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

Poster Discussion – Genitourinary tumours, non-prostate

3113 - APACHE: an open label, randomized, phase 2 study of Durvalumab (Durva), alone or in combination with Tremelimumab (Treme), in patients (pts) with refractory germ cell tumors (GCT): results from the expanded combination therapy cohort

Date

29 Sep 2019

Session

Poster Discussion – Genitourinary tumours, non-prostate

Presenters

Elena Farè

Citation

Annals of Oncology (2019) 30 (suppl_5): v356-v402. 10.1093/annonc/mdz249

Authors

E. Farè1, D. Raggi2, P. Giannatempo1, M. Colecchia3, G. Calareso4, S.M. Ali5, J. Chung5, J.S. Ross6, A. Necchi1

Author affiliations

  • 1 Medical Oncology, Istituto Nazionale dei Tumori di Milano - Fondazione IRCCS, 20133 - Milan/IT
  • 2 Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 3 Pathology, Istituto Nazionale dei Tumori di Milano - Fondazione IRCCS, 20133 - Milan/IT
  • 4 Radiology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 5 Clinical Development, Foundation Medicine, 02141 - Cambridge/US
  • 6 Pathology, Foundation Medicine, 02141 - Cambridge/US

Resources

Login to access the resources on OncologyPRO.

If you do not have an ESMO account, please create one for free.

Abstract 3113

Background

Interim results from APACHE (NCT03081923) have been presented, with the monotherapy arm stopped for futility (Necchi, Eur Urol 2018). Updated results with the expanded combination therapy cohort are presented.

Methods

Apache is an open-label, randomized, 3-stage, phase 2 study. Pts who have failed ≥2 chemotherapy (CT) regimens received Durva, 1.5 gr q4w, x 13 cycles (arm A) or Durva plus with Treme, 75 mg q4w, x 4 cycles, followed by Durva alone x total 13 cycles (arm B). The primary endpoint is the modified objective response-rate (mORR=RECIST 1.1 complete or partial response [PR] or stable disease [SD]+STM reduction >10%). H0: mORR rate ≤10%, H1: mORR ≥25% (α and β = 10%). The total sample size of 120 pts is split into 3 stages: in stage 1, each arm is terminated whenever no response is observed in 11 pts/arm. In stage 2, 29 additional pts/arm are enrolled. Biomarker analyses include: PD-L1 expression on immune cells (Ventana SP142) and comprehensive genomic profiling (CGP) with FoundationOne assay.

Results

From 02/17-11/18, 29 pts were enrolled (11 arm A and 18 arm B). 22 had gonadal and 7 extragonadal GCT, 19 had received >/=3 prior CT regimens. Median tumour mutational burden (TMB) was 4 mutations (mut)/mb, 1 pt showed microsatellite instability in arm A. 10 pts (34.5%) experienced any-Grade AEs, without differences between arms. In the expanded arm B, 2 responses (11.1%, 1 RECIST-PR in seminoma and 1 SD with STM reduction in nonseminoma) and 2 SD were observed. PD occurred regardless of PD-L1 expression and TMB. After median follow-up of 16.3 months, 12-month OS in arm A was 30% (95%CI: 7.2-57.7) and in arm B was 29.6% (95%CI: 10.2-52.2). Further CT post-PD was administered in 8 pts (27.6%), but was mostly ineffective (7/8 SD/PD).

Conclusions

Despite objective responses were rare with IO, long-term OS results are encouraging in very highly pre-treated GCT pts, suggesting a role for maintenance approach in earlier setting (2nd-line CT), and privileging Durva+Treme due to more responses. Conventional IO biomarkers did not allow for patient selection, and further research is warranted.

Clinical trial identification

NCT03081923.

Editorial acknowledgement

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

S.M. Ali: Full / Part-time employment: Foundation Medicine. J. Chung: Full / Part-time employment: Foundation Medicine. J.S. Ross: Full / Part-time employment: Foundation Medicine. A. Necchi: Honoraria (institution), Advisory / Consultancy: Merck; Honoraria (institution), Advisory / Consultancy: AstraZeneca; Honoraria (institution), Advisory / Consultancy, Spouse / Financial dependant: Bayer; Advisory / Consultancy: BMS; Advisory / Consultancy: Clovis; Honoraria (institution), Advisory / Consultancy: Janssen; Honoraria (institution), Advisory / Consultancy: Roche. All other authors have declared no conflicts of interest.

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.