Targeted therapy for gastrointestinaI (GI) tumors based on molecular profiles: Early results from MyPathway, an open-label phase IIa basket study in patients with advanced solid tumors.

653 Background: Next-generation sequencing often reveals potentially actionable molecular alterations; however, data on approved targeted therapies in non-indicated tumors are limited. MyPathway (NCT02091141) evaluates agents targeting the HER2, EGFR, BRAF, or Hedgehog (Hh) pathways in tumors for which these therapies are not currently indicated. Here, we present early response data for patients with GI tumors. Methods: Eligible patients had metastatic tumors with potentially actionable genomic alterations, identified by a CLIA-certified lab, and progression on standard therapy. Based on the identified alteration, patients received standard doses of trastuzumab + pertuzumab (HER2), erlotinib (EGFR), vemurafenib (BRAF), or vismodegib (Hh). Response was evaluated by the investigator using RECIST v1.1. Results: As of Aug 21, 2015, 96 patients had enrolled, 36 of whom (38%) had GI tumors with the following alterations: HER2 (n=28 [22 amplifications, 5 activating mutations, 1 both]), BRAF (n=4), Hh (n=2 [2 PTCH-1 mutations]), and EGFR (n=2). Patients had a median of 4 (range, 1–8) prior lines of therapy. Tumor types and interim best response data are shown below. Among all evaluable patients with GI tumors (n=26), 5 have had a PR to targeted therapy (duration 3–10+ months). Conclusions: Targetable molecular alterations were found in a variety of GI tumors, resulting in clinical benefit from targeted treatments that would not have otherwise been realized. These early results support this molecular testing strategy. Accrual to the trial continues; based on activity observed, the HER2-positive colorectal cancer cohort will be expanded to ≥30 patients. Additional data will be presented at the meeting. Clinical trial information: NCT02091141. [Table: see text]

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Targeted therapy for advanced solid tumors based on molecular profiles: Early results from MyPathway, an open-label, phase IIa umbrella basket study.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.18_suppl.lba11511 ◽

2016 ◽

Vol 34 (18_suppl) ◽

pp. LBA11511-LBA11511 ◽

Cited By ~ 4

Author(s):

John D. Hainsworth ◽

Funda Meric-Bernstam ◽

Charles Swanton ◽

Herbert Hurwitz ◽

David R. Spigel ◽

...

Keyword(s):

Targeted Therapy ◽

Solid Tumors ◽

Current Response ◽

Advanced Solid Tumors ◽

Open Label ◽

Curative Therapy ◽

Molecular Alterations ◽

Early Results ◽

Open Label Phase ◽

Tumor Types

LBA11511 Background: The MyPathway study (NCT02091141) evaluates agents targeting the HER2, BRAF, Hedgehog (Hh), or EGFR pathways in non-indicated tumors with relevant genetic abnormalities. Early results from MyPathway merit pre-planned tumor-cohort expansion. Methods: Eligible pts had advanced solid tumors with no curative therapy and molecular alterations in HER2, BRAF, Hh, or EGFR. Pts received standard doses of trastuzumab + pertuzumab (for the HER2 pathway), vemurafenib (BRAF), vismodegib (Hh), or erlotinib (EGFR) based on alteration. The primary endpoint is investigator-evaluated response rate within a tumor-pathway cohort (RECIST 1.1). Cohort size and expansion is determined by Simon’s two-stage design criteria. Results: By December 14, 2015, MyPathway included 129 pts with available baseline assessments and alterations in HER2 (n = 82; 53 amplifications, 23 mutations, 5 both, 1 RBMS-NRG1 fusion), BRAF (n = 33; 18 V600E, 15 other), Hh (n = 8; 7 PTCH1, 1 SMO), or EGFR (n = 6). Pts had a median of 3 (range, 0–10) prior lines of therapy. Best responses (n = 118) are shown below; 11 pts had insufficient follow-up for reevaluation and were not analyzed. 22 pts had PR/CR (1 CR); current response durations were up to 11 months. Conclusions: Targeted therapy produced responses in pts with 9 different tumor types outside of current drug indications. As enrollment increases for all tumor-pathway cohorts, analyses of tumor responses based on specific alterations (eg, HER2 amplifications vs. mutations) are planned. The HER2 amplified colorectal, bladder, and biliary, and the BRAF lung cohorts will be expanded based on observed activity. Clinical trial information: NCT02091141. [Table: see text]

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Targeted therapy for advanced solid tumors based on molecular profiles: Early results from MyPathway, an open-label, phase IIa umbrella basket study.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.15_suppl.lba11511 ◽

2016 ◽

Vol 34 (15_suppl) ◽

pp. LBA11511-LBA11511 ◽

Cited By ~ 4

Author(s):

John D. Hainsworth ◽

Funda Meric-Bernstam ◽

Charles Swanton ◽

Herbert Hurwitz ◽

David R. Spigel ◽

...

Keyword(s):

Targeted Therapy ◽

Solid Tumors ◽

Advanced Solid Tumors ◽

Open Label ◽

Early Results ◽

Open Label Phase ◽

Molecular Profiles

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Interim Analysis on a Dutch HOVON Multicenter Randomized Open Label Phase II Trial on 3 Rituximab Dosing Schemes In Chronic ITP Patients:

Blood ◽

10.1182/blood.v116.21.2514.2514 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2514-2514

Author(s):

Jaap Jan Zwaginga ◽

Ronnie van der Holt ◽

Bart J. Biemond ◽

Peter A.W. te Boekhorst ◽

Mark Levin ◽

...

Keyword(s):

Phase Ii ◽

Conflicts Of Interest ◽

Corticosteroid Treatment ◽

Patient Characteristics ◽

Multicenter Trial ◽

Open Label ◽

Response Data ◽

Best Response ◽

Open Label Phase ◽

Dose Saving

Abstract Abstract 2514 The overall short term effectivity of Rituximab in the treatment of ITP is reported to be around 50%. In most studies the traditional CD20 dosing scheme of 4 weekly interspaced 375 mg/m2 doses is used although other single-arm studies suggest comparable effectivity of lower doses. To investigate alternative dosing schemes, we conducted an open label phase II multicenter trial and randomized 156 ITP patients that were refractory for corticosteroid treatment, between three schemes. Questions were: are higher CD20 peak levels of value and is dose saving a feasible approach in early responding patients? The treatment arms were: A) 375 mg/m2 once a week for 4 weeks, B) 750 mg/m2 once a week for 2 weeks and C) 375 mg/m2 once a week for 2 weeks, in early and sustained responding patients (= within 15 days and still responding at 43 days) and another 2 × 375 mg/m2 to patients not fulfilling these criteria. In retrospect, seven of the 156 patients appeared ineligible at randomization and were therefore excluded from all analyses. Here we report on the best response within 71 days as primary end point for the first 105 patients that were included, i.e. 35 per treatment arm Arm A (n=35) 4 × 375 mg/m2 Arm B (n=35) 2 × 750 mg/m2 Arm C (n=35) 2 or 4 × 375 mg/m2 Patient characteristics Male/female, % 37/63 49/51 43/57 WHO 0/1/2/not reported, % 86/6/–/9. 77/20/3/– 91/9/–/– Age in years, median (range) 56 (19–77) 56 (17–82) 41 (18–80) On stable corticosteroid, % 36 29 46 Splenectomized, % – 15 11 Baseline plt count × 109/l, median (range) 16 (3–31) 15 (1–30) 19 (2–30) Treatment outcome, % Early responses in Arm C 26 All best responses within 71d 46 42 51 CR: >150 × 109 plt/l 20 14 14 GR: >50 × 109 plt/l 20 14 23 MR: >30 × 109 plt/l AND >2 × baseline 6 14 14 No response 54 58 49 Treatment failure at 6 months, % (standard error) 57 (8) 60 (8) 54 (9) So far, on the basis of the within 71 days overall response data, no superior dosing scheme of CD20 can yet be discerned. Disclosures: No relevant conflicts of interest to declare.

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