A Phase 1 Dose Escalation Study of ARQ 197 in Combination With Sorafenib in Adult Patients With Advanced Solid Tumors
The study is only enrolling patients in the expanded cohorts with hepatocellular carcinoma,
renal cell carcinoma, melanoma, non-small cell lung cancer, and breast cancer.
Enrollment of an initial patient cohort of 3 or 6 patients will follow the traditional "3 +
3" dose escalation scheme. These patients will be treated with ARQ 197 and sorafenib at
Dose Level 1 (ARQ 197 360 mg BID and sorafenib 200 mg BID). Enrollment of subsequent
patient cohort(s) will depend on the safety and tolerability of the combination treatment in
the initial cohort. If <33% patients treated at Dose Level 1 experience dose-limiting
toxicity(ies) (DLT) by the end of first treatment cycle (4 weeks), then next cohort of 6
patients will be enrolled and treated at Dose Level 2 (ARQ 197 360 mg BID and sorafenib 400
mg BID). If ≥ 33% patients treated at Dose Level 1 experience DLT(s) by the end of first
treatment cycle, the next cohort of 6 patients will be enrolled and treated at Dose Level 0
(ARQ 197 240 mg BID and sorafenib 200 mg BID).
Additional treatment cohorts may be enrolled to explore intermediate, higher or lower doses
of ARQ 197, as indicated by the tolerability, safety profile, and pharmacokinetic (PK)
Intra-patient dose-escalation from Dose Level 1 to Dose Level 2 may occur in patients
enrolled in Dose Level 1 after they complete at least 1 cycle of treatment without DLT and
other drug-related adverse event that, in the opinions of Investigator and Medical Monitor,
is serious and medically significant.
Once a safe and recommended dose level is determined, an expanded cohort (Expansion Cohort
1) of up to 40 patients with either unresectable HCC or advanced renal cell carcinoma (RCC),
for whom sorafenib is indicated, will be enrolled and treated at this dose level (expansion
portion). Up to 20 patients with unresectable HCC and up to 20 patients with advanced RCC
may be enrolled in this protocol (including patients in dose-escalation cohorts and
An additional expansion cohort (Expansion Cohort 2) of up to 40 patients with breast cancer,
non-small cell lung cancer or melanoma will be enrolled and treated at MTD/RP2D. Up to 10
patients may be enrolled for breast and non-small cell lung cancer and up to 20 patients
with melanoma (at least 10 of whom must have NRAS mutation).
Under Amendment #3, newly enrolled subjects with HCC will be given ARQ 197 at 240 mg BID as
starting dose. If a patient with HCC tolerates this starting dose for at least one cycle,
the investigator may increase his/her dose to 360 mg BID.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To identify maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of ARQ 197 when administered in combination with sorafenib.
6 to 9 months. Patients will remain on study until progression of disease, unacceptable toxicity, or other discontinuation criterion is met.
United States: Food and Drug Administration
|Roswell Park Cancer Institute||Buffalo, New York 14263|
|Nashville, Tennessee 37203-1632|