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2017 ASCO Annual Meeting!


Session: Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics

Type: Poster Session

Time: Monday June 5, 8:00 AM to 11:30 AM

Location: Hall A


Session: Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics

Type: Poster Discussion Session

Time: Monday June 5, 11:30 AM to 12:45 PM

Location: Arie Crown Theater

A phase I study of PT-112 in advanced solid tumors.

Sub-category:
Small Molecules

Category:
Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics

Meeting:
2017 ASCO Annual Meeting

Abstract No:
2519

Poster Board Number:
Poster Discussion Session (Board #11)

Citation:
J Clin Oncol 35, 2017 (suppl; abstr 2519)

Author(s): Daniel D. Karp, D. Ross Camidge, Alan Haruo Bryce, Jose Jimeno, Jeffrey R. Infante; Department of Investigational Cancer Therapeutics (Phase I Program), The University of Texas MD Anderson Cancer Center, Houston, TX; University of Colorado-Denver, Aurora, CO; Mayo Clinic, Phoenix, AZ; Pangaea Biotech SL, Barcelona, Spain; Sarah Cannon Research Institute and Tennessee Oncology, PLLC, Nashville, TN

Abstract Disclosures

Abstract:

Background: PT-112 is a novel platinum-pyrophosphate agent designed to avoid the toxicity and drug resistance mechanisms of conventional chemotherapy. Pre-clinical models show effects on multiple cell signaling components: p16 mediated G1/S cell cycle arrest; modulation of MDM2/p53 expression; extrinsic apoptosis initiation; and immunogenic cell death (ICD) induction. This Phase I first-in-human, multicenter, open label study assesses PT-112’s safety and pharmacokinetic (PK) profile in advanced solid tumor patients (pts), to determine the RP2D and signals of activity. Methods: Pts with advanced solid tumors and acceptable marrow / organ function received PT-112 IV over 1-hr on days 1, 8, and 15 every 4 wks in a 3+3 dose escalation design. Intra-subject escalation was allowed. PK samples from cycles 1-2 were analyzed by ICP-MS and LC-MS/MS. Results: 44 pts have been treated across dose levels (DL) from 12-300mg/m2. Cumulative dosing ranged from 1 to 60 infusions, and cumulative exposure from 96 to 5,244 mg/m2. PK parameters were dose proportional. Target Cmax and AUC levels were achieved, with constant VD. DLTs were observed at 150mg/m2 (G3 pancytopenia); 250mg/m2 (G2 renal injury in a cervical ca pt with hydro-nephrosis); and 300mg/m2 (G3 rash). The most common treatment-related AEs were G1-2 fatigue (26% pts), nausea (23%), vomiting (14%), constipation (12%), and diarrhea (12%). Numerous signals of activity were observed at DLs ≥ 125mg/m2. These include a confirmed PR in a NSCLC pt with 6 prior lines of therapy and no response to TKI inhibition or PD-1 blockade; PFS > 6 months (7-18 months) in 3 pts; metabolic response via PET scan in bone and liver mets (basal cell and pancreatic ca.); biomarker responses in ovarian and prostate ca.; and nodal/metastatic volumetric reduction in 3 pts. Conclusions: PT-112 is a well-tolerated novel agent with a pleiotropic mode of action and feasibility for long-term and combination treatment. Numerous signals of anti-cancer efficacy in heavily pre-treated pts suggest lack of cross-resistance with conventional agents. MTD has not yet been reached. PT-112’s profile makes it an attractive candidate for further development, including in combination with immunotherapy. Clinical trial information: NCT02266745

 
Other Abstracts in this Sub-Category:

 

1. A phase Ib dose escalation study of combined inhibition of IDO1 (GDC-0919) and PD-L1 (atezolizumab) in patients (pts) with locally advanced or metastatic solid tumors.

Meeting: 2017 ASCO Annual Meeting Abstract No: 105 First Author: Howard A. Burris
Category: Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics - Small Molecules

 

2. Debio 1347, an oral FGFR inhibitor: Results from a first-in-human, phase I dose-escalation study in patients with FGFR genomically activated advanced solid tumors.

Meeting: 2017 ASCO Annual Meeting Abstract No: 2500 First Author: Martin Henner Voss
Category: Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics - Small Molecules

 

3. The efficacy of larotrectinib (LOXO-101), a selective tropomyosin receptor kinase (TRK) inhibitor, in adult and pediatric TRK fusion cancers.

Meeting: 2017 ASCO Annual Meeting Abstract No: LBA2501 First Author: David Michael Hyman
Category: Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics - Small Molecules

 

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