An Open-label Extension Study of PSMA ADC 2301 in mCRPC

• Sponsor: Progenics Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02020135
• Collaborator: (none)
• Enrollment: 9
• Locations: 6
• Arm: 1
• Duration (Months): 17
• Patients Per Site: 1.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

PSMA ADC 2301EXT is an open-label study to further assess the anti-tumor activity as measured by radiographic imaging and biomarkers, safety and tolerability of Prostate Specific Membrane Antigen Antibody Drug Conjugate (PSMA ADC) in subjects with mCRPC. Subjects who have participated in the PSMA ADC 2301 study and who, in the opinion of the Principal Investigator are likely to benefit from continued treatment with PSMA ADC are eligible for the PSMA ADC 2301 extension study. Subjects who are benefiting from treatment may be able to receive up to an additional eight to sixteen doses (every 3 weeks) of PSMA ADC.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: PSMA ADC	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label Treatment Extension of PSMA ADC in Subjects With Metastatic Castration-resistant Prostate Cancer (mCRPC)
• Study Start Date: Oct 1, 2013
• Actual Primary Completion Date: Feb 1, 2015
• Actual Study Completion Date: Mar 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1: PSMA ADC Subjects started the extension study at the same dose received upon completion of the core PSMA ADC 2301 study. Each Prostate Specific Membrane Antigen Antibody Drug Conjugate (PSMA ADC) dose was administered as an IV infusion over approximately 60 minutes once every three weeks (Q3W) for up to eight doses, unless a dose delay or dose reduction was required.	Drug: PSMA ADC; Upon recommendation from the PI and after Sponsor approval, a subject benefiting from treatment could have received up to eight additional doses Q3W. Subjects were weighed prior to each cycle and dosing was calculated on a mg/kg basis prior to each dose, with a maximum weight of 100 kg for dosing calculations.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Total Serum PSA Response [25 Weeks]

   Total serum PSA (prostate-specific antigen) was measured at baseline and had at least one post-baseline assessment. PSA response was examined at two levels: at least 30% decrease or at least 50% decrease in serum PSA. Response was assessed as the maximum decrease over the extension study. Response was defined as any decrease from baseline of at least 30% or 50%.

2. CTC Response [25 weeks]

   Circulating tumor cells (CTC) response was measured at baseline and had at least one post-baseline assessment. Response was assessed as the maximum decrease over the extension study. Response was defined as any decrease from baseline of at least 50%.

3. Overall Radiologic Response [25 weeks]

   Overall radiologic response was measured at baseline and post-baseline. Imaging techniques used at screening were used throughout the study. The preferred imaging techniques include: bone scan, contrast enhanced CT of chest, contrast enhanced CT of pelvis, and contrast enhanced CT of upper & lower abdomen. Best overall radiologic response (confirmed), target and non-target lesions, was defined as responses in bone, visceral or nodal metastases according to the Modified Response Evaluation Criteria (RECIST 1.1). The best overall radiologic response is the best response recorded from the start of the treatment until disease progression/recurrence (taking, as reference for progressive disease, the smallest measurements recorded since the treatment started). The subject's best response assignment depended on the achievement of both measurement and confirmation criteria.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Subjects who have completed the PSMA ADC 2301 study and who, in the opinion of the investigator, are likely to benefit from continued treatment with PSMA ADC

2. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

3. If chemically castrated, subjects must agree to stay on androgen-deprivation therapy for the duration of the study

4. If applicable, men must agree to commit to the use of a medically acceptable method of birth control (e.g., spermicide in conjunction with a barrier such as a condom) or sexual abstinence for the duration of the study, including 30 days after the last dose of study drug

Exclusion Criteria:

1. An acute infection requiring ongoing antibiotic therapy (e.g., UTI, indwelling catheter or other potential site(s) of infection)

2. History of significant hypersensitivity reactions to PSMA ADC or any of its components, or to any prior investigational or approved monoclonal antibodies (mAbs), immunoglobulin (Ig) fusion proteins (e.g., circulating neutralizing antibodies), or ADC

3. Clinically significant cardiac disease or severe debilitating pulmonary disease

4. Any recent or ongoing medical condition that may interfere with a subject's participation or compliance with the study or evaluation of PSMA ADC

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Tucson	Arizona	United States
2		New Orleans	Louisiana	United States	70112
3		Baltimore	Maryland	United States	21201
4		Las Vegas	Nevada	United States	89169
5		Stony Brook	New York	United States	11794
6		Myrtle Beach	South Carolina	United States	29572

Sponsors and Collaborators

• Progenics Pharmaceuticals, Inc.

Investigators

• Study Director: Vivien Wong, PhD, Progenics Pharmaceuticals, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Progenics Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT02020135
• Other Study ID Numbers: PSMA ADC 2301EXT
• First Posted: Dec 24, 2013
• Last Update Posted: Mar 24, 2017
• Last Verified: Feb 1, 2017

• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Arm/Group Title	Arm 1: PSMA ADC
Arm/Group Description	Subjects started the extension study at the same dose received upon completion of the core PSMA ADC 2301 study. Each PSMA ADC dose was administered as an IV infusion over approximately 60 minutes once every three weeks (Q3W) for up to eight doses, unless a dose delay or dose reduction was required. PSMA ADC: Upon recommendation from the PI and after Sponsor approval, a subject benefitting from treatment could have received up to eight additional doses Q3W. Subjects were weighed prior to each cycle and dosing was calculated on a mg/kg basis prior to each dose, with a maximum weight of 100 kg for dosing calculations.
Period Title: Overall Study
STARTED	9
COMPLETED	0
NOT COMPLETED	9

Baseline Characteristics

Arm/Group Title	PSMA ADC Chemotherapy-experienced	PSMA ADC Chemotherapy-naive	Total
Arm/Group Description	Subjects started the extension study at the same dose received upon completion of the core PSMA ADC 2301 study. Each Prostate Specific Membrane Antigen Antibody Drug Conjugate (PSMA ADC) dose was administered as an IV infusion over approximately 60 minutes once every three weeks (Q3W) for up to eight doses, unless a dose delay or dose reduction was required. PSMA ADC: Upon recommendation from the PI and after Sponsor approval, a subject benefitting from treatment could have received up to eight additional doses Q3W. Subjects were weighed prior to each cycle and dosing was calculated on a mg/kg basis prior to each dose, with a maximum weight of 100 kg for dosing calculations.	Subjects started the extension study at the same dose received upon completion of the core PSMA ADC 2301 study. Each Prostate Specific Membrane Antigen Antibody Drug Conjugate (PSMA ADC) dose was administered as an IV infusion over approximately 60 minutes once every three weeks (Q3W) for up to eight doses, unless a dose delay or dose reduction was required. PSMA ADC: Upon recommendation from the PI and after Sponsor approval, a subject benefitting from treatment could have received up to eight additional doses Q3W. Subjects were weighed prior to each cycle and dosing was calculated on a mg/kg basis prior to each dose, with a maximum weight of 100 kg for dosing calculations.	Total of all reporting groups
Overall Participants	6	3	9
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	73.2	77.3	74.6
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	6 100%	3 100%	9 100%
Prostate specific antigen (PSA) (ug/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ug/mL]	1446.3 (2209.9)	91.3 (125.8)	994.6 (1874.9)
PSA (ug/mL) [Median (Full Range) ]
Median (Full Range) [ug/mL]	442.2	32.1	221.2

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Total Serum PSA Response
Description	Total serum PSA (prostate-specific antigen) was measured at baseline and had at least one post-baseline assessment. PSA response was examined at two levels: at least 30% decrease or at least 50% decrease in serum PSA. Response was assessed as the maximum decrease over the extension study. Response was defined as any decrease from baseline of at least 30% or 50%.
Time Frame	25 Weeks

Outcome Measure Data

Analysis Population Description

Both groups must also have received and progressed on abiraterone acetate and/or enzalutamide prior to the study (once these agents were commercially available for use). The population examined was those subjects with a PSA baseline value and at least one post-baseline value.

Arm/Group Title	PSMA ADC Chemotherapy-experienced	PSMA ADC Chemotherapy-naive
Arm/Group Description	The chemotherapy-experienced group was comprised of 6 subjects who must have received at least one taxane-containing chemotherapy regimen (e.g., docetaxel, cabazitaxel) prior to the study (more than two cytotoxic chemotherapy regimens required sponsor approval for study participation). Subjects started the extension study at the same dose received upon completion of the core PSMA ADC 2301 study. Each PSMA ADC dose was administered as an IV infusion over approximately 60 minutes once every three weeks (Q3W) for up to eight doses, unless a dose delay or dose reduction was required.	The chemotherapy-naïve group was comprised of 3 subjects who were cytotoxic chemotherapy-naïve. Chemotherapy-naïve subjects must have received and progressed on Radium-223 (following its approval by FDA), or have been ineligible for it, refused it, had an intolerance to it, or did not have access to it. Subjects started the extension study at the same dose received upon completion of the core PSMA ADC 2301 study. Each PSMA ADC dose was administered as an IV infusion over approximately 60 minutes once every three weeks (Q3W) for up to eight doses, unless a dose delay or dose reduction was required.
Measure Participants	6	3
>30% Decrease in PSA	67	33
>50% Decrease in PSA	33	0

2. Primary Outcome

Title	CTC Response
Description	Circulating tumor cells (CTC) response was measured at baseline and had at least one post-baseline assessment. Response was assessed as the maximum decrease over the extension study. Response was defined as any decrease from baseline of at least 50%.
Time Frame	25 weeks

Outcome Measure Data

Analysis Population Description

Both groups must also have received and progressed on abiraterone acetate and/or enzalutamide prior to the study (once these agents were commercially available for use). The population examined was those subjects with a CTC baseline value and at least one post-baseline value.

Arm/Group Title	PSMA ADC Chemotherapy-experienced	PSMA ADC Chemotherapy-naive
Arm/Group Description	The chemotherapy-experienced group was comprised of 6 subjects who must have received at least one taxane-containing chemotherapy regimen (e.g., docetaxel, cabazitaxel) prior to the study (more than two cytotoxic chemotherapy regimens required sponsor approval for study participation). Subjects started the extension study at the same dose received upon completion of the core PSMA ADC 2301 study. Each PSMA ADC dose was administered as an IV infusion over approximately 60 minutes once every three weeks (Q3W) for up to eight doses, unless a dose delay or dose reduction was required.	The chemotherapy-naïve group was comprised of 3 subjects who were cytotoxic chemotherapy-naïve. Chemotherapy-naïve subjects must have received and progressed on Radium-223 (following its approval by FDA), or have been ineligible for it, refused it, had an intolerance to it, or did not have access to it. Subjects started the extension study at the same dose received upon completion of the core PSMA ADC 2301 study. Each PSMA ADC dose was administered as an IV infusion over approximately 60 minutes once every three weeks (Q3W) for up to eight doses, unless a dose delay or dose reduction was required.
Measure Participants	5	2
Number [% of responders]	100	50

3. Primary Outcome

Title	Overall Radiologic Response
Description	Overall radiologic response was measured at baseline and post-baseline. Imaging techniques used at screening were used throughout the study. The preferred imaging techniques include: bone scan, contrast enhanced CT of chest, contrast enhanced CT of pelvis, and contrast enhanced CT of upper & lower abdomen. Best overall radiologic response (confirmed), target and non-target lesions, was defined as responses in bone, visceral or nodal metastases according to the Modified Response Evaluation Criteria (RECIST 1.1). The best overall radiologic response is the best response recorded from the start of the treatment until disease progression/recurrence (taking, as reference for progressive disease, the smallest measurements recorded since the treatment started). The subject's best response assignment depended on the achievement of both measurement and confirmation criteria.
Time Frame	25 weeks

Outcome Measure Data

Analysis Population Description

Both groups must also have received and progressed on abiraterone acetate and/or enzalutamide prior to the study (once these agents were commercially available for use). All subjects (n=9) enrolled in 2301EXT were evaluated.

Arm/Group Title	PSMA ADC Chemotherapy-experienced	PSMA ADC Chemotherapy-naive
Arm/Group Description	The chemotherapy-experienced group was comprised of 6 subjects who must have received at least one taxane-containing chemotherapy regimen (e.g., docetaxel, cabazitaxel) prior to the study (more than two cytotoxic chemotherapy regimens required sponsor approval for study participation). Subjects started the extension study at the same dose received upon completion of the core PSMA ADC 2301 study. Each PSMA ADC dose was administered as an IV infusion over approximately 60 minutes once every three weeks (Q3W) for up to eight doses, unless a dose delay or dose reduction was required.	The chemotherapy-naïve group was comprised of 3 subjects who were cytotoxic chemotherapy-naïve. Chemotherapy-naïve subjects must have received and progressed on Radium-223 (following its approval by FDA), or have been ineligible for it, refused it, had an intolerance to it, or did not have access to it. Subjects started the extension study at the same dose received upon completion of the core PSMA ADC 2301 study. Each PSMA ADC dose was administered as an IV infusion over approximately 60 minutes once every three weeks (Q3W) for up to eight doses, unless a dose delay or dose reduction was required.
Measure Participants	6	3
Partial response	17	0
Stable disease	83	100

Adverse Events

Time Frame	25 weeks
Arm/Group Title	PSMA ADC Chemotherapy-experienced		PSMA ADC Chemotherapy-naive
Arm/Group Description	The chemotherapy-experienced group was comprised of 6 subjects who must have received at least one taxane-containing chemotherapy regimen (e.g., docetaxel, cabazitaxel) prior to the study (more than two cytotoxic chemotherapy regimens required sponsor approval for study participation). Subjects started the extension study at the same dose received upon completion of the core PSMA ADC 2301 study. Each PSMA ADC dose was administered as an IV infusion over approximately 60 minutes once every three weeks (Q3W) for up to eight doses, unless a dose delay or dose reduction was required.		The chemotherapy-naïve group was comprised of 3 subjects who were cytotoxic chemotherapy-naïve. Chemotherapy-naïve subjects must have received and progressed on Radium-223 (following its approval by FDA), or have been ineligible for it, refused it, had an intolerance to it, or did not have access to it. Subjects started the extension study at the same dose received upon completion of the core PSMA ADC 2301 study. Each PSMA ADC dose was administered as an IV infusion over approximately 60 minutes once every three weeks (Q3W) for up to eight doses, unless a dose delay or dose reduction was required.
All Cause Mortality
	PSMA ADC Chemotherapy-experienced		PSMA ADC Chemotherapy-naive
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	PSMA ADC Chemotherapy-experienced		PSMA ADC Chemotherapy-naive
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)		0/3 (0%)
Cardiac disorders
Tachycardia	1/6 (16.7%)		0/3 (0%)
Infections and infestations
Pneumonia	1/6 (16.7%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	PSMA ADC Chemotherapy-experienced		PSMA ADC Chemotherapy-naive
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		3/3 (100%)
Blood and lymphatic system disorders
Anemia	1/6 (16.7%)		0/3 (0%)
Neutropenia	0/6 (0%)		1/3 (33.3%)
Cardiac disorders
Arrythmia	1/6 (16.7%)		0/3 (0%)
Bradycardia	1/6 (16.7%)		0/3 (0%)
Tachycardia	1/6 (16.7%)		0/3 (0%)
Eye disorders
Vision blurred	0/6 (0%)		1/3 (33.3%)
Gastrointestinal disorders
Constipation	1/6 (16.7%)		1/3 (33.3%)
Nausea	0/6 (0%)		2/3 (66.7%)
Vomiting	0/6 (0%)		1/3 (33.3%)
General disorders
Asthenia	1/6 (16.7%)		0/3 (0%)
Fatigue	2/6 (33.3%)		1/3 (33.3%)
Gait disturbance	1/6 (16.7%)		1/3 (33.3%)
Gravitational edema	1/6 (16.7%)		0/3 (0%)
Chills	0/6 (0%)		1/3 (33.3%)
Peripheral edema	1/6 (16.7%)		1/3 (33.3%)
Pain	1/6 (16.7%)		0/3 (0%)
Pyrexia	1/6 (16.7%)		0/3 (0%)
Infections and infestations
Diverticulitis	0/6 (0%)		1/3 (33.3%)
Pneumonia	1/6 (16.7%)		0/3 (0%)
Injury, poisoning and procedural complications
Fall	1/6 (16.7%)		0/3 (0%)
Investigations
Blood creatinine increased	0/6 (0%)		1/3 (33.3%)
Blood urea increased	0/6 (0%)		1/3 (33.3%)
Weight decreased	1/6 (16.7%)		0/3 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/6 (16.7%)		0/3 (0%)
Back pain	1/6 (16.7%)		0/3 (0%)
Muscle spasms	1/6 (16.7%)		0/3 (0%)
Muscular weakness	1/6 (16.7%)		1/3 (33.3%)
Pain in extremity	2/6 (33.3%)		0/3 (0%)
Nervous system disorders
Balance disorder	1/6 (16.7%)		0/3 (0%)
Dizziness	1/6 (16.7%)		2/3 (66.7%)
Dysgeusia	1/6 (16.7%)		0/3 (0%)
Peripheral neuropathy	6/6 (100%)		1/3 (33.3%)
Renal and urinary disorders
Pollakiuria	0/6 (0%)		1/3 (33.3%)
Respiratory, thoracic and mediastinal disorders
Cough	0/6 (0%)		1/3 (33.3%)
Skin and subcutaneous tissue disorders
Alopecia	2/6 (33.3%)		0/3 (0%)
Vascular disorders
Hypertension	1/6 (16.7%)		0/3 (0%)

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.