day cycle. Melphalan flufenamide (Melflufen) Dexamethasone: IV dexamethasone may be substituted for oral dexamethasone in the US. Oral only in Europe.	Triple class refractory population defined as refractory to or intolerant of at least one immunomodulatory drug, at least one proteasome inhibitor, and at least one anti-CD38 monoclonal antibody
Measure Participants	46	31
Median (Full Range) [months]	1.9	1.9

9. Secondary Outcome

Title	Time to Progression
Description	Duration from start of treatment to first evidence of disease progression as assessed by the investigator. See definitions of response and progression in ORR and PFS outcomes.
Time Frame	From start of treatment to first evidence of disease progression or date of death from any cause, whichever came first. Longest time on study 17 months at data cutoff, 26 patients were still on study.

Outcome Measure Data

Analysis Population Description

Results not reported for patients with Extramedullary Disease.

Arm/Group Title	Melphalan Flufenamide (Melflufen) + Dexamethasone: Full Analysis Set	Melphalan Flufenamide (Melflufen) + Dexamethasone: Patients With Triple Class Refractory Disease
Arm/Group Description	Melphalan flufenamide (melflufen) 40 mg Day 1 and dexamethasone 40 mg (reduced dose for patients 75 years or older) on Days 1, 8, 15 and 22 of each 28-day cycle. Melphalan flufenamide (Melflufen) Dexamethasone	Triple class refractory population defined as refractory to or intolerant of at least one immunomodulatory drug, at least one proteasome inhibitor, and at least one anti-CD38 monoclonal antibody
Measure Participants	157	119
Median (95% Confidence Interval) [months]	4.40	4.07

Adverse Events

Time Frame	Patients were treated in 28 day cycles indefinitely until withdrawal from study, with the longest time on study of 17 months. Adverse events were collected until 30 days after the last dose of study drug. Patients were followed for survival for 24 months after disease progression or start of subsequent anti-myeloma therapy.
Adverse Event Reporting Description	The Safety Analysis Set for evaluation of adverse events included all patients who received at least one dose of melflufen or dexamethasone in the study. Patients that were triple-class refractory and those with extramedullary disease were defined as a subgroups of interest for evaluation.
Arm/Group Title	Melphalan Flufenamide (Melflufen) + Dexamethasone: Full Analysis Set		Melphalan Flufenamide (Melflufen) + Dexamethasone: Patients With Extramedullary Disease		Melphalan Flufenamide (Melflufen) + Dexamethasone: Patients With Triple Class Refractory Disease
Arm/Group Description	Melphalan flufenamide (melflufen) 40 mg Day 1 and dexamethasone 40 mg (reduced dose for patients 75 years or older) on Days 1, 8, 15 and 22 of each 28-day cycle. Melphalan flufenamide (Melflufen) Dexamethasone: IV dexamethasone may be substituted for oral dexamethasone in the US. Oral only in Europe.		Patients with extramedullary disease at baseline defined as myeloma disease either originating in, but extending beyond, the cortical bone or as a separate soft tissue mass.		Triple class refractory population defined as refractory to or intolerant of at least one immunomodulatory drug, at least one proteasome inhibitor, and at least one anti-CD38 monoclonal antibody.
All Cause Mortality
	Melphalan Flufenamide (Melflufen) + Dexamethasone: Full Analysis Set		Melphalan Flufenamide (Melflufen) + Dexamethasone: Patients With Extramedullary Disease		Melphalan Flufenamide (Melflufen) + Dexamethasone: Patients With Triple Class Refractory Disease
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	88/157 (56.1%)		40/55 (72.7%)		72/119 (60.5%)
Serious Adverse Events
	Melphalan Flufenamide (Melflufen) + Dexamethasone: Full Analysis Set		Melphalan Flufenamide (Melflufen) + Dexamethasone: Patients With Extramedullary Disease		Melphalan Flufenamide (Melflufen) + Dexamethasone: Patients With Triple Class Refractory Disease
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	77/157 (49%)		38/55 (69.1%)		61/119 (51.3%)
Blood and lymphatic system disorders
Febrile neutropenia	8/157 (5.1%)		3/55 (5.5%)		6/119 (5%)
Thrombocytopenia	4/157 (2.5%)		2/55 (3.6%)		4/119 (3.4%)
Neutropenia	2/157 (1.3%)		1/55 (1.8%)		2/119 (1.7%)
Anaemia	1/157 (0.6%)		0/55 (0%)		1/119 (0.8%)
Bone marrow failure	1/157 (0.6%)		1/55 (1.8%)		1/119 (0.8%)
Methaemoglobinaemia	1/157 (0.6%)		0/55 (0%)		0/119 (0%)
Sideroblastic anaemia	1/157 (0.6%)		1/55 (1.8%)		1/119 (0.8%)
Cardiac disorders
Atrial fibrillation	1/157 (0.6%)		1/55 (1.8%)		1/119 (0.8%)
Cardiac amyloidosis	1/157 (0.6%)		1/55 (1.8%)		1/119 (0.8%)
Cardiac failure	1/157 (0.6%)		1/55 (1.8%)		1/119 (0.8%)
Cardiopulmonary failure	1/157 (0.6%)		1/55 (1.8%)		1/119 (0.8%)
Gastrointestinal disorders
Lower gastrointestinal haemorrhage	2/157 (1.3%)		0/55 (0%)		1/119 (0.8%)
Abdominal pain	1/157 (0.6%)		1/55 (1.8%)		1/119 (0.8%)
Dysphagia	1/157 (0.6%)		1/55 (1.8%)		1/119 (0.8%)
Haemorrhoidal haemorrhage	1/157 (0.6%)		0/55 (0%)		1/119 (0.8%)
General disorders
General physical health deterioration	4/157 (2.5%)		4/55 (7.3%)		4/119 (3.4%)
Pyrexia	3/157 (1.9%)		1/55 (1.8%)		3/119 (2.5%)
Face oedema	1/157 (0.6%)		1/55 (1.8%)		1/119 (0.8%)
Multiple organ dysfunction syndrome	1/157 (0.6%)		1/55 (1.8%)		1/119 (0.8%)
Hepatobiliary disorders
Cholecystitis	1/157 (0.6%)		1/55 (1.8%)		1/119 (0.8%)
Immune system disorders
Anaphylactic reaction	1/157 (0.6%)		1/55 (1.8%)		0/119 (0%)
Infections and infestations
Pneumonia	14/157 (8.9%)		5/55 (9.1%)		8/119 (6.7%)
Respiratory tract infection	4/157 (2.5%)		1/55 (1.8%)		4/119 (3.4%)
Bronchitis	2/157 (1.3%)		0/55 (0%)		2/119 (1.7%)
Clostridium difficile infection	2/157 (1.3%)		1/55 (1.8%)		2/119 (1.7%)
Influenza	2/157 (1.3%)		2/55 (3.6%)		2/119 (1.7%)
Sepsis	2/157 (1.3%)		1/55 (1.8%)		1/119 (0.8%)
Soft tissue infection	2/157 (1.3%)		0/55 (0%)		2/119 (1.7%)
Upper respiratory tract infection	2/157 (1.3%)		1/55 (1.8%)		0/119 (0%)
Viral upper respiratory tract infection	2/157 (1.3%)		1/55 (1.8%)		2/119 (1.7%)
Abdominal infection	1/157 (0.6%)		0/55 (0%)		0/119 (0%)
Appendicitis	1/157 (0.6%)		0/55 (0%)		0/119 (0%)
Bacterial sepsis	1/157 (0.6%)		0/55 (0%)		1/119 (0.8%)
Bronchiolitis	1/157 (0.6%)		1/55 (1.8%)		1/119 (0.8%)
Bronchitis viral	1/157 (0.6%)		0/55 (0%)		1/119 (0.8%)
Cellulitis	1/157 (0.6%)		1/55 (1.8%)		1/119 (0.8%)
Diverticulitis	1/157 (0.6%)		0/55 (0%)		0/119 (0%)
Escherichia sepsis	1/157 (0.6%)		0/55 (0%)		1/119 (0.8%)
Fungal sepsis	1/157 (0.6%)		0/55 (0%)		1/119 (0.8%)
Gastroenteritis	1/157 (0.6%)		0/55 (0%)		1/119 (0.8%)
Lower respiratory infection	1/157 (0.6%)		0/55 (0%)		1/119 (0.8%)
Pneumocystis jirovecii pneumonia	1/157 (0.6%)		0/55 (0%)		1/119 (0.8%)
Pneumonia viral	1/157 (0.6%)		1/55 (1.8%)		1/119 (0.8%)
Respiratory tract infection viral	1/157 (0.6%)		0/55 (0%)		1/119 (0.8%)
Sinusitis	1/157 (0.6%)		0/55 (0%)		1/119 (0.8%)
Urosepsis	1/157 (0.6%)		1/55 (1.8%)		1/119 (0.8%)
Viral infection	1/157 (0.6%)		0/55 (0%)		1/119 (0.8%)
Injury, poisoning and procedural complications
Femur fracture	2/157 (1.3%)		2/55 (3.6%)		2/119 (1.7%)
Fall	1/157 (0.6%)		1/55 (1.8%)		1/119 (0.8%)
Investigations
Platelet count decreased	4/157 (2.5%)		2/55 (3.6%)		4/119 (3.4%)
Neutrophil count decreased	1/157 (0.6%)		0/55 (0%)		1/119 (0.8%)
Metabolism and nutrition disorders
Hypercalcaemia	4/157 (2.5%)		3/55 (5.5%)		4/119 (3.4%)
Failure to thrive	1/157 (0.6%)		1/55 (1.8%)		1/119 (0.8%)
Metabolic disorder	1/157 (0.6%)		1/55 (1.8%)		1/119 (0.8%)
Musculoskeletal and connective tissue disorders
Bone pain	2/157 (1.3%)		0/55 (0%)		2/119 (1.7%)
Back pain	1/157 (0.6%)		0/55 (0%)		0/119 (0%)
Pain in extremity	1/157 (0.6%)		1/55 (1.8%)		1/119 (0.8%)
Pathological fracture	1/157 (0.6%)		1/55 (1.8%)		1/119 (0.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma	2/157 (1.3%)		1/55 (1.8%)		1/119 (0.8%)
Basal cell carcinoma	1/157 (0.6%)		0/55 (0%)		1/119 (0.8%)
Malignant melanoma	1/157 (0.6%)		0/55 (0%)		1/119 (0.8%)
Plasma cell leukaemia	1/157 (0.6%)		1/55 (1.8%)		1/119 (0.8%)
Plasma cell myeloma	1/157 (0.6%)		1/55 (1.8%)		1/119 (0.8%)
Nervous system disorders
Encephalopathy	1/157 (0.6%)		1/55 (1.8%)		1/119 (0.8%)
Extradural haematoma	1/157 (0.6%)		1/55 (1.8%)		1/119 (0.8%)
Hyperammonaemic encephalopathy	1/157 (0.6%)		1/55 (1.8%)		1/119 (0.8%)
Renal and urinary disorders
Acute kidney injury	4/157 (2.5%)		2/55 (3.6%)		4/119 (3.4%)
Nephropathy	1/157 (0.6%)		1/55 (1.8%)		1/119 (0.8%)
Urinary retention	1/157 (0.6%)		1/55 (1.8%)		1/119 (0.8%)
Respiratory, thoracic and mediastinal disorders
Diffuse alveolar damage	1/157 (0.6%)		0/55 (0%)		1/119 (0.8%)
Dysphonia	1/157 (0.6%)		1/55 (1.8%)		1/119 (0.8%)
Epistaxis	1/157 (0.6%)		1/55 (1.8%)		1/119 (0.8%)
Pulmonary oedema	1/157 (0.6%)		1/55 (1.8%)		1/119 (0.8%)
Dyspnoea	2/157 (1.3%)		2/55 (3.6%)		2/119 (1.7%)
Pleural effusion	2/157 (1.3%)		2/55 (3.6%)		2/119 (1.7%)
Respiratory failure	2/157 (1.3%)		1/55 (1.8%)		0/119 (0%)
Vascular disorders
Hypotension	2/157 (1.3%)		2/55 (3.6%)		2/119 (1.7%)
Deep vein thrombosis	1/157 (0.6%)		1/55 (1.8%)		1/119 (0.8%)
Other (Not Including Serious) Adverse Events
	Melphalan Flufenamide (Melflufen) + Dexamethasone: Full Analysis Set		Melphalan Flufenamide (Melflufen) + Dexamethasone: Patients With Extramedullary Disease		Melphalan Flufenamide (Melflufen) + Dexamethasone: Patients With Triple Class Refractory Disease
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	157/157 (100%)		55/55 (100%)		119/119 (100%)
Blood and lymphatic system disorders
Anaemia	111/157 (70.7%)		33/55 (60%)		77/119 (64.7%)
Thrombocytopenia	94/157 (59.9%)		26/55 (47.3%)		65/119 (54.6%)
Neutropenia	87/157 (55.4%)		23/55 (41.8%)		61/119 (51.3%)
Leukopenia	12/157 (7.6%)		3/55 (5.5%)		9/119 (7.6%)
Febrile neutropenia	10/157 (6.4%)		4/55 (7.3%)		7/119 (5.9%)
Lymphopenia	8/157 (5.1%)		3/55 (5.5%)		6/119 (5%)
Cardiac disorders
Tachycardia	8/157 (5.1%)		6/55 (10.9%)		7/119 (5.9%)
Gastrointestinal disorders
Nausea	50/157 (31.8%)		16/55 (29.1%)		38/119 (31.9%)
Diarrhoea	42/157 (26.8%)		14/55 (25.5%)		27/119 (22.7%)
Constipation	23/157 (14.6%)		11/55 (20%)		19/119 (16%)
Vomiting	21/157 (13.4%)		10/55 (18.2%)		19/119 (16%)
Abdominal pain	8/157 (5.1%)		4/55 (7.3%)		5/119 (4.2%)
General disorders
Fatigue	46/157 (29.3%)		14/55 (25.5%)		35/119 (29.4%)
Asthenia	42/157 (26.8%)		10/55 (18.2%)		28/119 (23.5%)
Pyrexia	38/157 (24.2%)		10/55 (18.2%)		29/119 (24.4%)
Oedema peripheral	22/157 (14%)		9/55 (16.4%)		11/119 (9.2%)
Infections and infestations
Upper respiratory tract infection	25/157 (15.9%)		13/55 (23.6%)		18/119 (15.1%)
Pneumonia	20/157 (12.7%)		8/55 (14.5%)		14/119 (11.8%)
Respiratory tract infection	10/157 (6.4%)		2/55 (3.6%)		8/119 (6.7%)
Bronchitis	8/157 (5.1%)		1/55 (1.8%)		6/119 (5%)
Injury, poisoning and procedural complications
Contusion	8/157 (5.1%)		3/55 (5.5%)		6/119 (5%)
Investigations
White blood cell count decreased	44/157 (28%)		19/55 (34.5%)		35/119 (29.4%)
Neutrophil count decreased	41/157 (26.1%)		19/55 (34.5%)		33/119 (27.7%)
Platelet count decreased	36/157 (22.9%)		17/55 (30.9%)		31/119 (26.1%)
Blood creatinine increased	9/157 (5.7%)		1/55 (1.8%)		7/119 (5.9%)
Metabolism and nutrition disorders
Decreased appetite	22/157 (14%)		6/55 (10.9%)		13/119 (10.9%)
Hypokalaemia	22/157 (14%)		9/55 (16.4%)		15/119 (12.6%)
Hypocalcaemia	16/157 (10.2%)		6/55 (10.9%)		10/119 (8.4%)
Hypomagnesaemia	15/157 (9.6%)		7/55 (12.7%)		11/119 (9.2%)
Hypophosphataemia	13/157 (8.3%)		6/55 (10.9%)		9/119 (7.6%)
Hyperglycaemia	8/157 (5.1%)		1/55 (1.8%)		4/119 (3.4%)
Musculoskeletal and connective tissue disorders
Bone pain	20/157 (12.7%)		7/55 (12.7%)		16/119 (13.4%)
Pain in extremity	20/157 (12.7%)		10/55 (18.2%)		17/119 (14.3%)
Back pain	19/157 (12.1%)		6/55 (10.9%)		11/119 (9.2%)
Arthralgia	16/157 (10.2%)		6/55 (10.9%)		11/119 (9.2%)
Musculoskeletal chest pain	10/157 (6.4%)		4/55 (7.3%)		6/119 (5%)
Myalgia	9/157 (5.7%)		6/55 (10.9%)		8/119 (6.7%)
Musculoskeletal pain	8/157 (5.1%)		4/55 (7.3%)		7/119 (5.9%)
Nervous system disorders
Headache	21/157 (13.4%)		6/55 (10.9%)		17/119 (14.3%)
Dizziness	17/157 (10.8%)		1/55 (1.8%)		8/119 (6.7%)
Psychiatric disorders
Insomnia	18/157 (11.5%)		4/55 (7.3%)		12/119 (10.1%)
Respiratory, thoracic and mediastinal disorders
Cough	26/157 (16.6%)		6/55 (10.9%)		19/119 (16%)
Dyspnoea	17/157 (10.8%)		5/55 (9.1%)		13/119 (10.9%)
Dyspnoea exertional	16/157 (10.2%)		7/55 (12.7%)		11/119 (9.2%)
Epistaxis	14/157 (8.9%)		7/55 (12.7%)		12/119 (10.1%)
Vascular disorders
Hypotension	8/157 (5.1%)		4/55 (7.3%)		7/119 (5.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.