YATAGARASU: A Study of Apalutamide Combined With GnRH Agonist in Participants With Androgen Receptor Positive Salivary Gland Carcinoma

• Sponsor: Janssen Pharmaceutical K.K. (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT04325828
• Collaborator: (none)
• Enrollment: 31
• Locations: 7
• Arm: 1
• Anticipated Duration (Months): 37.5
• Patients Per Site: 4.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate the overall response rate (ORR) of apalutamide in combination with a gonadotropin-releasing hormone (GnRH) agonist in participants with androgen receptor (AR) expressing locally advanced or recurrent/metastatic salivary gland carcinoma (SGC).

Condition or Disease	Intervention/Treatment	Phase
Salivary Gland Neoplasms	Drug: Apalutamide; Drug: GnRH Agonist	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label Phase 2 Study to Evaluate the Efficacy and Safety of Apalutamide in Combination With Gonadotropin-releasing Hormone (GnRH) Agonist in Subjects With Locally Advanced or Recurrent/Metastatic and Androgen Receptor (AR) Expressing Salivary Gland Carcinoma
• Actual Study Start Date: Apr 7, 2020
• Actual Primary Completion Date: Jun 9, 2021
• Anticipated Study Completion Date: May 22, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Apalutamide plus GnRH Agonist Participants will receive apalutamide 240 milligram (mg) in combination with a gonadotropin-releasing hormone (GnRH) agonist until disease progression, unacceptable toxicity, death, or the end of the study and each treatment cycle will be of 28 days.	Drug: Apalutamide; Apalutamide 240 mg (4*60-mg tablets) will be administered orally once daily with or without food.; Other Names: JNJ-56021927 ; Drug: GnRH Agonist; A stable regimen of goserelin 3.6 mg will be administered as a GnRH agonist.

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (ORR) [Up to 13 months]

   Overall response rate (ORR) was defined as the percentage of participants who achieve partial response (PR) or better according to the response evaluation criteria in solid tumors (RECIST) version1.1, including with either confirmed best overall response of complete response (CR) or PR during the study. CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeters (mm). PR is defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, in absence of new lesions or unequivocal progression of non-target lesions.

Secondary Outcome Measures

1. Clinical Benefit Rate (CBR) [Up to 13 months]

   Clinical benefit rate (CBR) was defined as the percentage of participants who achieved a confirmed best overall response of CR, PR, or stable disease (SD) for at least 24 weeks based on RECIST version 1.1 during the study (and prior to subsequent therapy if any). CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, in absence of new lesions or unequivocal progression of non-target lesions. SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study.

2. Disease Control Rate (DCR) [Up to 13 months]

   DCR was defined as the percentage of participants who achieved a confirmed best overall response of CR, PR, or SD based on RECIST version 1.1 during the study (and prior to subsequent therapy if any). CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, in absence of new lesions or unequivocal progression of non-target lesions. SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study.

3. Progression-free Survival (PFS) as Assessed by ICRR [Up to 13 months]

   PFS was defined as the time from the date of the initial dose of study intervention to the date of first documented disease progression as defined in the RECIST version 1.1, or death due to any cause, whichever occurred first. Progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.

4. Overall Survival (OS) [Up to 13 months]

   Overall survival (OS) was defined as the time from the date of the initial dose of study intervention to the date of the participant's death.

5. Time to Response (TTR) [Up to 13 months]

   TTR was defined among responders (with a CR or PR) as the time between date of the initial dose of study intervention and the first efficacy evaluation that the participant had met all criteria for CR or PR. CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, in absence of new lesions or unequivocal progression of non-target lesions.

6. Duration of Response (DoR) [Up to 13 months]

   DoR calculated among responders from the date of initial documentation of a response (CR or PR) to the date of first documented evidence of progressive disease as defined in RECIST version 1.1 or death, whichever occurred first. CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is defined as at least a 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, in absence of new lesions or unequivocal progression of non-target lesions.

7. Number of Participants With Treatment-emergent Adverse Events (TEAEs) [Up to 13 months]

   Number of participants with TEAEs were reported. Treatment-emergent adverse events (TEAEs) for the treatment phase included events with an onset date/time on or after the start of study intervention through the day of last dose plus 30 days were considered as treatment-emergent.

8. Plasma Concentration of Apalutamide [Day 1 (predose) of Cycles 2 to 6 (each cycle was of 28 days)]

   Plasma concentration of apalutamide was reported.

9. Plasma Concentration of N-desmethyl Apalutamide [Day 1 (predose) of Cycles 2 to 6 (each cycle was of 28 days)]

   Plasma concentration of N-desmethyl Apalutamide was reported.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically confirmed salivary gland carcinoma (SGC) by local pathology

• Androgen receptor (AR) expressing SGC: Local testing of AR-positivity will be performed as standard of care for the eligibility confirmation. AR-positivity will be defined according to immunohistochemistry (IHC) staining of tumor tissue with at least 1 percent (%) of cell nuclei staining positive. Tissue should be available for the central confirmation of AR-positivity, but the central result of AR positivity will not be required for initiating the study intervention

• Locally advanced or recurrent/metastatic SGC

• Measurable lesion(s) according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

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

Exclusion Criteria:

• Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 30 days prior to first dose. Treatment with a drug that has a short half life (t1/2) (for example, less than [<] 1 day) may be eligible in accordance with the discussion with the sponsor's medical monitor

• Radiographically confirmed brain metastases. In case of history of brain metastases that were previously treated and not recurred for at least 6 months, they are considered eligible

• Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less (except for all grade alopecia, and for peripheral neuropathy, and hypothyroidism stable on hormone replacement therapy to be Grade 2 or less). If corticosteroids are administered for any reasons such as the management of toxicities due to prior therapies, the dose must be tapered until 10 milligram (mg)/day or less of prednisolone and contact the sponsor's medical monitor on an individual basis prior to the first dose

• Active or symptomatic viral hepatitis or chronic liver disease; ascites or bleeding disorders secondary to hepatic dysfunction

• History of seizure or any condition that may predispose to seizure (including, but not limited to, prior stroke, transient ischemic attack, or loss of consciousness less than or equal to [<=] 1 year prior to first dose; brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect)

• Treatment with drugs known to lower the seizure threshold within 4 weeks prior to first dose

• Known or suspected contraindications or hypersensitivity to apalutamide, gonadotropin-releasing hormone agonist (GnRHa) analogues or any of the components of the formulations

• Received prior ADT including a GnRH analogue, AR blocker such as bicalutamide, enzalutamide or 17alpha-hydroxylase-17,20-lyase (CYP17) inhibitor such as abiraterone acetate etc. Chemotherapy, radiation, or surgery as part of curative intent therapy are allowed so long as prior therapy did not include ADT. Prior chemotherapy, targeted cancer therapy or immunotherapy within 1 week or 4 half-lives whichever is longer, before the first administration of study drug. For agents with long half-lives, the maximum required time since last dose is 2 weeks

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Cancer Center Hospital	Chuo-Ku		Japan	104-0045
2	National Hospital Organization Kyushu Medical Center	Fukuoka		Japan	810-8563
3	Kansai Medical University Hospital	Hirakata		Japan	573-1191
4	National Hospital Organizaiton Shikoku Cancer Center	Matsuyama		Japan	791-0280
5	Aichi Cancer Center Hospital	Nagoya-Shi		Japan	464-8681
6	Niigata University Medical & Dental Hospital	Niigata		Japan	951-8520
7	Hokkaido University Hospital	Sapporo-shi		Japan	060-8648

Sponsors and Collaborators

• Janssen Pharmaceutical K.K.

Investigators

• Study Director: Janssen Pharmaceutical K.K., Japan Clinical Trial, Janssen Pharmaceutical K.K.

Study Documents (Full-Text)

• Study Protocol - Jul 21, 2021
• Statistical Analysis Plan - Feb 18, 2021

More Information

Publications

None provided.

• Responsible Party: Janssen Pharmaceutical K.K.
• ClinicalTrials.gov Identifier: NCT04325828
• Other Study ID Numbers: CR108758; 56021927SGT2001
• First Posted: Mar 30, 2020
• Last Update Posted: Aug 15, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Salivary Gland Neoplasms

Study Results

Participant Flow

Arm/Group Title	Apalutamide + Goserelin
Arm/Group Description	Participants with androgen receptor (AR) expressing locally advanced or recurrent/metastatic salivary gland carcinoma (SGC) received apalutamide 240 milligrams (mg) (4*60 mg tablets) orally once daily with or without food in combination with stable regimen of goserelin 3.6 mg administered subcutaneously once per cycle (each cycle is of 28 days) as a gonadotropin-releasing hormone (GnRH) agonist, until disease progression, unacceptable toxicity, death, or end of the study.
Period Title: Overall Study
STARTED	31
COMPLETED	5
NOT COMPLETED	26

Baseline Characteristics

Arm/Group Title	Apalutamide + Goserelin
Arm/Group Description	Participants with androgen receptor (AR) expressing locally advanced or recurrent/metastatic salivary gland carcinoma (SGC) received apalutamide 240 milligrams (mg) (4*60 mg tablets) orally once daily with or without food in combination with stable regimen of goserelin 3.6 mg administered subcutaneously once per cycle (each cycle is of 28 days) as a gonadotropin-releasing hormone (GnRH) agonist, until disease progression, unacceptable toxicity, death, or end of the study.
Overall Participants	31
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	65
Sex: Female, Male (Count of Participants)
Female	1 3.2%
Male	30 96.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	31 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	31 100%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (ORR)
Description	Overall response rate (ORR) was defined as the percentage of participants who achieve partial response (PR) or better according to the response evaluation criteria in solid tumors (RECIST) version1.1, including with either confirmed best overall response of complete response (CR) or PR during the study. CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeters (mm). PR is defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, in absence of new lesions or unequivocal progression of non-target lesions.
Time Frame	Up to 13 months

Outcome Measure Data

Analysis Population Description

Response evaluable set included all participants who were androgen receptor (AR) positive by local test and were confirmed evaluable by independent central radiology review (ICRR) and also, who received at least 1 dose of study drug and had at least 1 postbaseline disease assessment or died due to disease progression before first postbaseline disease assessment. Here, 'N' (number of participants analyzed) included 24 response evaluable participants who were analyzed for this outcome measure.

Arm/Group Title	Apalutamide + Goserelin
Arm/Group Description	Participants with androgen receptor (AR) expressing locally advanced or recurrent/metastatic salivary gland carcinoma (SGC) received apalutamide 240 milligrams (mg) (4*60 mg tablets) orally once daily with or without food in combination with stable regimen of goserelin 3.6 mg administered subcutaneously once per cycle (each cycle is of 28 days) as a gonadotropin-releasing hormone (GnRH) agonist, until disease progression, unacceptable toxicity, death, or end of the study.
Measure Participants	24
Number [percentage of participants]	25 80.6%

2. Secondary Outcome

Title	Clinical Benefit Rate (CBR)
Description	Clinical benefit rate (CBR) was defined as the percentage of participants who achieved a confirmed best overall response of CR, PR, or stable disease (SD) for at least 24 weeks based on RECIST version 1.1 during the study (and prior to subsequent therapy if any). CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, in absence of new lesions or unequivocal progression of non-target lesions. SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study.
Time Frame	Up to 13 months

Outcome Measure Data

Analysis Population Description

Response evaluable set included all participants who were AR positive by local test and who were confirmed evaluable by an ICRR and also, all participants who received at least 1 dose of study intervention and who had at least 1 postbaseline disease assessment or died due to disease progression before the first postbaseline disease assessment. Here, 'N' (number of participants analyzed) included 24 response evaluable participants who were analyzed for this outcome measure.

Arm/Group Title	Apalutamide + Goserelin
Arm/Group Description	Participants with androgen receptor (AR) expressing locally advanced or recurrent/metastatic salivary gland carcinoma (SGC) received apalutamide 240 milligrams (mg) (4*60 mg tablets) orally once daily with or without food in combination with stable regimen of goserelin 3.6 mg administered subcutaneously once per cycle (each cycle is of 28 days) as a gonadotropin-releasing hormone (GnRH) agonist, until disease progression, unacceptable toxicity, death, or end of the study.
Measure Participants	24
Number [percentage of participants]	50 161.3%

3. Secondary Outcome

Title	Disease Control Rate (DCR)
Description	DCR was defined as the percentage of participants who achieved a confirmed best overall response of CR, PR, or SD based on RECIST version 1.1 during the study (and prior to subsequent therapy if any). CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, in absence of new lesions or unequivocal progression of non-target lesions. SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study.
Time Frame	Up to 13 months

Outcome Measure Data

Analysis Population Description

Response evaluable set included all participants who were AR positive by local test and who were confirmed evaluable by an ICRR and also, all participants who received at least 1 dose of study intervention and who had at least 1 postbaseline disease assessment or died due to disease progression before the first postbaseline disease assessment. Here, 'N' (number of participants analyzed) included 24 response evaluable participants who were analyzed for this outcome measure.

Arm/Group Title	Apalutamide + Goserelin
Arm/Group Description	Participants with androgen receptor (AR) expressing locally advanced or recurrent/metastatic salivary gland carcinoma (SGC) received apalutamide 240 milligrams (mg) (4*60 mg tablets) orally once daily with or without food in combination with stable regimen of goserelin 3.6 mg administered subcutaneously once per cycle (each cycle is of 28 days) as a gonadotropin-releasing hormone (GnRH) agonist, until disease progression, unacceptable toxicity, death, or end of the study.
Measure Participants	24
Number [percentage of participants]	70.8 228.4%

4. Secondary Outcome

Title	Progression-free Survival (PFS) as Assessed by ICRR
Description	PFS was defined as the time from the date of the initial dose of study intervention to the date of first documented disease progression as defined in the RECIST version 1.1, or death due to any cause, whichever occurred first. Progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
Time Frame	Up to 13 months

Outcome Measure Data

Analysis Population Description

Treated analysis set included all participants who received at least 1 dose of study intervention.

Arm/Group Title	Apalutamide + Goserelin
Arm/Group Description	Participants with androgen receptor (AR) expressing locally advanced or recurrent/metastatic salivary gland carcinoma (SGC) received apalutamide 240 milligrams (mg) (4*60 mg tablets) orally once daily with or without food in combination with stable regimen of goserelin 3.6 mg administered subcutaneously once per cycle (each cycle is of 28 days) as a gonadotropin-releasing hormone (GnRH) agonist, until disease progression, unacceptable toxicity, death, or end of the study.
Measure Participants	31
Median (95% Confidence Interval) [months]	7.43

5. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival (OS) was defined as the time from the date of the initial dose of study intervention to the date of the participant's death.
Time Frame	Up to 13 months

Outcome Measure Data

Analysis Population Description

Treated analysis set included all participants who received at least 1 dose of study intervention.

Arm/Group Title	Apalutamide + Goserelin
Arm/Group Description	Participants with androgen receptor (AR) expressing locally advanced or recurrent/metastatic salivary gland carcinoma (SGC) received apalutamide 240 milligrams (mg) (4*60 mg tablets) orally once daily with or without food in combination with stable regimen of goserelin 3.6 mg administered subcutaneously once per cycle (each cycle is of 28 days) as a gonadotropin-releasing hormone (GnRH) agonist, until disease progression, unacceptable toxicity, death, or end of the study.
Measure Participants	31
Median (95% Confidence Interval) [months]	NA

6. Secondary Outcome

Title	Time to Response (TTR)
Description	TTR was defined among responders (with a CR or PR) as the time between date of the initial dose of study intervention and the first efficacy evaluation that the participant had met all criteria for CR or PR. CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, in absence of new lesions or unequivocal progression of non-target lesions.
Time Frame	Up to 13 months

Outcome Measure Data

Analysis Population Description

Population analyzed included response evaluable set amongst who were responders (CR or PR).

Arm/Group Title	Apalutamide + Goserelin
Arm/Group Description	Participants with androgen receptor (AR) expressing locally advanced or recurrent/metastatic salivary gland carcinoma (SGC) received apalutamide 240 milligrams (mg) (4*60 mg tablets) orally once daily with or without food in combination with stable regimen of goserelin 3.6 mg administered subcutaneously once per cycle (each cycle is of 28 days) as a gonadotropin-releasing hormone (GnRH) agonist, until disease progression, unacceptable toxicity, death, or end of the study.
Measure Participants	6
Median (Full Range) [months]	1.87

7. Secondary Outcome

Title	Duration of Response (DoR)
Description	DoR calculated among responders from the date of initial documentation of a response (CR or PR) to the date of first documented evidence of progressive disease as defined in RECIST version 1.1 or death, whichever occurred first. CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is defined as at least a 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, in absence of new lesions or unequivocal progression of non-target lesions.
Time Frame	Up to 13 months

Outcome Measure Data

Analysis Population Description

Population analyzed included response evaluable set amongst who were responders (CR or PR).

Arm/Group Title	Apalutamide + Goserelin
Arm/Group Description	Participants with androgen receptor (AR) expressing locally advanced or recurrent/metastatic salivary gland carcinoma (SGC) received apalutamide 240 milligrams (mg) (4*60 mg tablets) orally once daily with or without food in combination with stable regimen of goserelin 3.6 mg administered subcutaneously once per cycle (each cycle is of 28 days) as a gonadotropin-releasing hormone (GnRH) agonist, until disease progression, unacceptable toxicity, death, or end of the study.
Measure Participants	6
Median (95% Confidence Interval) [months]	NA

8. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Description	Number of participants with TEAEs were reported. Treatment-emergent adverse events (TEAEs) for the treatment phase included events with an onset date/time on or after the start of study intervention through the day of last dose plus 30 days were considered as treatment-emergent.
Time Frame	Up to 13 months

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study intervention.

Arm/Group Title	Apalutamide + Goserelin
Arm/Group Description	Participants with androgen receptor (AR) expressing locally advanced or recurrent/metastatic salivary gland carcinoma (SGC) received apalutamide 240 milligrams (mg) (4*60 mg tablets) orally once daily with or without food in combination with stable regimen of goserelin 3.6 mg administered subcutaneously once per cycle (each cycle is of 28 days) as a gonadotropin-releasing hormone (GnRH) agonist, until disease progression, unacceptable toxicity, death, or end of the study.
Measure Participants	31
Count of Participants [Participants]	28 90.3%

9. Secondary Outcome

Title	Plasma Concentration of Apalutamide
Description	Plasma concentration of apalutamide was reported.
Time Frame	Day 1 (predose) of Cycles 2 to 6 (each cycle was of 28 days)

Outcome Measure Data

Analysis Population Description

Pharmacokinetics analysis set included all participants with at least 1 apalutamide and/or N-desmethyl apalutamide concentration data after the first study intervention administration. Here, 'N' (number of participants analyzed) specifies all participants who were evaluated for this outcome measure (OM). Here, 'n' (number analyzed) specifies the number of participants evaluated at specified timepoints.

Arm/Group Title	Apalutamide + Goserelin
Arm/Group Description	Participants with androgen receptor (AR) expressing locally advanced or recurrent/metastatic salivary gland carcinoma (SGC) received apalutamide 240 milligrams (mg) (4*60 mg tablets) orally once daily with or without food in combination with stable regimen of goserelin 3.6 mg administered subcutaneously once per cycle (each cycle is of 28 days) as a gonadotropin-releasing hormone (GnRH) agonist, until disease progression, unacceptable toxicity, death, or end of the study.
Measure Participants	29
Cycle 02 Day 1, Predose	4.67 (1.19)
Cycle 03 Day 1, Predose	4.32 (1.35)
Cycle 04 Day 1, Predose	4.05 (1.46)
Cycle 05 Day 1, Predose	4.18 (1.38)
Cycle 06 Day 1, Predose	4.16 (1.52)

10. Secondary Outcome

Title	Plasma Concentration of N-desmethyl Apalutamide
Description	Plasma concentration of N-desmethyl Apalutamide was reported.
Time Frame	Day 1 (predose) of Cycles 2 to 6 (each cycle was of 28 days)

Outcome Measure Data

Analysis Population Description

Pharmacokinetics analysis set included all participants with at least 1 apalutamide and/or N-desmethyl apalutamide concentration data after the first study intervention administration. Here, 'N' (number of participants analyzed) specifies all participants who were evaluated for this OM. Here, 'n' (number analyzed) specifies the number of participants evaluated at specified timepoints.

Arm/Group Title	Apalutamide + Goserelin
Arm/Group Description	Participants with androgen receptor (AR) expressing locally advanced or recurrent/metastatic salivary gland carcinoma (SGC) received apalutamide 240 milligrams (mg) (4*60 mg tablets) orally once daily with or without food in combination with stable regimen of goserelin 3.6 mg administered subcutaneously once per cycle (each cycle is of 28 days) as a gonadotropin-releasing hormone (GnRH) agonist, until disease progression, unacceptable toxicity, death, or end of the study.
Measure Participants	29
Cycle 02 Day 1, Predose	7.19 (1.21)
Cycle 03 Day 1, Predose	6.89 (1.56)
Cycle 04 Day 1, Predose	6.29 (1.66)
Cycle 05 Day 1, Predose	6.53 (1.81)
Cycle 06 Day 1, Predose	6.40 (1.91)

Adverse Events

Time Frame	Up to 13 months
Adverse Event Reporting Description	Safety analysis set included all participants who received at least 1 dose of study intervention.
Arm/Group Title	Apalutamide + Goserelin
Arm/Group Description	Participants with androgen receptor (AR) expressing locally advanced or recurrent/metastatic salivary gland carcinoma (SGC) received apalutamide 240 milligrams (mg) (4*60 mg tablets) orally once daily with or without food in combination with stable regimen of goserelin 3.6 mg administered subcutaneously once per cycle (each cycle is of 28 days) as a gonadotropin-releasing hormone (GnRH) agonist, until disease progression, unacceptable toxicity, death, or end of the study.
All Cause Mortality
	Apalutamide + Goserelin
	Affected / at Risk (%)	# Events
Total	4/31 (12.9%)
Serious Adverse Events
	Apalutamide + Goserelin
	Affected / at Risk (%)	# Events
Total	5/31 (16.1%)
Blood and lymphatic system disorders
Anaemia	1/31 (3.2%)
Gastrointestinal disorders
Oesophageal Stenosis	1/31 (3.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer Pain	2/31 (6.5%)
Nervous system disorders
Cerebral Infarction	1/31 (3.2%)
Renal and urinary disorders
Hydronephrosis	1/31 (3.2%)
Respiratory, thoracic and mediastinal disorders
Laryngeal Oedema	1/31 (3.2%)
Other (Not Including Serious) Adverse Events
	Apalutamide + Goserelin
	Affected / at Risk (%)	# Events
Total	28/31 (90.3%)
Blood and lymphatic system disorders
Anaemia	4/31 (12.9%)
Leukopenia	3/31 (9.7%)
Lymphopenia	2/31 (6.5%)
Endocrine disorders
Hypothyroidism	6/31 (19.4%)
Gastrointestinal disorders
Constipation	3/31 (9.7%)
Diarrhoea	2/31 (6.5%)
Nausea	4/31 (12.9%)
Stomatitis	2/31 (6.5%)
General disorders
Malaise	5/31 (16.1%)
Infections and infestations
Upper Respiratory Tract Infection	2/31 (6.5%)
Injury, poisoning and procedural complications
Radiation Skin Injury	2/31 (6.5%)
Investigations
Blood Creatinine Increased	2/31 (6.5%)
Blood Thyroid Stimulating Hormone Increased	3/31 (9.7%)
Weight Decreased	4/31 (12.9%)
Metabolism and nutrition disorders
Decreased Appetite	2/31 (6.5%)
Hypertriglyceridaemia	3/31 (9.7%)
Musculoskeletal and connective tissue disorders
Myalgia	5/31 (16.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer Pain	2/31 (6.5%)
Nervous system disorders
Dizziness	2/31 (6.5%)
Headache	3/31 (9.7%)
Psychiatric disorders
Insomnia	5/31 (16.1%)
Respiratory, thoracic and mediastinal disorders
Cough	2/31 (6.5%)
Dysphonia	2/31 (6.5%)
Skin and subcutaneous tissue disorders
Dry Skin	3/31 (9.7%)
Rash	8/31 (25.8%)
Rash Maculo-Papular	10/31 (32.3%)
Vascular disorders
Hot Flush	6/31 (19.4%)
Hypotension	2/31 (6.5%)

Limitations/Caveats

Due to the low numbers of female participants, it was difficult to interpret the difference between males and females. There was a lack of data on individual treatment of apalutamide as well as goserelin. The number of participants in this study was limited, and the follow-up period was immature at this cut-off for the primary analysis.

More Information

Certain Agreements

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

If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.