Trial Outcomes & Findings for An Extension Protocol for Subjects Who Were Previously Enrolled in Other Tivantinib (ARQ 197) Protocols (NCT NCT01178411)

Last Updated: 2021-03-10

Results Overview

The duration of ARQ 197 exposure in this study was calculated as \[(date of last dose of study drug - date of first dose of study drug) + 1\]. Results refer to duration of ARQ 197 treatment in the present study only (i.e., does not include treatment received during participation in "feeder" studies).

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

60 participants

Primary outcome timeframe

Up to 3,021 days (up to 14-Jan-2019)

Results posted on

2021-03-10

Participant Flow

Adult male and female participants previously enrolled in phase 1 or phase 2 studies of tivantinib (ARQ 197) were eligible for enrollment.

Participant milestones

Participant milestones
Measure	Tivantinib (Monotherapy or Combination) Participants received tivantinib 360 mg twice daily by mouth as monotherapy or combination therapy.
Overall Study STARTED	60
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	60

Reasons for withdrawal

Reasons for withdrawal
Measure	Tivantinib (Monotherapy or Combination) Participants received tivantinib 360 mg twice daily by mouth as monotherapy or combination therapy.
Overall Study Adverse Event	5
Overall Study Withdrawal by Subject	4
Overall Study Protocol Violation	1
Overall Study Progressive disease per RECIST	32
Overall Study Progressive disease per clinician	9
Overall Study Physician Decision	6
Overall Study Death	1
Overall Study No reason provided	1
Overall Study Drug manufacturing ended	1

Baseline Characteristics

An Extension Protocol for Subjects Who Were Previously Enrolled in Other Tivantinib (ARQ 197) Protocols

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tivantinib (Monotherapy or Combination) n=60 Participants Participants received tivantinib 360 mg twice daily by mouth as monotherapy or combination therapy.
Age, Continuous	61.6 Years STANDARD_DEVIATION 14.79 • n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants
Sex: Female, Male Male	29 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	48 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants
Race (NIH/OMB) White	54 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 3,021 days (up to 14-Jan-2019)

Population: All participants who received ≥1 dose of study drug are included.

Outcome measures

Outcome measures
Measure	Tivantinib (Monotherapy or Combination) n=60 Participants Participants received tivantinib 360 mg twice daily by mouth as monotherapy or combination therapy.
Extent of Exposure to ARQ 197 in Participants Benefiting From Prior ARQ 197 Therapy	125 Days Interval 5.0 to 3021.0

SECONDARY outcome

Timeframe: Up to 3021 days

Population: All participants who received ≥1 dose of study drug are included.

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

Outcome measures

Outcome measures
Measure	Tivantinib (Monotherapy or Combination) n=60 Participants Participants received tivantinib 360 mg twice daily by mouth as monotherapy or combination therapy.
Number of Participants With ≥1 Treatment-emergent Adverse Event (TEAE)	56 Participants

SECONDARY outcome

Timeframe: Up to 3,021 days

Population: All participants who received ≥1 dose of study drug are included.

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

Outcome measures

Outcome measures
Measure	Tivantinib (Monotherapy or Combination) n=60 Participants Participants received tivantinib 360 mg twice daily by mouth as monotherapy or combination therapy.
Number of Participants Discontinuing Treatment Due to an AE	6 Participants

Adverse Events

Tivantinib (Monotherapy or Combination)

Serious events: 19 serious events

Other events: 55 other events

Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure	Tivantinib (Monotherapy or Combination) n=60 participants at risk Participants received tivantinib 360 mg twice daily by mouth as monotherapy or combination therapy.
Blood and lymphatic system disorders Anaemia	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Blood and lymphatic system disorders Febrile neutropenia	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Cardiac disorders Atrial fibrillation	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Cardiac disorders Cardiopulmonary failure	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Gastrointestinal disorders Abdominal mass	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Gastrointestinal disorders Abdominal pain	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Gastrointestinal disorders Diarrhoea	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Gastrointestinal disorders Duodenal ulcer	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Gastrointestinal disorders Nausea	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Gastrointestinal disorders Small intestinal obstruction	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Gastrointestinal disorders Vomiting	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
General disorders Disease progression	3.3% 2/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Hepatobiliary disorders Jaundice cholestatic	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Infections and infestations Bronchitis	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Infections and infestations Gastroenteritis	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Infections and infestations Influenza	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Infections and infestations Pneumonia	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Infections and infestations Sepsis	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Infections and infestations Urinary tract infection	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Injury, poisoning and procedural complications Fractured Sacrum	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Metabolism and nutrition disorders Decreased appetite	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Metabolism and nutrition disorders Dehydration	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Musculoskeletal and connective tissue disorders Pathological fracture	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Nervous system disorders Headache	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Respiratory, thoracic and mediastinal disorders Pulmonary mass	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Respiratory, thoracic and mediastinal disorders Respiratory arrest	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Surgical and medical procedures Radical neck dissection	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Surgical and medical procedures Thrombectomy	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Vascular disorders Aortic stenosis	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Vascular disorders Hypotension	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Vascular disorders Superior vena caval occlusion	1.7% 1/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.

Other adverse events

Other adverse events
Measure	Tivantinib (Monotherapy or Combination) n=60 participants at risk Participants received tivantinib 360 mg twice daily by mouth as monotherapy or combination therapy.
Blood and lymphatic system disorders Anaemia	10.0% 6/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Blood and lymphatic system disorders Neutropenia	11.7% 7/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Blood and lymphatic system disorders Thrombocytopenia	11.7% 7/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Gastrointestinal disorders Abdominal distension	8.3% 5/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Gastrointestinal disorders Abdominal pain	11.7% 7/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Gastrointestinal disorders Constipation	10.0% 6/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Gastrointestinal disorders Diarrhoea	26.7% 16/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Gastrointestinal disorders Dyspepsia	6.7% 4/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Gastrointestinal disorders Nausea	23.3% 14/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Gastrointestinal disorders Vomiting	33.3% 20/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
General disorders Fatigue	28.3% 17/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
General disorders Mucosal inflammation	8.3% 5/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
General disorders Oedema peripheral	11.7% 7/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
General disorders Pain	11.7% 7/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
General disorders Pyrexia	8.3% 5/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Infections and infestations Sinusitis	8.3% 5/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Infections and infestations Upper respiratory tract infection	11.7% 7/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Investigations Weight decreased	13.3% 8/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Metabolism and nutrition disorders Decreased appetite	20.0% 12/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Musculoskeletal and connective tissue disorders Back pain	13.3% 8/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	6.7% 4/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Nervous system disorders Headache	10.0% 6/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Psychiatric disorders Depression	13.3% 8/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Psychiatric disorders Insomnia	10.0% 6/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Respiratory, thoracic and mediastinal disorders Cough	18.3% 11/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Respiratory, thoracic and mediastinal disorders Dyspnoea	18.3% 11/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	8.3% 5/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Skin and subcutaneous tissue disorders Alopecia	10.0% 6/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Skin and subcutaneous tissue disorders Dry skin	10.0% 6/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Skin and subcutaneous tissue disorders Rash	11.7% 7/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	6.7% 4/60 • Up to 3021 days All participants who received ≥1 dose of study drug are included.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Investigator shall have the right to publish the results of research performed under this protocol, provided that such publication does not disclose any confidential information or trade secrets of ArQule (other than the data).
Publication restrictions are in place

Restriction type: OTHER