On November 11, 2020 Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH), reported the presentation of encouraging preliminary results from the ongoing Phase 1/2 study of DCC-3014, a highly selective, oral, investigational switch-control kinase inhibitor of CSF1R, in patients with tenosynovial giant cell tumor (TGCT) (Press release, Deciphera Pharmaceuticals, NOV 11, 2020, View Source [SID1234570581]). The presentation, titled "Phase 1 Dose-Escalation Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DCC-3014 in Advanced Solid Tumors and Tenosynovial Giant Cell Tumor (TGCT)", will be presented at the CTOS 2020 Virtual Annual Meeting, being held November 18-21, 2020. Posters and presentations are available to meeting participants as of November 11, 2020.

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"We are very encouraged by the updated data in additional TGCT patients from the ongoing Phase 1/2 study of DCC-3014," said Matthew L. Sherman, MD, Executive Vice President and Chief Medical Officer of Deciphera. "The preliminary results presented in TGCT patients at the CTOS 2020 Virtual Annual Meeting demonstrated highly encouraging evidence of anti-tumor activity, and DCC-3014 was shown to be generally well-tolerated. These results further support the evaluation of DCC-3014 in patients with TGCT and bolster our confidence in its potential to make a meaningful impact in this disease, which is typically associated with progressively reduced mobility and function. We have selected the recommended Phase 2 dose and initiated the TGCT expansion cohorts to further evaluate the safety and efficacy of DCC-3014."

"TGCT is a rare and debilitating disease that is most often treated with surgery," said William D. Tap, MD, Chief of the Sarcoma Medical Oncology Service at Memorial Sloan Kettering Cancer Center in New York. "Despite the best surgical intervention, the disease may advance to the point where surgery is no longer an option, and so there remains a need for effective, well-tolerated systemic therapies to help these patients. These preliminary results demonstrate that DCC-3014 has the potential to be a safe and effective treatment option for TGCT patients."

The Company’s international, multicenter, open-label Phase 1/2 study of DCC-3014 was designed to evaluate the safety, efficacy, pharmacokinetics, and pharmacodynamics of DCC-3014 in patients with malignant solid tumors and TGCT. Data presented at the CTOS 2020 Virtual Annual Meeting are from 25 TGCT patients enrolled in the dose-escalation portion of the Phase 1/2 study. The cutoff date for the safety data was September 23, 2020, and the cutoff date for the efficacy data was October 5, 2020.

Preliminary results from DCC-3014 in TGCT patients:

Dose Cohorts and Demographics

25 TGCT patients enrolled in the study in three dose cohorts:
Cohort 5 (n=7): 30 mg loading dose daily for five days followed by a maintenance dose of 30 mg twice a week;
Cohort 8 (n=12): 30 mg loading dose daily for three days followed by a maintenance dose of 10 mg daily; and
Cohort 9 (n=6): 20 mg loading dose daily for three days followed by a maintenance dose of 6 mg daily.
Seven patients (28%) had at least one prior surgery and four patients (16%) had received at least one prior systemic therapy.
Preliminary Efficacy and Duration of Treatment

22 patients were evaluable for efficacy by RECIST v1.1 at the data cutoff with central assessment available for 21 of the 22 patients; three patients had not yet reached first efficacy assessment.
Objective response rate of 41%.
Nine of 22 patients achieved an objective response, including one complete response.
Of the nine responses, three were confirmed and six are awaiting confirmation.
78% of responders (7 of 9 patients) had a partial response at their first restaging scan at Cycle 3 Day 1 (week 9).
22 of 25 patients were receiving treatment with DCC-3014 at the data cutoff. Two patients withdrew from the study and one patient discontinued due to an adverse event.
Two TGCT patients were on treatment for 12 or more months with responses that deepened over time.
Safety and Tolerability

Treatment with DCC-3014 was generally well-tolerated in patients with TGCT not amenable to surgery. One patient (4%) discontinued treatment due to an adverse event (asymptomatic Grade 3 AST elevation, from Grade 1 at baseline).
Treatment-emergent adverse events (TEAEs) (mostly grade 1/2) occurring in ≥25% of patients with TGCT regardless of relatedness were blood creatine phosphokinase (CPK) increased (52%), aspartate amino transferase (AST) increased (44%), periorbital edema (44%), fatigue (40%), lipase increased (32%), and alanine aminotransferase (ALT) increased (28%). No serious adverse events related to DCC-3014 were reported.
All bilirubin levels were within the normal limit.
Observed transaminase and pancreatic enzyme elevations were asymptomatic and not clinically significant.
Pharmacokinetics, Pharmacodynamics and Recommended Phase 2 Dose

Similar steady state pharmacokinetic profiles were observed between the 30 mg twice weekly (cohort 5) and 10 mg daily (cohort 8) dosing regimens; lower exposure was observed in the 6 mg daily (cohort 9) dosing regimen.
Across all cohorts, DCC-3014 treatment resulted in an increase in plasma CSF1/IL-34 and a decrease in non-classical sub-type of monocytes, indicating pharmacodynamic inhibition of CSF1R.
The recommended Phase 2 dose for DCC-3014 in TGCT patients was determined to be 30 mg twice weekly (no loading dose).
Based on these encouraging results, the Phase 1/2 study of DCC-3014 is ongoing and enrolling up to 60 patients into two expansion cohorts, one for TGCT patients with no prior exposure to anti-CSF1/CSF1R agents (n=40) and a second for patients with prior exposure to anti-CSF1/CSF1R agents (n=20). In addition, enrollment of an additional six patients in cohort 9 of the dose escalation portion of the study is ongoing to complete enrollment in this cohort.

About Tenosynovial Giant Cell Tumor (TGCT)
TGCT is a rare disease caused by a translocation in colony-stimulating factor 1 (CSF1) gene resulting in overexpression of CSF1 and recruitment of colony-stimulating factor 1 receptor (CSF1R)-positive inflammatory cells into the lesion. TGCT is also known as giant cell tumor of the tendon sheath (GCT-TS) or pigmented villonodular synovitis (PVNS), a diffuse-type of TGCT. Although benign, these tumors can grow and cause damage to surrounding tissues and structures inducing pain, swelling, and limitation of movement of the joint. Surgery is the main treatment option; however, these tumors tend to recur, particularly in diffuse-type TGCT. If untreated or if the tumor continually recurs, damage and degeneration may occur in the affected joint and surrounding tissues, which may cause significant disability.

About DCC-3014
DCC-3014 is an investigational, orally administered, potent and highly selective switch-control kinase inhibitor of CSF1R. DCC-3014 was designed using the Company’s proprietary discovery platform to selectively bind to the CSF1R switch pocket. Through inhibition of CSF1R, DCC-3014 has demonstrated encouraging preliminary efficacy and safety data in tenosynovial giant cell tumor (TGCT) and is currently being evaluated in a Phase 1/2 clinical study. For more information about the clinical trial design, please visit www.clinicaltrials.gov (NCT03069469).