Virtual Library
Start Your Search
T.M. Bauer
Author of
-
+
OA05 - Treatment Advances in SCLC (ID 373)
- Event: WCLC 2016
- Type: Oral Session
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:A. Ardizzoni, J. Pujol
- Coordinates: 12/05/2016, 14:20 - 15:50, Strauss 2
-
+
OA05.03 - Single-Agent Rovalpituzumab Tesirine, a Delta-Like Protein 3 (DLL3)-Targeted Antibody-Drug Conjugate (ADC), in Small-Cell Lung Cancer (SCLC) (ID 4648)
14:40 - 14:50 | Author(s): T.M. Bauer
- Abstract
- Presentation
Background:
SCLC is one of the most deadly malignancies. Rovalpituzumab tesirine (SC16LD6.5, Rova-T) is a first-in-class ADC directed against DLL3, a novel target identified in tumor initiating cells and expressed in over 80% of SCLC cases.
Methods:
Seventy-four patients with progressive SCLC after at least one previous systemic therapy were enrolled in a first-in-human study (NCT01901653), irrespective of DLL3 expression, including 68 at active doses of 0.2-0.4 mg/kg administered intravenously every 3 or 6 weeks. Available archived tumor tissue (n=48) was assessed retrospectively by immunohistochemistry for DLL3.
Results:
Among 60 evaluable subjects, active dose levels resulted in a confirmed objective response rate (ORR) of 18% and a confirmed clinical benefit rate (CBR; stable disease or better) of 68%. Among 26 evaluable subjects with DLL3 expression in at least 50% of tumor cells (DLL3-high), confirmed ORR and CBR were 39% and 89%, respectively. Median duration of response was 5.6 months. One-year survival rates among all and DLL3-high subjects were 18% and 32%, respectively. Among primary sensitive relapse patients, confirmed ORR and CBR among all subjects were 24% (8/33) and 67% (22/33); and among DLL3-high subjects were 53% (8/15) and 100% (15/15), with one-year survival rates of 17% and 33%, respectively. Among primary resistant/refractory relapse patients, confirmed ORR and CBR among all subjects were 12% (3/25) and 72% (18/25); and among DLL3-high subjects were 18% (2/11) and 73% (8/11), with one-year survival rates of 21% and 29%, respectively. The most common grade 3 or higher toxicities included thrombocytopenia (12%), serosal effusions (11%), and skin reactions (8%). ADC pharmacokinetics were linear with a terminal half-life of 10 - 14 days and anti-therapeutic antibodies did not develop
Conclusion:
Rovalpituzumab tesirine demonstrates encouraging single-agent anti-tumor activity with a manageable safety profile, including among patients with disease resistant or refractory to primary chemotherapy. Further development of rovalpituzumab tesirine in SCLC is warranted.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
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: 2
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
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): T.M. Bauer
- 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
-
+
P2.06-011 - Phase 2 Study of MM-121 plus Chemotherapy vs. Chemotherapy Alone in Heregulin-Positive, Locally Advanced or Metastatic NSCLC (ID 4158)
14:30 - 14:30 | Author(s): T.M. Bauer
- Abstract
Background:
The role of the HER3 receptor and its ligand heregulin (HRG) in the progression of multiple cancers has been well established. Seribantumab (MM-121) is a fully human, monoclonal IgG2 antibody that binds to the HRG domain of HER3, blocking HER3 activity. The correlation between the level of HRG mRNA in tumor tissue and progression free survival (PFS) were retrospectively analyzed in three completed randomized Phase 2 studies of seribantumab plus standard of care (SOC) versus SOC alone (NSCLC, breast cancer and ovarian cancer). In each of these studies, high levels of HRG mRNA predicted shortened PFS for patients who received SOC treatment, while the addition of seribantumab to SOC improved PFS for patients with HRG-positive (HRG+) tumors. This is consistent with the hypothesis that HRG expression defines a drug tolerant cancer cell phenotype shielded from the effects of cytotoxic or targeted therapies and that blockade of HRG-induced HER3 signaling by seribantumab counters the effects of HRG on cancer cells, with the potential to improve outcomes for HRG+ patients. It is estimated that up to approximately 50% of cases of all solid tumor indications are HRG+. This HRG expression may contribute to rapid clinical progression in a subset of patients with poor prognosis.
Methods:
In the ongoing randomized, open-label, international, Phase 2 study, NSCLC patients with HRG+ tumors are being prospectively selected using a HRG RNA in situ hybridization assay performed on a recent tumor tissue sample collected via fine needle aspiration, core needle biopsy or excision. Approximately 560 patients will be screened to support enrollment of 280 HRG+ patients, who will be randomized in a 2:1 ratio to receive seribantumab plus investigator’s choice of docetaxel or pemetrexed, or docetaxel or pemetrexed alone. Patients will be wild-type for EGFR and ALK and will have progressed following one to three systemic therapies, one of which must be an anti-PD-1 or anti-PD-L1 therapy, for locally advanced and/or metastatic disease. Overall survival (OS) is the primary endpoint of the study and secondary endpoints include PFS, objective response rate and time to progression. Safety and health-related quality of life will also be assessed. An interim analysis is planned when 50% of final OS events have been reported. Enrollment has been initiated with approximately 80 sites expected to participate worldwide. Clinical Trials Registry number: NCT02387216
Results:
Section not applicable
Conclusion:
Section not applicable
