Glembatumumab Vedotin in Treating Patients With Recurrent or Refractory Osteosarcoma

• ClinicalTrials.gov Identifier: NCT02487979
• Recruitment Status: Completed
• First Posted: July 2, 2015
• Results First Posted: October 15, 2018
• Last Update Posted: January 18, 2022
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Recurrent Osteosarcoma
• Interventions: Drug: Glembatumumab Vedotin; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study
• Enrollment: 22

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Treatment (Glembatumumab Vedotin)
Arm/Group Description	Patients receive glembatumumab vedotin IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. Glembatumumab Vedotin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Period Title: Overall Study
Started	22
Completed	1
Not Completed	21
Reason Not Completed
Physician Decision	2
Withdrawal by Subject	2
Progressive Disease	17

Baseline Characteristics

Arm/Group Title		Treatment (Glembatumumab Vedotin)
Arm/Group Description		Patients receive glembatumumab vedotin IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. Glembatumumab Vedotin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Overall Number of Baseline Participants		22
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	22 participants
		20.09 (5.30)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	22 participants
	Female	7 31.8%
	Male	15 68.2%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	22 participants
	Hispanic or Latino	3 13.6%
	Not Hispanic or Latino	19 86.4%
	Unknown or Not Reported	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	22 participants
	American Indian or Alaska Native	0 0.0%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	2 9.1%
	White	20 90.9%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	22 participants
Canada		1
United States		21

Outcome Measures

1. Primary Outcome

Title	Disease Control Success
Description	The number of patients who do not experience disease progression or death in the six cycles following enrollment on AOST1521
Time Frame	First six cycles (21-day cycle) of protocol therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Glembatumumab Vedotin)
Arm/Group Description:	Patients receive glembatumumab vedotin IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. Glembatumumab Vedotin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Overall Number of Participants Analyzed	22
Measure Type: Count of Participants; Unit of Measure: Participants
	3 13.6%

2. Secondary Outcome

Title	Toxicity Associated With Chemotherapy
Description	The number of cycles aggregated across all patients where CTC Version 4 grade 3 or higher.
Time Frame	Duration of protocol therapy - Up to two years

Outcome Measure Data

Analysis Population Description

22 patients were treated on protocol therapy. Sixty-one (61) cycles were reported for the analysis of toxicity.

Arm/Group Title	Treatment (Glembatumumab Vedotin)
Arm/Group Description:	Patients receive glembatumumab vedotin IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. Glembatumumab Vedotin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Overall Number of Participants Analyzed	22
Measure Type: Number; Unit of Measure: cycles
Incidence of Abdominal Pain	2
Incidence of acneiform rash	1
Incidence of Anaphylaxis	1
Incidence of Anemia	2
Incidence of Anorexia	1
Incidence of Back Pain	2
Incidence of Constipation	1
Incidence of Febrile Neutropenia	1
Incidence of Headache	1
Incidence of Hypertension	1
Incidence of Hypocalcemia	1
Incidence of Hypokalemia	4
Incidence of Hypophosphatemia	2
Incidence of Hypotension	1
Incidence of Leukopenia	1
Incidence of Lymphopenia	1
Incidence of Mucocitis	2
Incidence of Myalgia	1
Incidence of Nausea	1
Incidence of Neutropenia	2
Incidence of Pain	2
Incidence of Pneumothorax	1
Incidence of Thrombocytopenia	1

3. Secondary Outcome

Title	Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Half-life
Description	Total antibody and antibody-drug conjugate half-life are estimated from the sampling time points: Before first dose (Baseline), end of infusion, at 1, 2, 4, and 24 hours post infusion
Time Frame	Baseline to 24 hours post infusion on course 1

Outcome Measure Data

Analysis Population Description

Samples were provided for four patients

Arm/Group Title	Treatment (Glembatumumab Vedotin)
Arm/Group Description:	Patients receive glembatumumab vedotin IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. Glembatumumab Vedotin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Overall Number of Participants Analyzed	4
Mean (Standard Deviation); Unit of Measure: hours
Total antibody half-life	35.2 (6.4)
Antibody-Drug Conjugate half-life	29.1 (8.4)

4. Secondary Outcome

Title	Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Clearance
Description	Total antibody and antibody-drug conjugate clearance are estimated from the sampling time points: Before first dose (Baseline), end of infusion, at 1, 2, 4, and 24 hours post infusion
Time Frame	Baseline to 24 hours post infusion on course 1

Outcome Measure Data

Analysis Population Description

Samples were provided for four patients

Arm/Group Title	Treatment (Glembatumumab Vedotin)
Arm/Group Description:	Patients receive glembatumumab vedotin IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. Glembatumumab Vedotin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Overall Number of Participants Analyzed	4
Mean (Standard Deviation); Unit of Measure: millilitres per hour per kilogram
Total antibody clearance	0.8 (0.1)
Antibody-Drug Conjugate clearance	0.9 (0.3)

5. Secondary Outcome

Title	Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Areas Under the Curve
Description	Total antibody and antibody-drug conjugate areas under the curve are estimated from the sampling time points: Before first dose (Baseline), end of infusion, at 1, 2, 4, and 24 hours post infusion
Time Frame	Baseline to 24 hours post infusion on course 1

Outcome Measure Data

Analysis Population Description

Samples were provided for four patients

Arm/Group Title	Treatment (Glembatumumab Vedotin)
Arm/Group Description:	Patients receive glembatumumab vedotin IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. Glembatumumab Vedotin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Overall Number of Participants Analyzed	4
Mean (Standard Deviation); Unit of Measure: hour-microgram per millilitre
Total antibody area under the curve	2320.0 (342)
Antibody-Drug Conjugate area under the curve	2259.5 (749.6)

6. Secondary Outcome

Title	Number of Participants With Glycoprotein NMB (GPNMB) Expression Stratified by Immunohistochemistry (IHC) Staining Strength
Description	GPNMB expression by IHC of 0+ to 3+ staining strength as assessed on archived tumor specimens. 0 being no GPNMB expression and 3 indicating strong GPNMB expression.
Time Frame	Prior to the time of enrollment

Outcome Measure Data

Analysis Population Description

Analysis was successfully completed for 19 patients

Arm/Group Title	Treatment (Glembatumumab Vedotin)
Arm/Group Description:	Patients receive glembatumumab vedotin IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. Glembatumumab Vedotin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Overall Number of Participants Analyzed	19
Measure Type: Count of Participants; Unit of Measure: Participants
0+ staining strength	1 5.3%
1+ staining strength	3 15.8%
2+ staining strength	2 10.5%
3+ staining strength	13 68.4%

7. Secondary Outcome

Title	RECIST Response
Description	The number of patients who experience a complete or partial response according the RECIST criteria for target lesions complete response (CR) disappearance of all lesions; partial response (PR ) >= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR+PR.
Time Frame	First six cycles (21-day cycle) of protocol therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Glembatumumab Vedotin)
Arm/Group Description:	Patients receive glembatumumab vedotin IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. Glembatumumab Vedotin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Overall Number of Participants Analyzed	22
Measure Type: Count of Participants; Unit of Measure: Participants
	1 4.5%

Adverse Events

Time Frame	Overall protocol therapy up to 14 months in total or 18 cycles, whichever occurs first.
Adverse Event Reporting Description	Adverse event reporting is collected routinely using case report forms. SAE field contains NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients are excluded from reporting of adverse events.
Arm/Group Title	Treatment (Glembatumumab Vedotin)
Arm/Group Description	Patients receive glembatumumab vedotin IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. Glembatumumab Vedotin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
All-Cause Mortality
	Treatment (Glembatumumab Vedotin)
	Affected / at Risk (%)
Total	14/22 (63.64%)
Serious Adverse Events
	Treatment (Glembatumumab Vedotin)
	Affected / at Risk (%)	# Events
Total	8/22 (36.36%)
Blood and lymphatic system disorders
Anemia †	2/22 (9.09%)	2
Febrile neutropenia †	1/22 (4.55%)	1
Gastrointestinal disorders
Abdominal pain †	1/22 (4.55%)	1
Constipation †	1/22 (4.55%)	1
Mucositis oral †	1/22 (4.55%)	1
Nausea †	1/22 (4.55%)	1
Vomiting †	1/22 (4.55%)	1
General disorders
Fever †	1/22 (4.55%)	1
Pain †	1/22 (4.55%)	1
Immune system disorders
Anaphylaxis †	1/22 (4.55%)	1
Investigations
Neutrophil count decreased †	1/22 (4.55%)	1
Platelet count decreased †	1/22 (4.55%)	1
White blood cell decreased †	1/22 (4.55%)	1
Metabolism and nutrition disorders
Acidosis †	1/22 (4.55%)	1
Hypocalcemia †	1/22 (4.55%)	1
Hypokalemia †	2/22 (9.09%)	2
Hypophosphatemia †	1/22 (4.55%)	1
Musculoskeletal and connective tissue disorders
Back pain †	2/22 (9.09%)	2
Myalgia †	1/22 (4.55%)	1
Pain in extremity †	1/22 (4.55%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify †	1/22 (4.55%)	1
Nervous system disorders
Headache †	1/22 (4.55%)	1
Peripheral sensory neuropathy †	1/22 (4.55%)	1
Renal and urinary disorders
Acute kidney injury †	1/22 (4.55%)	1
Respiratory, thoracic and mediastinal disorders
Pneumothorax †	1/22 (4.55%)	1
Respiratory failure †	1/22 (4.55%)	1
Skin and subcutaneous tissue disorders
Rash maculo-papular †	3/22 (13.64%)	3
Vascular disorders
Hypotension †	1/22 (4.55%)	1
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Treatment (Glembatumumab Vedotin)
	Affected / at Risk (%)	# Events
Total	7/22 (31.82%)
Gastrointestinal disorders
Mucositis oral †	1/22 (4.55%)	1
Nausea †	1/22 (4.55%)	1
General disorders
Pain †	1/22 (4.55%)	1
Infections and infestations
Infections and infestations - Other, specify †	1/22 (4.55%)	1
Investigations
Lymphocyte count decreased †	1/22 (4.55%)	1
Neutrophil count decreased †	1/22 (4.55%)	1
Metabolism and nutrition disorders
Anorexia †	1/22 (4.55%)	1
Hypokalemia †	1/22 (4.55%)	1
Hypophosphatemia †	1/22 (4.55%)	1
Nervous system disorders
Somnolence †	1/22 (4.55%)	1
Skin and subcutaneous tissue disorders
Rash acneiform †	1/22 (4.55%)	1
Rash maculo-papular †	2/22 (9.09%)	2
Vascular disorders
Hypertension †	1/22 (4.55%)	1
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS 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.

Results Point of Contact

• Name/Title: Results Reporting Coordinator
• Organization: Children's Oncology Group
• Phone: 626-447-0064
• EMail: resultsreportingcoordinator@childrensoncologygroup.org

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kopp LM, Malempati S, Krailo M, Gao Y, Buxton A, Weigel BJ, Hawthorne T, Crowley E, Moscow JA, Reid JM, Villalobos V, Randall RL, Gorlick R, Janeway KA. Phase II trial of the glycoprotein non-metastatic B-targeted antibody-drug conjugate, glembatumumab vedotin (CDX-011), in recurrent osteosarcoma AOST1521: A report from the Children's Oncology Group. Eur J Cancer. 2019 Nov;121:177-183. doi: 10.1016/j.ejca.2019.08.015. Epub 2019 Oct 3.

Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14. Review.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT02487979
• Other Study ID Numbers: NCI-2015-01037; NCI-2015-01037 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); AOST1521; s16-01136; AOST1521 ( Other Identifier: Children's Oncology Group ); AOST1521 ( Other Identifier: CTEP ); U10CA180886 ( U.S. NIH Grant/Contract )
• First Submitted: July 1, 2015
• First Posted: July 2, 2015
• Results First Submitted: August 3, 2018
• Results First Posted: October 15, 2018
• Last Update Posted: January 18, 2022