Efficacy and Safety Trial of ADU-S100 and Pembrolizumab in Head and Neck Cancer

• Sponsor: Chinook Therapeutics, Inc. (formerly Aduro) (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03937141
• Collaborator: (none)
• Enrollment: 16
• Locations: 17
• Arm: 1
• Actual Duration (Months): 21.5
• Patients Per Site: 0.9
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

ADU-CL-20 is an open-label, multicenter Phase 2 clinical trial to evaluate the efficacy and safety of intratumoral ADU-S100 (also referred to as MIW815) administered with pembrolizumab in the first-line setting. The population will consist of adults with PD-L1 positive recurrent or metastatic HNSCC.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Head and Neck Cancer; Recurrent Head and Neck Cancer	Drug: ADU-S100	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Efficacy and Safety Trial of ADU-S100 and Pembrolizumab in Adults With Head and Neck Cancer
• Actual Study Start Date: Aug 26, 2019
• Actual Primary Completion Date: May 10, 2021
• Actual Study Completion Date: Jun 10, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ADU-S100 and pembrolizumab All eligible subjects will receive intravenous (IV) infusions of pembrolizumab and intratumoral injections of ADU-S100.	Drug: ADU-S100; intratumoral; Other Names: MIW815

Outcome Measures

Primary Outcome Measures

1. Evaluation of Clinical Activity by the Objective Response Rate (ORR; Complete Response [CR] and Partial Response [PR]) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [Up to 25 months]

   To determine ORR of ADU-S100 in combination with pembrolizumab in subjects with recurrent or metastatic head and neck squamous cell cancer (HNSCC). ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 and as assessed by the investigator.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histological or cytological confirmation of recurrent or metastatic HNSCC

• Measurable disease as defined by RECIST v1.1

• PD-L1 positive

Exclusion Criteria:

• Diagnosis of recurrent or metastatic carcinoma of the nasopharynx, squamous cell carcinoma of unknown primary histology; or salivary gland or non-squamous histologies (e.g. mucosal melanoma)

• Disease amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy)

• Prior systemic anti-cancer therapy (use of chemotherapeutic agents, targeted small molecules, immunotherapy, or monoclonal antibodies) for the treatment of recurrent or metastatic HNSCC

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama Comprehensive Cancer Center	Birmingham	Alabama	United States	35294
2	University of Arizona Cancer Center	Tucson	Arizona	United States	85724
3	UC San Diego Moores Cancer Center	La Jolla	California	United States	92093
4	Yale University Cancer Center	New Haven	Connecticut	United States	06520
5	Moffitt Cancer Center	Tampa	Florida	United States	33612
6	Emory University Hospital	Atlanta	Georgia	United States	30308
7	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
8	University of Kansas	Westwood	Kansas	United States	66205
9	James Graham Brown Cancer Center	Louisville	Kentucky	United States	40202
10	University of Maryland, Greenebaum Comprehensive Cancer Center	Baltimore	Maryland	United States	21201
11	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
12	Regions Cancer Care Center	Saint Paul	Minnesota	United States	55101
13	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
14	University Pittsburgh Medical Center Hillman Cancer Center	Pittsburgh	Pennsylvania	United States	15232
15	MUSC Hollings Cancer Center	Charleston	South Carolina	United States	29425
16	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232
17	Baylor University Medical Center	Dallas	Texas	United States	75246

Sponsors and Collaborators

• Chinook Therapeutics, Inc. (formerly Aduro)

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jan 19, 2021
• Statistical Analysis Plan - Oct 9, 2020

More Information

Publications

None provided.

• Responsible Party: Chinook Therapeutics, Inc. (formerly Aduro)
• ClinicalTrials.gov Identifier: NCT03937141
• Other Study ID Numbers: ADU-CL-20
• First Posted: May 3, 2019
• Last Update Posted: Jan 3, 2022
• Last Verified: Dec 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Head and Neck Neoplasms

Study Results

Participant Flow

Recruitment Details	Participants were enrolled from 17 study centers in the United States.
Pre-assignment Detail	All enrolled subjects were included in the trial.

Arm/Group Title	ADU-S100 and Pembrolizumab
Arm/Group Description	All eligible subjects will receive intravenous (IV) infusions of pembrolizumab and intratumoral injections of ADU-S100. ADU-S100: intratumoral
Period Title: Overall Study
STARTED	16
COMPLETED	16
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	ADU-S100 and Pembrolizumab
Arm/Group Description	All eligible subjects will receive intravenous (IV) infusions of pembrolizumab and intratumoral injections of ADU-S100. ADU-S100: intratumoral
Overall Participants	16
Age, Customized (Count of Participants)
< 65	12 75%
>= 65	4 25%
Sex: Female, Male (Count of Participants)
Female	4 25%
Male	12 75%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	16 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 12.5%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 6.3%
White	13 81.3%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Evaluation of Clinical Activity by the Objective Response Rate (ORR; Complete Response [CR] and Partial Response [PR]) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Description	To determine ORR of ADU-S100 in combination with pembrolizumab in subjects with recurrent or metastatic head and neck squamous cell cancer (HNSCC). ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 and as assessed by the investigator.
Time Frame	Up to 25 months

Outcome Measure Data

Analysis Population Description

Analysis performed on subjects who had ≥ 1 post-baseline response assessment.

Arm/Group Title	ADU-S100 and Pembrolizumab
Arm/Group Description	All eligible subjects will receive intravenous (IV) infusions of pembrolizumab and intratumoral injections of ADU-S100. ADU-S100: intratumoral
Measure Participants	6
Complete Response	1 6.3%
Partial Response	5 31.3%

Adverse Events

Time Frame	Subjects were followed for serious and non-serious adverse events (AEs) from Screening until 30 days following the last dose of study drug, up to 1 year, 4 months.
Arm/Group Title	ADU-S100 and Pembrolizumab
Arm/Group Description	All eligible subjects will receive intravenous (IV) infusions of pembrolizumab and intratumoral injections of ADU-S100. ADU-S100: intratumoral
All Cause Mortality
	ADU-S100 and Pembrolizumab
	Affected / at Risk (%)	# Events
Total	6/16 (37.5%)
Serious Adverse Events
	ADU-S100 and Pembrolizumab
	Affected / at Risk (%)	# Events
Total	16/16 (100%)
Cardiac disorders
Stress cardiomyopathy	1/16 (6.3%)	1
Endocrine disorders
Hypophysitis	1/16 (6.3%)	1
Gastrointestinal disorders
Aphthous ulcer	1/16 (6.3%)	1
Colitis	1/16 (6.3%)	1
General disorders
Localised oedema	1/16 (6.3%)	1
Immune system disorders
Cytokine release syndrome	1/16 (6.3%)	1
Infections and infestations
Abscess jaw	1/16 (6.3%)	1
Sepsis	1/16 (6.3%)	1
Sinusitis	1/16 (6.3%)	1
Tooth abscess	1/16 (6.3%)	1
Metabolism and nutrition disorders
Hyponatraemia	1/16 (6.3%)	1
Lactic acidosis	1/16 (6.3%)	1
Musculoskeletal and connective tissue disorders
Neck pain	1/16 (6.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatocellular carcinoma	1/16 (6.3%)	1
Squamous cell carcinoma of the oral cavity	1/16 (6.3%)	1
Tumour pain	1/16 (6.3%)	1
Nervous system disorders
Carotid artery occlusion	1/16 (6.3%)	1
Cerebrovascular accident	1/16 (6.3%)	1
Presyncope	1/16 (6.3%)	1
Product Issues
Device malfunction	1/16 (6.3%)	1
Renal and urinary disorders
Acute kidney injury	1/16 (6.3%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/16 (6.3%)	1
Laryngeal oedema	1/16 (6.3%)	1
Pneumonia aspiration	1/16 (6.3%)	1
Vascular disorders
Hypertension	1/16 (6.3%)	1
Hypotension	1/16 (6.3%)	1
Other (Not Including Serious) Adverse Events
	ADU-S100 and Pembrolizumab
	Affected / at Risk (%)	# Events
Total	16/16 (100%)
Blood and lymphatic system disorders
Anaemia	7/16 (43.8%)	14
Iron deficiency anaemia	1/16 (6.3%)	2
Leukocytosis	1/16 (6.3%)	1
Thrombocytosis	1/16 (6.3%)	1
Cardiac disorders
Acute myocardial infarction	1/16 (6.3%)	1
Aortic valve disease	1/16 (6.3%)	1
Bradycardia	2/16 (12.5%)	2
Sinus tachycardia	1/16 (6.3%)	1
Stress cardiomyopathy	1/16 (6.3%)	1
Tachycardia	1/16 (6.3%)	1
Ventricular extrasystoles	1/16 (6.3%)	1
Ear and labyrinth disorders
Ear discomfort	1/16 (6.3%)	2
Ear pain	1/16 (6.3%)	2
Vertigo	1/16 (6.3%)	1
Endocrine disorders
Hyperthyroidism	1/16 (6.3%)	1
Hypophysitis	1/16 (6.3%)	1
Hypothyroidism	3/16 (18.8%)	3
Eye disorders
Eye inflammation	1/16 (6.3%)	1
Eye pruritus	1/16 (6.3%)	1
Vision blurred	1/16 (6.3%)	2
Gastrointestinal disorders
Abdominal distension	1/16 (6.3%)	1
Aphthous ulcer	1/16 (6.3%)	1
Colitis	1/16 (6.3%)	2
Constipation	6/16 (37.5%)	9
Diarrhoea	8/16 (50%)	10
Dysphagia	3/16 (18.8%)	4
Eructation	1/16 (6.3%)	1
Gastrointestinal haemorrhage	1/16 (6.3%)	1
Gastrooesophageal reflux disease	1/16 (6.3%)	1
Haemorrhoidal haemorrhage	1/16 (6.3%)	2
Ileus	2/16 (12.5%)	2
Mouth haemorrhage	1/16 (6.3%)	1
Nausea	8/16 (50%)	11
Oesophagitis	1/16 (6.3%)	1
Oral pain	1/16 (6.3%)	1
Salivary hypersecretion	1/16 (6.3%)	1
Vomiting	5/16 (31.3%)	7
General disorders
Chest pain	1/16 (6.3%)	2
Chills	5/16 (31.3%)	8
Face oedema	1/16 (6.3%)	1
Facial pain	1/16 (6.3%)	1
Fatigue	9/16 (56.3%)	12
Hypothermia	1/16 (6.3%)	1
Influenza like illness	1/16 (6.3%)	2
Injection site discharge	1/16 (6.3%)	1
Injection site pain	5/16 (31.3%)	21
Injection site scab	1/16 (6.3%)	1
Injection site scar	1/16 (6.3%)	1
Injection site swelling	2/16 (12.5%)	2
Injection site vesicles	1/16 (6.3%)	1
Localised oedema	3/16 (18.8%)	6
Oedema peripheral	2/16 (12.5%)	2
Pyrexia	6/16 (37.5%)	7
Secretion discharge	1/16 (6.3%)	1
Complications associated with device	1/16 (6.3%)	1
Immune system disorders
Cytokine release syndrome	1/16 (6.3%)	1
Sarcoidosis	1/16 (6.3%)	1
Infections and infestations
Abscess jaw	1/16 (6.3%)	1
Candida infection	1/16 (6.3%)	1
Clostridium difficile infection	1/16 (6.3%)	1
Device related infection	2/16 (12.5%)	2
Otitis media	1/16 (6.3%)	1
Pneumonia	2/16 (12.5%)	2
Sepsis	1/16 (6.3%)	1
Sinusitis	1/16 (6.3%)	1
Tooth abscess	1/16 (6.3%)	1
Upper respiratory tract infection	2/16 (12.5%)	3
Urinary tract infection	1/16 (6.3%)	2
Wound infection	3/16 (18.8%)	6
Injury, poisoning and procedural complications
Fall	1/16 (6.3%)	1
Post procedural haemorrhage	1/16 (6.3%)	1
Procedural pain	2/16 (12.5%)	2
Tibia fracture	1/16 (6.3%)	1
Investigations
Blood creatinine increased	1/16 (6.3%)	1
Blood iron decreased	1/16 (6.3%)	1
Blood lactate dehydrogenase increased	2/16 (12.5%)	4
Blood thyroid stimulating hormone increased	1/16 (6.3%)	1
Lymphocyte count decreased	1/16 (6.3%)	1
Platelet count increased	1/16 (6.3%)	3
Weight decreased	8/16 (50%)	13
White blood cell count increased	1/16 (6.3%)	1
Metabolism and nutrition disorders
Decrease appetite	3/16 (18.8%)	3
Dehydration	3/16 (18.8%)	4
Hypercalcaemia	2/16 (12.5%)	2
Hyperglycaemia	2/16 (12.5%)	2
Hyperphosphataemia	3/16 (18.8%)	3
Hypoalbuminaemia	1/16 (6.3%)	3
Hypocalcaemia	1/16 (6.3%)	1
Hypokalaemia	2/16 (12.5%)	4
Hypomagnesaemia	2/16 (12.5%)	3
Hyponatraemia	4/16 (25%)	8
Hypophosphataemia	3/16 (18.8%)	3
Hypovolaemia	1/16 (6.3%)	1
Lactic acidosis	1/16 (6.3%)	1
Malnutrition	2/16 (12.5%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	2/16 (12.5%)	2
Back pain	2/16 (12.5%)	2
Joint effusion	1/16 (6.3%)	1
Muscular weakness	4/16 (25%)	4
Musculoskeletal pain	1/16 (6.3%)	1
Musculoskeletal stiffness	1/16 (6.3%)	1
Myalgia	1/16 (6.3%)	1
Neck pain	3/16 (18.8%)	5
Pain in extremity	2/16 (12.5%)	2
Trismus	1/16 (6.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatocellular carcinoma	1/16 (6.3%)	1
Squamous cell carcinoma of the oral cavity	1/16 (6.3%)	1
Tumour pain	3/16 (18.8%)	7
Nervous system disorders
Amnesia	1/16 (6.3%)	1
Carotid artery occlusion	1/16 (6.3%)	1
Cerebrovascular accident	1/16 (6.3%)	1
Dizziness	3/16 (18.8%)	3
Dysarthria	1/16 (6.3%)	1
Dysgeusia	1/16 (6.3%)	1
Headache	5/16 (31.3%)	5
Presyncope	1/16 (6.3%)	1
Transient ischaemic attack	1/16 (6.3%)	1
Product Issues
Device malfunction	1/16 (6.3%)	1
Psychiatric disorders
Anxiety	1/16 (6.3%)	1
Insomnia	3/16 (18.8%)	3
Renal and urinary disorders
Acute kidney injury	1/16 (6.3%)	1
Pollakiuria	1/16 (6.3%)	1
Urinary retention	1/16 (6.3%)	1
Respiratory, thoracic and mediastinal disorders
Aphonia	1/16 (6.3%)	1
Bronchospasm	1/16 (6.3%)	1
Cough	1/16 (6.3%)	1
Dysphonia	1/16 (6.3%)	1
Dyspnoea	3/16 (18.8%)	3
Epistaxis	1/16 (6.3%)	1
Hiccups	1/16 (6.3%)	1
Laryngeal oedema	1/16 (6.3%)	1
Pleural effusion	2/16 (12.5%)	3
Pneumonia aspiration	2/16 (12.5%)	3
Productive cough	4/16 (25%)	4
Respiratory failure	2/16 (12.5%)	2
Skin and subcutaneous tissue disorders
Dermatitis bullous	1/16 (6.3%)	1
Dry skin	1/16 (6.3%)	1
Excessive granulation tissue	1/16 (6.3%)	1
Pruritus	3/16 (18.8%)	3
Rash	2/16 (12.5%)	3
Rash maculo-papular	1/16 (6.3%)	1
Skin ulcer	1/16 (6.3%)	2
Vascular disorders
Embolism	1/16 (6.3%)	1
Hot flush	1/16 (6.3%)	2
Hypertension	1/16 (6.3%)	2
Hypotension	5/16 (31.3%)	6
Lymphoedema	1/16 (6.3%)	1
Orthostatic hypotension	1/16 (6.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Disclosure restriction - study results first published in a joint multi-center paper unless (a) no multi-center publication, or (b) ≥18 months has passed since completion of the study. Thereafter, Investigator may publish provided that Investigator: (i) provides a copy of the publication to Chinook ≥ 45 days in advance of submission for publication; (ii) deletes Chinook Confidential Information (other than the Study results) and (iii) submission may be delayed up to 90 days to permit IP filings.