Axitinib and Pembrolizumab in Subjects With Advanced Alveolar Soft Part Sarcoma and Other Soft Tissue Sarcomas

• ClinicalTrials.gov Identifier: NCT02636725
• Recruitment Status: Completed
• First Posted: December 22, 2015
• Results First Posted: November 26, 2021
• Last Update Posted: April 26, 2023
• Sponsor: Jonathan Trent, MD, PhD
• Collaborators: Merck Sharp & Dohme LLC; Pfizer
• Information provided by (Responsible Party): Jonathan Trent, MD, PhD, University of Miami

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Alveolar Soft Part Sarcoma; Soft Tissue Sarcomas
• Interventions: Drug: Axitinib; Drug: Pembrolizumab
• Enrollment: 33

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Axitinib Plus Pembrolizumab Group
Arm/Group Description	Participants in this group will receive combination treatment of Axitinib plus Pembrolizumab for up to 2 years followed by monotherapy of Axitinib until withdrawal of consent, disease progression and/or unacceptable toxicity as assessed by treating physician, whichever occurs first. Axitinib: 5 mg tablets twice daily oral dose administered for 7 consecutive weeks on Cycle 1. A safety lead-in consisting of the initial five patients, intrapatient dose escalation of Axitinib will be permitted based on the absence of predefined toxicities. Twice daily oral dose between 2 mg to 10 mg Axitinib tablets will be administered on subsequent 6 week cycles until withdrawal of consent, disease progression and/or unacceptable toxicity as assessed by treating physician, whichever occurs first. Pembrolizumab: 200 mg intravenous infusion administered every 21 weeks beginning week 2 of Cycle 1 for a maximum of up to 2 years or until withdrawal of consent, disease progression and/or unacceptable toxicity as assessed by treating physician, whichever occurs first.
Period Title: Baseline
Started	33
Completed	30
Not Completed	3
Reason Not Completed
Adverse Event	1
Lack of Efficacy	2
Period Title: Post-Baseline Imaging Assessment
Started	30
Completed	30
Not Completed	0

Baseline Characteristics

Arm/Group Title		Axitinib Plus Pembrolizumab Group
Arm/Group Description		Participants in this group will receive combination treatment of Axitinib plus Pembrolizumab for up to 2 years followed by monotherapy of Axitinib until withdrawal of consent, disease progression and/or unacceptable toxicity as assessed by treating physician, whichever occurs first. Axitinib: 5 mg tablets twice daily oral dose administered for 7 consecutive weeks on Cycle 1. A safety lead-in consisting of the initial five patients, intrapatient dose escalation of Axitinib will be permitted based on the absence of predefined toxicities. Twice daily oral dose between 2 mg to 10 mg Axitinib tablets will be administered on subsequent 6 week cycles until withdrawal of consent, disease progression and/or unacceptable toxicity as assessed by treating physician, whichever occurs first. Pembrolizumab: 200 mg intravenous infusion administered every 21 weeks beginning week 2 of Cycle 1 for a maximum of up to 2 years or until withdrawal of consent, disease progression and/or unacceptable toxicity as assessed by treating physician, whichever occurs first.
Overall Number of Baseline Participants		33
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	33 participants
	<=18 years	1 3.0%
	Between 18 and 65 years	24 72.7%
	>=65 years	8 24.2%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	33 participants
	Female	15 45.5%
	Male	18 54.5%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	33 participants
	Hispanic or Latino	8 24.2%
	Not Hispanic or Latino	25 75.8%
	Unknown or Not Reported	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	33 participants
	American Indian or Alaska Native	0 0.0%
	Asian	2 6.1%
	Native Hawaiian or Other Pacific Islander	1 3.0%
	Black or African American	0 0.0%
	White	29 87.9%
	More than one race	1 3.0%
	Unknown or Not Reported	0 0.0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Evaluable Participants Achieving Progression-Free Survival (PFS) at 3 Months
Description	Percentage of participants who are disease progression free 3 months after initiation of therapy. Disease progression will be evaluated from imaging measures using the Response Evaluation Criteria for Solid Tumors (RECIST) 1.1.
Time Frame	3 Months

Outcome Measure Data

Analysis Population Description

Evaluable participants received 80% of scheduled axitinib doses and two infusions of pembrolizumab, have measurable disease at baseline and at least one post-baseline disease assessment.

Arm/Group Title	Axitinib Plus Pembrolizumab Group
Arm/Group Description:	Participants in this group will receive combination treatment of Axitinib plus Pembrolizumab for up to 2 years followed by monotherapy of Axitinib until withdrawal of consent, disease progression and/or unacceptable toxicity as assessed by treating physician, whichever occurs first. Axitinib: 5 mg tablets twice daily oral dose administered for 7 consecutive weeks on Cycle 1. A safety lead-in consisting of the initial five patients, intrapatient dose escalation of Axitinib will be permitted based on the absence of predefined toxicities. Twice daily oral dose between 2 mg to 10 mg Axitinib tablets will be administered on subsequent 6 week cycles until withdrawal of consent, disease progression and/or unacceptable toxicity as assessed by treating physician, whichever occurs first. Pembrolizumab: 200 mg intravenous infusion administered every 21 weeks beginning week 2 of Cycle 1 for a maximum of up to 2 years or until withdrawal of consent, disease progression and/or unacceptable toxicity as assessed by treating physician, whichever occurs first.
Overall Number of Participants Analyzed	30
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	70; (50.3 to 83.1)

2. Secondary Outcome

Title	Percentage of Evaluable Participants Achieving Objective Response Rate (ORR)
Description	Objective Response Rate (ORR) is defined as achieving complete response (CR) or partial response (PR) from imaging measures using (RECIST) 1.1.
Time Frame	Up to 2 Years

Outcome Measure Data Not Reported

3. Secondary Outcome

Title	Percentage of Evaluable Participants Achieving Clinical Benefit Response (CBR)
Description	CBR is defined as achieving complete response (CR), partial response (PR) or stable disease (SD) from imaging measures using (RECIST) 1.1.
Time Frame	Up to 2 Years

Outcome Measure Data Not Reported

4. Secondary Outcome

Title	Time to Progression (TTP)
Description	Time to progression (TTP) is defined as time from treatment initiation to first occurrence of progression by Response Evaluation Criteria for Solid Tumors (RECIST) 1.1 or death.
Time Frame	Up to 2 years

Outcome Measure Data Not Reported

5. Secondary Outcome

Title	Overall Survival (OS)
Description	OS is (OS) is defined as the elapsed time from treatment initiation to death from any cause, whichever is earlier. Patients alive or those lost to follow-up will be censored at the last date of contact (or last date known to be alive).
Time Frame	Up to 5 years

Outcome Measure Data Not Reported

6. Secondary Outcome

Title	Number of Participants Experiencing Serious Adverse Events (SAEs), Dose-Limiting Toxicities, and Grade 3 or Higher Treatment-Emergent Adverse Events
Description	The number of participants experiencing serious adverse events (SAEs), dose-limiting toxicities (DLTs), and grade 3 or higher treatment-emergent adverse events (AEs). AEs, SAEs and DLTs will be evaluated by treating physician using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03. Treatment-emergent adverse events are those found to be definitely, probably and possibly related to study therapy.
Time Frame	Up to 25 months

Outcome Measure Data Not Reported

Adverse Events

Time Frame	Up to 3 years
Adverse Event Reporting Description	In this protocol, adverse events include only treatment-emergent adverse events. Adverse events that are definitely, probably or possible related to study therapy are reported.
Arm/Group Title	Axitinib Plus Pembrolizumab Group
Arm/Group Description	Participants in this group will receive combination treatment of Axitinib plus Pembrolizumab for up to 2 years followed by monotherapy of Axitinib until withdrawal of consent, disease progression and/or unacceptable toxicity as assessed by treating physician, whichever occurs first. Axitinib: 5 mg tablets twice daily oral dose administered for 7 consecutive weeks on Cycle 1. A safety lead-in consisting of the initial five patients, intrapatient dose escalation of Axitinib will be permitted based on the absence of predefined toxicities. Twice daily oral dose between 2 mg to 10 mg Axitinib tablets will be administered on subsequent 6 week cycles until withdrawal of consent, disease progression and/or unacceptable toxicity as assessed by treating physician, whichever occurs first. Pembrolizumab: 200 mg intravenous infusion administered every 21 weeks beginning week 2 of Cycle 1 for a maximum of up to 2 years or until withdrawal of consent, disease progression and/or unacceptable toxicity as assessed by treating physician, whichever occurs first.
All-Cause Mortality
	Axitinib Plus Pembrolizumab Group
	Affected / at Risk (%)
Total	17/33 (51.52%)
Serious Adverse Events
	Axitinib Plus Pembrolizumab Group
	Affected / at Risk (%)	# Events
Total	9/33 (27.27%)
Cardiac disorders
Pericardial effusion † 1	1/33 (3.03%)	1
Gastrointestinal disorders
Abdominal Pain † 1	1/33 (3.03%)	1
Diarrhea † 1	1/33 (3.03%)	2
Nausea and Vomiting † 1	1/33 (3.03%)	1
Vomiting † 1	1/33 (3.03%)	1
Infections and infestations
Papulopustular rash † 1	1/33 (3.03%)	1
Investigations
Alanine aminotransferase increased † 1	1/33 (3.03%)	1
Aspartate aminotransferase increased † 1	1/33 (3.03%)	1
Transaminitis † 1	1/33 (3.03%)	1
Metabolism and nutrition disorders
Anorexia † 1	1/33 (3.03%)	1
Dehydration † 1	1/33 (3.03%)	1
Hypertriglyceridemia † 1	1/33 (3.03%)	1
Musculoskeletal and connective tissue disorders
Back pain † 1	1/33 (3.03%)	1
Nervous system disorders
Radiculitis † 1	1/33 (3.03%)	1
Seizure † 1	2/33 (6.06%)	2
Syncope † 1	1/33 (3.03%)	1
Renal and urinary disorders
Acute renal failure † 1	1/33 (3.03%)	1
Uremia † 1	1/33 (3.03%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea † 1	2/33 (6.06%)	2
Pneumothorax † 1	1/33 (3.03%)	2
1 Term from vocabulary, CTCAE (4.03); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Axitinib Plus Pembrolizumab Group
	Affected / at Risk (%)	# Events
Total	33/33 (100.00%)
Blood and lymphatic system disorders
Anemia † 1	3/33 (9.09%)	4
Cardiac disorders
Chest Pain - Cardiac † 1	1/33 (3.03%)	1
Ear and labyrinth disorders
Ear congestion † 1	4/33 (12.12%)	4
Ear Pain † 1	1/33 (3.03%)	1
Vertigo † 1	1/33 (3.03%)	1
Endocrine disorders
Hyperthyroidism † 1	2/33 (6.06%)	4
Hypothyroidism † 1	18/33 (54.55%)	18
Gastrointestinal disorders
Abdominal Pain † 1	10/33 (30.30%)	15
Bloating † 1	2/33 (6.06%)	5
Constipation † 1	8/33 (24.24%)	8
Diarrhea † 1	18/33 (54.55%)	39
Dry Mouth † 1	3/33 (9.09%)	3
Dyspepsia † 1	1/33 (3.03%)	1
Gastroesophageal reflux disease † 1	5/33 (15.15%)	5
Acid reflux † 1	1/33 (3.03%)	1
Mouth sensitivity † 1	3/33 (9.09%)	3
Mouth soreness † 1	1/33 (3.03%)	1
Rectal irritation † 1	1/33 (3.03%)	1
Stomatitis † 1	1/33 (3.03%)	1
Hemorrhoids † 1	3/33 (9.09%)	4
Mucositis Oral † 1	13/33 (39.39%)	25
Nausea † 1	17/33 (51.52%)	27
Oral dysesthesia † 1	2/33 (6.06%)	2
Oral hemorrhage † 1	2/33 (6.06%)	2
Oral Pain † 1	2/33 (6.06%)	2
Stomach pain † 1	1/33 (3.03%)	1
Toothache † 1	1/33 (3.03%)	1
Vomiting † 1	11/33 (33.33%)	14
General disorders
Chills † 1	1/33 (3.03%)	1
Edema face † 1	1/33 (3.03%)	1
Edema limbs † 1	1/33 (3.03%)	1
Fatigue † 1	26/33 (78.79%)	53
Decreased appetite † 1	1/33 (3.03%)	1
Headaches (morning) † 1	1/33 (3.03%)	1
Itching skin † 1	1/33 (3.03%)	2
Weakness † 1	1/33 (3.03%)	1
Non-cardiac chest pain † 1	4/33 (12.12%)	5
Pain † 1	9/33 (27.27%)	12
Immune system disorders
Disseminated Herpes Zoster † 1	1/33 (3.03%)	1
Infections and infestations
Herpes simplex - Eye lesion † 1	1/33 (3.03%)	1
Papulopustular rash † 1	4/33 (12.12%)	5
Rash pustular † 1	1/33 (3.03%)	1
Injury, poisoning and procedural complications
Bruising † 1	1/33 (3.03%)	1
Investigations
Alanine aminotransferase increased † 1	11/33 (33.33%)	23
Alkaline phosphatase increased † 1	7/33 (21.21%)	12
Aspartate aminotransferase increased † 1	11/33 (33.33%)	18
Blood bilirubin increased † 1	1/33 (3.03%)	1
Creatinine increased † 1	5/33 (15.15%)	7
Ejection fraction decreased † 1	1/33 (3.03%)	1
Hemoglobin increased † 1	5/33 (15.15%)	7
Elevated triglycerides † 1	1/33 (3.03%)	1
Elevated thyroid stimulating hormone (TSH) † 1	3/33 (9.09%)	3
Eosinophilia † 1	1/33 (3.03%)	1
Hand sensitivity † 1	2/33 (6.06%)	2
Hyperlipidemia † 1	1/33 (3.03%)	1
Increased blood urea nitrogen (BUN) † 1	1/33 (3.03%)	2
Lung discomfort † 1	1/33 (3.03%)	1
Mouth sensitivity † 1	1/33 (3.03%)	1
Mouth sensitivity - spicy foods † 1	1/33 (3.03%)	1
Mouth sores † 1	1/33 (3.03%)	2
Muscle aches † 1	1/33 (3.03%)	1
Sputum production † 1	1/33 (3.03%)	1
Platelet count decreased † 1	3/33 (9.09%)	3
Weight loss † 1	4/33 (12.12%)	4
White blood cell decreased † 1	2/33 (6.06%)	2
Metabolism and nutrition disorders
Acidosis † 1	1/33 (3.03%)	1
Anorexia † 1	10/33 (30.30%)	24
Hyperglycemia † 1	3/33 (9.09%)	3
Hypertriglyceridemia † 1	1/33 (3.03%)	3
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/33 (3.03%)	1
Back Pain † 1	3/33 (9.09%)	3
Chest wall pain † 1	2/33 (6.06%)	2
Joint effusion † 1	2/33 (6.06%)	3
Foot sensitivity † 1	1/33 (3.03%)	1
Hand sensitivity † 1	2/33 (6.06%)	2
Intermittent hand sensitivity † 1	1/33 (3.03%)	1
Oligoarthritis † 1	1/33 (3.03%)	1
Pain in extremity † 1	5/33 (15.15%)	5
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain † 1	7/33 (21.21%)	7
Nervous system disorders
Headache † 1	4/33 (12.12%)	8
Hand sensitivity † 1	1/33 (3.03%)	1
Right-sided sciatica † 1	1/33 (3.03%)	1
Paresthesia † 1	1/33 (3.03%)	1
Syncope † 1	1/33 (3.03%)	1
Psychiatric disorders
Insomnia † 1	5/33 (15.15%)	5
Renal and urinary disorders
Hematuria † 1	1/33 (3.03%)	1
Proteinuria † 1	2/33 (6.06%)	2
Urinary urgency † 1	1/33 (3.03%)	1
Glycosuria † 1	1/33 (3.03%)	1
Reproductive system and breast disorders
Breast Pain † 1	1/33 (3.03%)	1
Vaginal irritation † 1	2/33 (6.06%)	3
Respiratory, thoracic and mediastinal disorders
Allergic Rhinitis † 1	2/33 (6.06%)	2
Cough † 1	11/33 (33.33%)	14
Dyspnea † 1	2/33 (6.06%)	3
Epistaxis † 1	1/33 (3.03%)	1
Hoarseness † 1	6/33 (18.18%)	7
Nasal congestion † 1	6/33 (18.18%)	6
Postnasal drip † 1	2/33 (6.06%)	2
Hemoptysis † 1	1/33 (3.03%)	1
Rhinorrhea † 1	1/33 (3.03%)	1
Shortness of breath with exertion † 1	1/33 (3.03%)	1
Wheezing † 1	2/33 (6.06%)	2
Skin and subcutaneous tissue disorders
Alopecia † 1	1/33 (3.03%)	1
Dry skin † 1	1/33 (3.03%)	1
Erythema multiforme † 1	1/33 (3.03%)	1
Palmar-plantar erythrodysesthesia syndrome † 1	8/33 (24.24%)	10
Rash acneiform † 1	1/33 (3.03%)	1
Rash maculo-papular † 1	1/33 (3.03%)	1
Acne † 1	1/33 (3.03%)	1
Eczema exacerbation † 1	1/33 (3.03%)	1
Fingertip sensitivity † 1	1/33 (3.03%)	1
Foot rash † 1	1/33 (3.03%)	1
Foot sensitivity † 1	2/33 (6.06%)	2
Hand and foot sensitivity † 1	1/33 (3.03%)	1
Lip skin thickening † 1	1/33 (3.03%)	1
Skin irritation † 1	1/33 (3.03%)	1
Telangiectasia † 1	1/33 (3.03%)	1
Vascular disorders
Hypertension † 1	13/33 (39.39%)	20
Hypotension † 1	1/33 (3.03%)	1
Thromboembolic event † 1	1/33 (3.03%)	1
1 Term from vocabulary, CTCAE (4.03); † Indicates events were collected by systematic assessment

Limitations and Caveats

Arm 2, the Axitinib Plus Pembrolizumab Expansion Cohort, did not open.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Jonathan Trent MD
• Organization: University of Miami
• Phone: 305-243-2581
• EMail: JTrent@med.miami.edu

Publications of Results:

Wilky BA, Trucco MM, Subhawong TK, Florou V, Park W, Kwon D, Wieder ED, Kolonias D, Rosenberg AE, Kerr DA, Sfakianaki E, Foley M, Merchan JR, Komanduri KV, Trent JC. Axitinib plus pembrolizumab in patients with advanced sarcomas including alveolar soft-part sarcoma: a single-centre, single-arm, phase 2 trial. Lancet Oncol. 2019 Jun;20(6):837-848. doi: 10.1016/S1470-2045(19)30153-6. Epub 2019 May 8.

• Responsible Party: Jonathan Trent, MD, PhD, University of Miami
• ClinicalTrials.gov Identifier: NCT02636725
• Other Study ID Numbers: 20150932
• First Submitted: December 14, 2015
• First Posted: December 22, 2015
• Results First Submitted: October 1, 2021
• Results First Posted: November 26, 2021
• Last Update Posted: April 26, 2023