Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Results of the TAPPAS trial: An adaptive enrichment Phase 3 trial of TRC105 and pazopanib (P) versus pazopanib alone in patients with advanced angiosarcoma (AS)


30 Sep 2019


Proffered Paper - Sarcoma


Robin Lewis Jones


Annals of Oncology (2019) 30 (suppl_5): v683-v709. 10.1093/annonc/mdz283


R.L. Jones1, V. Ravi2, A.S. Brohl3, S.P. Chawla4, K. GANJOO5, A. Italiano6, S. ATTIA7, M. BURGESS8, K. THORNTON9, L. CRANMER10, L. LIU11, C. Theuer12, R. MAKI13

Author affiliations

  • 1 Medical Oncology, Royal Marsden Hospital NHS Foundation Trust, SW3 6JJ - London/GB
  • 2 Department Of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston/US
  • 3 Department Of Cutaneous Oncology, H. Lee Moffitt Cancer Center, 33612 - Tampa/US
  • 4 Oncology, Sarcoma Oncology Research Center, 90403 - Santa Monica/US
  • 5 Medical Oncology, Stanford University, 94304 - STANFORD/US
  • 6 Early Phase Trials Unit, Institute Bergonié, 33076 - Bordeaux/FR
  • 7 Medical Oncology, MAYO CLINIC IN FLORIDA, 32224 - Jacksonville/US
  • 8 Medical Oncology, University of Pittsburgh Medical Center, 15213 - PITTSBURGH/US
  • 9 Sarcoma, Dana-Farber Cancer Institute, 02115 - BOSTON/US
  • 10 Medicl Oncology, UNIVERSITY OF WASHINGTON, 98109 - SEATTLE/US
  • 11 Clinical Trials Manager, TRACON Pharmaceuticals, 92122 - SAN DIEGO/US
  • 12 Clinical Trials, Tracon Pharmaceuticals, Inc., 92122 - SAN DIEGO/US
  • 13 Medical Oncology, Northwell Health/Cold Spring Harbor Laboratory, 11042 - LONG ISLAND/US



Pazopanib (P) is approved for refractory advanced STS refractory. A retrospective study of 40 AS patients treated with P, reported a median progression-free survival (PFS) of 3.1 months and median overall survival (OS) 9.9 months (Kollar et al, Acta Oncol, 2017). Endoglin is an essential angiogenic receptor expressed on AS cells that is upregulated following VEGF inhibition. TRC105, an endoglin antibody, combined with P produced a median PFS of 7.8 months in chemotherapy-refractory and P-naïve patients enrolled on a phase I-II trial.


TAPPAS was a randomized multicenter trial of TRC105/P vs P that enrolled cutaneous and non-cutaneous AS patients and incorporated an adaptive enrichment design. Key inclusion criteria: 0-2 prior lines of therapy, ECOG ≤ 1. The primary endpoint was PFS by RECIST 1.1 by independent radiographic review (+ cutaneous lesions by photography) (IRR). Secondary endpoints included PFS by investigator review (INV) and OS. An interim analysis to determine the final sample size was conducted following enrollment of 123 patients.


Of 123 pts (TRC105/P, 62; P, 61), 60% were female, 89% were white; median age was 68 years (range: 24-82); 46% were ECOG PS 0; 50% had cutaneous disease; and 28% had no prior treatment. TRC105/P did not prolong median PFS or OS compared to P (Table). Most common all-grade adverse events (AEs) in TRC105/P vs P: fatigue (61% vs 55%); headache (64% vs 23%), diarrhea (57% vs 51%), nausea (48% vs 49%), vomiting (38% vs 23%), anemia (44% vs 9.4%), epistaxis (56% vs 3.8%) & hypertension (36% vs.55%).Table:


Median PFS, mo (95% CI), IRR4.3 (2.9-NE)4.2 (2.8-8.3)
HR (95% CI)0.98 (0.52-1.8)
Median PFS, mo (95% CI), Investigator2.9 (2.6-4.1)3.9 (2.6-5.5)
HR (95% CI)0.77 (0.46-1.78)
Median PFS, cutaneous, mo (95% CI), IRR5.6 (2.6-5.6)4.2 (2.8-8.3)
HR (95% CI)1.07 (0.43, 2.7)
Overall Survival, mo (95% CI)8.7 (7.4, NE)NE (6.8, NE)
Odds ratio (95% CI)0.90 (0.46, 1.74)
Overall Survival, cutaneous, mo (95% CI)8.0 (6.7, NE) NE (6.8, NE)
Odds ratio (95% CI)0.68 (0.25, 1.84)

NE: not estimable; CI: confidence interval; mo: months


TRC105 did not demonstrate activity when combined with P in angiosarcoma. This was the 1st randomized phase III trial in angiosarcoma. These data provide a benchmark of the activity of P in 1st + 2nd-line setting in AS. A number of patients derived durable benefit from the combination schedule, indicating the heterogeneity of angiosarcomas.

Clinical trial identification

NCT 02979899.

Editorial acknowledgement

Legal entity responsible for the study

Tracon Pharmaceuticals, Inc.


Tracon Pharmaceuticals, Inc.


R.L. Jones: Advisory / Consultancy: Tracon; Advisory / Consultancy: Adaptimmune; Advisory / Consultancy: Blueprint; Advisory / Consultancy: Clinigen; Advisory / Consultancy: Deciphera; Advisory / Consultancy: Daichii; Advisory / Consultancy: Eisai; Advisory / Consultancy: Epizyme; Advisory / Consultancy: PharmaMar; Advisory / Consultancy: Lilly; Advisory / Consultancy: Merck. L. Liu: Full / Part-time employment: Tracon. C. Theuer: Full / Part-time employment: Tracon. All other authors have declared no conflicts of interest.

Resources from the same session

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings