Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Tivantinib
ARQ 197 · 11 trials · 13 indications
Overall survival (OS) is defined as the time from randomization to the date of death. The rate of OS (percentage of participants still alive) was determined only in the tivantinib 120 mg BID cohort.
Overall survival (OS) is defined as the time from randomization to the date of death. The rate of OS (percentage of participants still alive) was determined only in the tivantinib 120 mg BID cohort.
Progression is defined using Response Evaluation Criteria in Solid Tumors (RECIST v 1.1) criteria as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum 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 or progression of existing non-target lesions are also considered progression.
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).
| Arm | Type | Description |
|---|---|---|
| Tivantinib 240 mg BID Cohort | EXPERIMENTAL | The tivantinib dosage of 240 mg tablets administered by mouth twice daily (BID), once in the morning and once in the evening, with food, for a total daily dose of 480 mg. |
| Tivantinib 120 mg BID Cohort | EXPERIMENTAL | Tivantinib 120 mg is administered by oral tablet BID, once in the morning and once in the evening, with food, for a total daily dose of 240 mg (amended dosing group; primary analysis group). |
| Placebo Matching 240 mg BID Cohort | PLACEBO_COMPARATOR | Matching placebo is administered by oral tablet(s) BID, once in the morning and once in the evening, with food. |
| Placebo Matching 120 mg BID Cohort | PLACEBO_COMPARATOR | Matching placebo is administered by oral tablet(s) BID, once in the morning and once in the evening, with food. |
| tivantinib (ARQ 197) plus erlotinib arm | EXPERIMENTAL | Eligible subjects will be randomly assigned to receive erlotinib plus tivantinib (ARQ 197). Treatment will be open-label and continue until progression of disease, unacceptable toxicity, or another discontinuation criterion is met. |
| Chemotherapy arm | ACTIVE_COMPARATOR | Investigator's choice of single agent chemotherapy (pemetrexed, docetaxel, or gemcitabine) administered in 3-week cycles according to the approved label until disease progression or unacceptable toxicity. Subjects who discontinued chemotherapy can be switched to the crossover arm (tivantinib plus erlotinib) and continue treatment until disease progression or unacceptable toxicity. |
| ARQ 197 | EXPERIMENTAL | - |
| placebo | PLACEBO_COMPARATOR | - |
| 1 | EXPERIMENTAL | Erlotinib (150 mg) once daily plus ARQ 197 (360 mg) twice daily. |
| 2 | ACTIVE_COMPARATOR | Erlotinib (150 mg) once daily plus ARQ 197 placebo twice daily |
| Tivantinib (Monotherapy or Combination Therapy) | EXPERIMENTAL | Tivantinib 360 mg will be administered twice daily, orally, with meals, as a monotherapy or in combination with other drug therapies. |
| Name | Type | Description |
|---|---|---|
| Tivantinib | DRUG | Tivantinib tablets |
| Placebo | DRUG | Matching placebo tablets |
| ARQ 197 plus erlotinib | DRUG | Eligible subjects will be randomly assigned to receive erlotinib plus ARQ 197. |
| Pemetrexed, docetaxel or gemcitabine | DRUG | Investigator's choice of a single agent chemotherapy (pemetrexed, docetaxel, or gemcitabine) administered according to the approved label. |
| ARQ 197 | DRUG | The investigational drug ARQ 197 is supplied as capsules. A dose of 360 mg (3 capsules of 120 mg each) of ARQ 197 will be administered by mouth BID, once in the morning and once in the evening with meals, for a total daily dose of 720 mg. Under Amendment 2, a dose of 240 mg (2 capsules of 120 mg each) of ARQ 197/placebo will be administered by mouth BID, once in the morning and once in the evening with meals, for a total daily dose of 480 mg. A treatment cycle is defined as 4 weeks for both treatment arms. Cycles will be repeated every 4 weeks (28 days) based on toxicity and response. |
| Erlotinib | DRUG | Erlotinib is a white, film coated tablet in strengths of 25, 100 and 150 mg administered once daily until disease progression, unacceptable toxicity or other discontinuation criterion is met. |
| gemcitabine | DRUG | 1000 mg/m2 administered as an intravenous infusion over 30 minutes once weekly for 4 weeks for the first 28 days (cycle). Each subsequent cycle will consist of 1000 mg/m2 administered as an intravenous infusion over 30 minutes once weekly for 3 weeks with no drug administered in the 4th week. |
| Anti-Cancer Combination Therapy | DRUG | Tivantinib 360 mg twice daily in combination with other anti-cancer therapy (eg, erlotinib,sorafenib, pemetrexed, docataxel, gemcitabine, irinotecan, and/or cetuximab) at the same dose and schedule in which they were administered in the original (previous) study. |
Inclusion Criteria: * Histologically confirmed HCC that is inoperable (where surgery is not indicated due to disease extension, co-morbidities, or other technical reasons), and not eligible for local therapy * MET Diagnostic-High tissue reported by the central authorized laboratory using archival o...
Top 20 of 90 competitors
ARQ 197 is an investigational small molecule cancer drug developed by Merck & Company, Inc. (MRK). It has been studied in advanced solid tumors and several cancer types, including non-small cell lung cancer, hepatocellular carcinoma, pancreatic neoplasms, and in patients with cirrhosis. It is not described as approved and remains in clinical development.
ARQ 197 has been studied in non-small cell lung cancer, including locally advanced or metastatic disease. Trials combined it with erlotinib, an EGFR inhibitor, and compared that combination with single agent chemotherapy or with erlotinib plus placebo in previously treated patients. These studies are complete, and ARQ 197 is not an approved treatment.
Merck & Company, Inc., which trades under the ticker MRK, is the developer of ARQ 197. The company sponsored the clinical trials of the drug in non-small cell lung cancer, hepatocellular carcinoma, and cirrhotic patients with hepatocellular carcinoma.
ARQ 197 is in Phase 1 development according to its current development stage, and it is investigational rather than approved. Its clinical program has included Phase 1 and Phase 2 studies, all of which are completed, with no active trials currently listed.
ARQ 197 has been evaluated in completed trials including NCT01395758, NCT00988741, NCT00802555, and NCT00777309. These studies covered metastatic non-small cell lung cancer, unresectable hepatocellular carcinoma, and cirrhotic patients with hepatocellular carcinoma, and enrolled a combined total of 167 participants in the reported trial set.