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D. Wang
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P2.06 - Poster Session with Presenters Present (ID 467)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.06-001 - A Study of MGCD516, a Receptor Tyrosine Kinase (RTK) Inhibitor, in Molecularly Selected Patients with NSCLC or Other Advanced Solid Tumors (ID 4109)
14:30 - 14:30 | Author(s): D. Wang
- Abstract
Background:
MGCD516 (Sitravatinib), is an oral, potent small molecule inhibitor of a closely related spectrum of RTKs including RET, the split RTKs (VEGFR, PDGFR and KIT), TRK family, DDR2, MET and AXL. RTKs inhibited by sitravatinib are genetically altered in NSCLC and other cancers, where they function as oncogenic drivers, promoting cancer development and progression. Alterations in these RTKs have also been implicated in tumor resistance mechanisms. Sitravatinib has demonstrated antitumor activity in nonclinical cancer models harboring genetic alterations of sitravatinib targets, including rearrangement of RET, NTRK, or CHR4q12 amplification. Phase 1 dose escalation has been completed, showing dose proportional increases in exposure. PK and preliminary PD data indicate inhibition of the targets at the 150 mg dose administered orally once per day.
Methods:
This phase 1b study includes enrollment of molecularly selected patients (pts) with unresectable or metastatic NSCLC or other advanced solid tumor malignancies in patient cohorts characterized by activating alterations in sitravatinib RTK targets (RET, KDR, PDGFRA, KIT, TRK, DDR2, MET, AXL) or by loss of function mutations in CBL, a negative regulator for MET, AXL and PDGFR/KIT signaling. Pts receive sitravatinib at 150 mg once daily in 21-day cycles. Study endpoints include safety and tolerability, PK/PD, and clinical activity assessed by objective disease response per RECIST 1.1, duration of response and survival. A two stage optimal Simon design of up to 24 pts (8 pts in first stage and 16 pts in second stage) will be applied to those cohorts defined by a specific tumor gene alteration assuming p~0~=0.15 and p~1~=0.35, with an additional expansion of a cohort up to a total of 70 pts in order to provide a more precise estimate of ORR. PD biomarkers, including sMET, sVEGFR2, VEGFA and sAXL, are being explored in plasma samples for prognostic potential and possible relationship with clinical outcome. The study is open for enrollment, and recruitment is ongoing. Clinical trial information: NCT02219711
Results:
Section not applicable
Conclusion:
Section not applicable
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P3.02c - Poster Session with Presenters Present (ID 472)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02c-027 - Phase I and PK Study of the Folate Receptor-Targeted Small Molecule Drug Conjugate (SMDC) EC1456 in Advanced Cancer: Lung Cancer Subset (ID 5202)
14:30 - 14:30 | Author(s): D. Wang
- Abstract
Background:
EC1456 is composed of folic acid conjugated through a releasable linker system to a potent microtubule inhibitor, tubulysin B hydrazide. EC1456 targets folate receptor (FR)-expressing cancer cells, which occur in approximately 60% of NSCLC cases and 14% of SCLC.
Methods:
The objectives of the ongoing Phase 1 are to determine the safety, PK, and optimal dosing schedule of EC1456 in advanced cancer pts. FR expression (not required for enrollment) is characterized in all pts using [99m]Tc-etarfolatide.
Results:
63 pts were dosed weekly (QW) or twice-weekly (BIW), for 2 consecutive weeks of a 3-week cycle. 8 NSCLC and 3 SCLC pts received doses ranging from 1.0-12.5 mg/m[2]. Toxicities are primarily Grade (Gr) 1 and 2. Common adverse events (AE) are GI, fatigue, and metabolic changes. Gr 3 infusion reaction (4.5 mg/m[2]) and Gr 3 headache (10.0 mg/m[2]) were seen in the QW cohort. The safety profile in lung cancer pts was similar to the overall population.
Response and durability of response is demonstrated in the figure: Figure 1BIW (N=32) QW (N=31) BIW Lung (N=4) QW Lung (N=7) All Drug Related All Drug Related All Drug Related All Drug Related ≥ 1 AE 32 (100%) 25 (78%) 29 (94%) 23 (74%) 4 (100%) 4 (100%) 7 (100%) 4 (57%) ≥ 1 grade 3 or 4 AE 19 (59%) 6 (19%) 14 (45%) 4 (13%) 2 (50%) 0 (0%) 1 (14%) 0 (0%) ≥ 1 serious AE 12 (38%) 2 (6%) 14 (45%) 5 (16%) 1 (25%) 0 (0%) 2 (29%) 0 (0%) Serious drug related AEs Constipation (2/63 pts); Abd pain, Anemia, Headache, Infusion reactions, and SVT(1/63 pts each)
Conclusion:
EC1456 is well tolerated, with early indications of efficacy suggested by durable stable disease, and responses in this refractory population. Updated safety, PK, and efficacy data will be presented at the meeting.
