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

e-Poster Display Session

32P - Low immunogenicity and favorable safety seen with novel regimen of tremelimumab (T) plus durvalumab (D) in patients (pts) with unresectable hepatocellular carcinoma (uHCC)

Date

09 Dec 2020

Session

e-Poster Display Session

Presenters

Robin Katie Kelley

Citation

Annals of Oncology (2020) 31 (suppl_7): S1428-S1440. 10.1016/annonc/annonc391

Authors

R.K. Kelley1, A. Negro2, C. Chen3, S. Ali4, N. Standifer3

Author affiliations

  • 1 UCSF - University of California San Francisco - Parnassus Campus, San Francisco/US
  • 2 AstraZeneca USA, Gaithersburg/US
  • 3 AstraZeneca, San Francisco/US
  • 4 AstraZeneca, Cambridge/GB
More

Abstract 32P

Background

In a phase II uHCC study (NCT02519348) the novel regimen T300+D (single, priming dose of T 300 mg + D 1500 mg, then D Q4W) had the best benefit-risk profile vs T or D alone or T75+D (T 75 mg Q4W + D 1500 mg Q4W [4 doses], then D Q4W). Recent data with checkpoint therapies suggest anti-drug antibodies (ADA) can reduce drug efficacy, thus we evaluated immunogenicity and safety in uHCC pts.

Methods

Checkpoint therapy-naïve pts with uHCC who progressed on, were intolerant to, or refused sorafenib were randomized to T300+D, D (1500 mg Q4W), T (750 mg Q4W) or T75+D. Safety and tolerability was the primary endpoint. ADA presence was assessed by electrochemiluminescent bridging assay.

Results

At data cutoff (02/28/2020), 332 pts were enrolled. Treatment-related adverse event (trAE) and ADA incidences are shown in the table. Only 1 pt was ADA+ for D (T75+D arm); ≤ 5 pts in each cohort had treatment-emergent (TE)-ADA to T. Only 1 TE-ADA+ pt had a persistent ADA response ≥16 wks to T. Median max titers to T were 8 (T300+D; T) or 128 (T75+D). The rarity of ADA+ pts barred analysis of associations between positivity and AE type/frequency or efficacy. Table: 32P

T300+D N=74 D N=101 T N=69 T75+D N=82
Median follow up (mo) 12.4 9.4 12.8 10.2
n (%)
Grade 3–4 trAEs 26 (35.1) 20 (19.8) 30 (43.5) 20 (24.4)
Serious trAEs 13 (17.6) 11 (10.9) 17 (24.6) 12 (14.6)
Grade 5 trAEs 2a (2.7) 3b (3.0) 0 1c (1.2)
Discontinuation due to trAEs 8 (10.8) 8 (7.9) 9 (13.0) 5 (6.1)
D ADA evaluable pts (n=154) 55 (74.3) 56 (55.4) 43 (52.4)
ADA+ any visit* 0 0 1 (2.3)
TE-ADA+ 0 0 1 (2.3)
T ADA evaluable pts (n=126) 54 (73.0) 31 (44.9) 41 (50.0)
ADA+ any visit* 7 (13.0) 5 (16.1) 3 (7.3)
TE-ADA+ 4 (7.4) 5 (16.1) 3 (7.3)

apneumonia, death (unknown origin). babnormal hepatic function, hepatic failure, pneumonitis. chepatic failure Pts included from safety analysis set. (all received treatment). *includes pts ADA+ at baseline.

Conclusions

In this study D and T immunogenicity was minimal. ADAs to D or T were few, of short duration (ie, <16 wks) and low titers, suggesting a similarly minimal impact on safety or efficacy. T300+D and D are being evaluated in the phase 3 HIMALAYA study (NCT03298451) in first-line uHCC vs sorafenib.

Clinical trial identification

NCT02519348.

Editorial acknowledgement

Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Lauren D. Van Wassenhove, PhD of Parexel (Hackensack, NJ, USA).

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

R.K. Kelley: Research grant/Funding (institution): Adaptimmune; Advisory/Consultancy, Research grant/Funding (institution): Agios; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): Bristol Myers Squib; Research grant/Funding (institution): EMD Serono; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Merck Sharp & Dohme; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Partner Therapeutics; Research grant/Funding (institution): QED; Research grant/Funding (institution): Taiho; Advisory/Consultancy: IDMC; Advisory/Consultancy: Genentech; Advisory/Consultancy: Roche; Advisory/Consultancy: TargetPharma Solutions; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Gilead. A. Negro: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. C. Chen: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. S. Ali: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. N. Standifer: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. M. Watras: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. B. Evans: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. G.K. Abou-Alfa: Advisory/Consultancy, Research grant/Funding (institution): Agios; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): BeiGene; Advisory/Consultancy: BiolineRx ; Advisory/Consultancy, Research grant/Funding (institution): Bristol Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Celgene; Advisory/Consultancy: CytomX Therapeutics; Advisory/Consultancy: Debiopharm Group; Advisory/Consultancy: Eisai; Advisory/Consultancy, Research grant/Funding (institution): Exelixis; Advisory/Consultancy: Flatiron Health; Advisory/Consultancy: Genoscience Pharma; Advisory/Consultancy: Gilead Sciences; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Janssen ; Advisory/Consultancy: LAM Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy: Loxo; Advisory/Consultancy: Merck Serono.

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
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.