Trial Outcomes & Findings for ARQ 197 for Participants With Relapsed or Refractory Germ Cell Tumors (NCT NCT01055067)

Last Updated: 2021-04-06

Results Overview

The best overall response was the best response (in the order of confirmed complete response \[CR\], confirmed partial response \[PR\], unconfirmed CR, unconfirmed PR, stable disease \[SD\], and progressive disease \[PD\]) among all overall responses recorded from the start of treatment until the participant withdrew from the study. Objective response was defined as the number of participants with confirmed CR and confirmed PR after 4 cycles of therapy with ARQ 197. According to Response Evaluation Criteria in Solid Tumors v 1.1, CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, defined as at least a 20% increase in the sum of diameters of target lesions.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

27 participants

Primary outcome timeframe

Baseline up to first objective response, up to 1 year 9 months postdose

Results posted on

2021-04-06

Participant Flow

A total of 27 participants who met all inclusion and no exclusion criteria were enrolled and treated at 7 clinic sites in the United States, 2 in France, and 2 in the United Kingdom. Of the 27 enrolled, 21 were included in Stage 1 in which the interim futility analysis was performed per the Simon 2-stage design.

Based on the Simon 2-stage design, 21 participants were enrolled (Stage 1). If \<2 had either a complete response (CR) or partial response (PR), then the study was terminated. If ≥2 had either CR or PR, then enrollment was extended to 41 participants. After Stage 2 with 41 participants, treatment was effective if ≥5 had CR or PR after 4 cycles.

Participant milestones

Participant milestones
Measure	Total All enrolled participants who received at least 1 dose of study drug in the study.
Overall Study STARTED	27
Overall Study COMPLETED	27
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

ARQ 197 for Participants With Relapsed or Refractory Germ Cell Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Total n=27 Participants All enrolled participants who received at least 1 dose of study drug in the study.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	27 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	33.0 years STANDARD_DEVIATION 11.59 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	27 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	23 Participants n=5 Participants
Race/Ethnicity, Customized Other	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to first objective response, up to 1 year 9 months postdose

Population: Objective response rate was assessed in the Full Analysis Set.

Outcome measures

Outcome measures
Measure	Stage 1: ARQ 197 360 mg BID n=21 Participants Participants who were enrolled in Stage 1 of the Simon 2-stage design and received ARQ 197 360 mg twice a day (BID) (with a 720 mg total daily dose) in participants with relapsed or refractory non-central nervous system germ cell tumor (non-CNS GCT).	Total n=27 Participants All enrolled participants who received at least 1 dose of study drug in the study.
Best Overall Response and Objective Response Rate Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors Confirmed CR	0 Participants	0 Participants
Best Overall Response and Objective Response Rate Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors Confirmed PR	0 Participants	0 Participants
Best Overall Response and Objective Response Rate Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors Stable disease	3 Participants	5 Participants
Best Overall Response and Objective Response Rate Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors Progressive disease	16 Participants	20 Participants
Best Overall Response and Objective Response Rate Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors Objective response rate	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline up to progressive disease or death (whichever occurs first), up to 1 year 9 months postdose

Population: Progression-free survival was assessed in the Full Analysis Set.

Progression-free survival (PFS) is defined as the time from the date of the start of study treatment to the earlier of the dates of the first documentation of progressive disease (PD) or death due to any cause. According to Response Evaluation Criteria in Solid Tumors v 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.

Outcome measures

Outcome measures
Measure	Stage 1: ARQ 197 360 mg BID n=21 Participants Participants who were enrolled in Stage 1 of the Simon 2-stage design and received ARQ 197 360 mg twice a day (BID) (with a 720 mg total daily dose) in participants with relapsed or refractory non-central nervous system germ cell tumor (non-CNS GCT).	Total n=27 Participants All enrolled participants who received at least 1 dose of study drug in the study.
Progression-Free Survival Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors	4.3 weeks Interval 4.1 to 8.0	4.3 weeks Interval 4.1 to 8.0

SECONDARY outcome

Timeframe: Baseline up to death (any cause), up to 1 year 9 months postdose

Population: Overall survival was assessed in the Full Analysis Set.

Overall survival (OS) was defined as the time from the date of the start of study treatment to the date of death due to any cause.

Outcome measures

Outcome measures
Measure	Stage 1: ARQ 197 360 mg BID n=21 Participants Participants who were enrolled in Stage 1 of the Simon 2-stage design and received ARQ 197 360 mg twice a day (BID) (with a 720 mg total daily dose) in participants with relapsed or refractory non-central nervous system germ cell tumor (non-CNS GCT).	Total n=27 Participants All enrolled participants who received at least 1 dose of study drug in the study.
Overall Survival Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors	6.2 months Interval 3.5 to 7.7	5.9 months Interval 3.5 to 7.7

SECONDARY outcome

Timeframe: Baseline up to 30 days after last dose, up to 1 year 9 months postdose

Population: Adverse events were assessed in the Safety Analysis Set.

Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the first dose until 30 days after the last dose.

Outcome measures

Outcome measures
Measure	Stage 1: ARQ 197 360 mg BID n=21 Participants Participants who were enrolled in Stage 1 of the Simon 2-stage design and received ARQ 197 360 mg twice a day (BID) (with a 720 mg total daily dose) in participants with relapsed or refractory non-central nervous system germ cell tumor (non-CNS GCT).	Total n=27 Participants All enrolled participants who received at least 1 dose of study drug in the study.
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors Any TEAEs	19 Participants	25 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors Gastrointestinal Disorders	8 Participants	11 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors Constipation	2 Participants	3 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors Nausea	6 Participants	7 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors Vomiting	4 Participants	4 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors General Disorders & Administration Site Conditions	12 Participants	15 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors Fatigue	7 Participants	10 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors Edema peripheral	3 Participants	4 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors Metabolism and Nutrition Disorders	3 Participants	6 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors Decreased appetite	3 Participants	4 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors Musculoskeletal and Connective Tissue Disorders	4 Participants	6 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors Back pain	2 Participants	3 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors Nervous System Disorders	7 Participants	11 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors Neuropathy peripheral	3 Participants	3 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors Respiratory, Mediastinal, and Thoracic Disorders	8 Participants	12 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors Cough	3 Participants	6 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors Dyspnea	4 Participants	6 Participants

Adverse Events

Stage 1: ARQ 197 360 mg BID

Serious events: 6 serious events

Other events: 11 other events

Deaths: 0 deaths

Total

Serious events: 9 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Stage 1: ARQ 197 360 mg BID n=21 participants at risk Participants who were enrolled in Stage 1 of the Simon 2-stage design and received ARQ 197 360 mg twice a day (BID) (with a 720 mg total daily dose) in participants with relapsed or refractory non-central nervous system germ cell tumor (non-CNS GCT).	Total n=27 participants at risk All enrolled participants who received at least 1 dose of study drug in the study.
Blood and lymphatic system disorders Anaemia	0.00% 0/21 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 30 days after last dose, up to 1 year 9 months. Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the first dose until 30 days after the last dose.	3.7% 1/27 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 30 days after last dose, up to 1 year 9 months. Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the first dose until 30 days after the last dose.
Eye disorders Vision blurred	4.8% 1/21 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 30 days after last dose, up to 1 year 9 months. Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the first dose until 30 days after the last dose.	3.7% 1/27 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 30 days after last dose, up to 1 year 9 months. Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the first dose until 30 days after the last dose.
Gastrointestinal disorders Peritoneal haemorrhage	0.00% 0/21 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 30 days after last dose, up to 1 year 9 months. Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the first dose until 30 days after the last dose.	3.7% 1/27 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 30 days after last dose, up to 1 year 9 months. Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the first dose until 30 days after the last dose.
Immune system disorders Hypersensitivity	4.8% 1/21 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 30 days after last dose, up to 1 year 9 months. Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the first dose until 30 days after the last dose.	3.7% 1/27 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 30 days after last dose, up to 1 year 9 months. Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the first dose until 30 days after the last dose.
Infections and infestations Cellulitis	4.8% 1/21 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 30 days after last dose, up to 1 year 9 months. Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the first dose until 30 days after the last dose.	3.7% 1/27 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 30 days after last dose, up to 1 year 9 months. Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the first dose until 30 days after the last dose.
Infections and infestations Pneumonia	4.8% 1/21 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 30 days after last dose, up to 1 year 9 months. Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the first dose until 30 days after the last dose.	3.7% 1/27 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 30 days after last dose, up to 1 year 9 months. Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the first dose until 30 days after the last dose.
Musculoskeletal and connective tissue disorders Back pain	4.8% 1/21 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 30 days after last dose, up to 1 year 9 months. Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the first dose until 30 days after the last dose.	3.7% 1/27 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 30 days after last dose, up to 1 year 9 months. Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the first dose until 30 days after the last dose.
Nervous system disorders Cerebral haemorrhage	0.00% 0/21 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 30 days after last dose, up to 1 year 9 months. Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the first dose until 30 days after the last dose.	3.7% 1/27 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 30 days after last dose, up to 1 year 9 months. Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the first dose until 30 days after the last dose.
Nervous system disorders Headache	4.8% 1/21 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 30 days after last dose, up to 1 year 9 months. Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the first dose until 30 days after the last dose.	3.7% 1/27 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 30 days after last dose, up to 1 year 9 months. Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the first dose until 30 days after the last dose.
Nervous system disorders Sciatica	0.00% 0/21 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 30 days after last dose, up to 1 year 9 months. Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the first dose until 30 days after the last dose.	3.7% 1/27 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 30 days after last dose, up to 1 year 9 months. Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the first dose until 30 days after the last dose.
Nervous system disorders Spinal cord compression	4.8% 1/21 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 30 days after last dose, up to 1 year 9 months. Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the first dose until 30 days after the last dose.	3.7% 1/27 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 30 days after last dose, up to 1 year 9 months. Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the first dose until 30 days after the last dose.
Vascular disorders Superior vena caval occlusion	4.8% 1/21 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 30 days after last dose, up to 1 year 9 months. Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the first dose until 30 days after the last dose.	3.7% 1/27 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 30 days after last dose, up to 1 year 9 months. Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the first dose until 30 days after the last dose.

Other adverse events

Additional Information

Contact for Clinical Trial Information

Daiichi Sankyo

Phone: 908-992-6400

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place