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 display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care

2945 - Preliminary results of the first-in-human, dose-finding PROCLAIM-CX-072 trial evaluating the PD-L1 Probody therapeutic CX-072 in combination with ipilimumab (ipi) in patients (pts) with advanced solid tumors

Date

22 Oct 2018

Session

Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care

Topics

Clinical Research

Tumour Site

Presenters

Ruth Plummer

Citation

Annals of Oncology (2018) 29 (suppl_8): viii133-viii148. 10.1093/annonc/mdy279

Authors

R. Plummer1, R.E. Sanborn2, E.G..E. de Vries3, P. Lorusso4, H. Arkenau5, N. Uboha6, J. Wydmanski7, M.J. Fidler8, V. Boni9, J. Garcia-Corbacho10, R. Humphrey11, M. Will11, K.A. Autio12, A.B. El-Khoueiry13, C.W. Menke-van der Houven van Oordt14, F. Thistlethwaite15

Author affiliations

  • 1 Northern Institute For Cancer Research, Newcastle University, NE2 4HH - Newcastle upon Tyne/GB
  • 2 Earle A. Chiles Research Institute, Providence Cancer Institute, Portland/US
  • 3 Medical Oncology, Universitair Medisch Centrum Groningen, 9700 RB - Groningen/NL
  • 4 Yale Cancer Center, Yale University School of Medicine, New Haven/US
  • 5 Scri, Sarah Cannon Research Institute SCRI UK, W1G 6AD - London/GB
  • 6 Carbone Cancer Center, University of Wisconsin, Madison/US
  • 7 Vegamed, NZOZ, Katowice/PL
  • 8 Medical Oncology, Rush University Medical Center, Chicago/US
  • 9 Medical Oncology, START Madrid-CIOCC HM Hospital Sanchinarro, Madrid/ES
  • 10 Medical Oncology, Hospital Clinic Barcelona, Barcelona/ES
  • 11 Medical Oncology, CytomX Therapeutics, South San Francisco/US
  • 12 Medical Oncology, Memorial Sloan Kettering Cancer Center, New York/US
  • 13 Medical Oncology, USC/Norris Comprehensive Cancer Center, Los Angeles/US
  • 14 Medical Oncology, VUMC Cancer Centre Amsterdam, Amsterdam/NL
  • 15 Medical Oncology, The Christie NHS Foundation Trust and University of Manchester, M20 4BX - Manchester/GB
More

Resources

Abstract 2945

Background

Combination treatment with PD-1 + CTLA-4 checkpoint inhibitors shows improvement in breadth, depth, and durability of response, coupled with a disproportionate increase in immune-related adverse events (irAE). CX-072, a Probody™ therapeutic (Pb-Tx) directed against PD-L1, is designed to be preferentially activated by tumor-associated proteases and not in healthy tissue. Preclinically, anti–PD-1 Pb-Tx + anti–CTLA-4 showed comparable efficacy with improved safety compared to the non–Pb-Tx combination control. This dose-escalation cohort examines safety and tolerability of CX-072 (anti-PD-L1 Pb-Tx) + the CTLA-4 inhibitor ipi in pts with advanced solid tumors.

Methods

In this ongoing phase 1/2 study (NCT03013491), PD-1, PD-L1, and CTLA-4 inhibitor-naive pts receive combination CX-072 + ipi (part B1). Planned doses of CX-072 (0.3, 1, 3, or 10 mg/kg) are administered in combination with ipi (3, 6, or 10 mg/kg) every 21 days for 4 cycles, followed by CX-072 monotherapy every 14 days.

Results

As of April 20, 2018, part B1 enrolled 16 pts. Median age (range) and number of prior anticancer treatments was 60 years (28-70) and 3 (1-12), respectively. 6 pts were still on treatment at time of data cut. Median number (range) of CX-072 (0.3, 1, 3, or 10 mg/kg) and ipi (3 mg/kg) doses were 3 (1-20) and 3 (1-4), respectively. All cohorts through 10 mg/kg CX-072 (dose selected for monotherapy cohort expansion) are now enrolled without reaching the MTD. 1 DLT (grade 3 dyspnea, 0.3 mg/kg CX-072 + ipi) occurred. Grade 3 treatment-related (TR) irAEs occurred in 2 pts (12.5%; colitis and dyspnea/pneumonitis). No subject discontinued due to TR irAEs. Best response in 10 evaluable pts included 1 complete response (anal SCC, 0.3 mg/kg CX-072 + ipi), 2 partial response (non-seminoma testicular, 1 mg/kg CX-072 + ipi; small bowel, 3 mg/kg CX-072 + ipi), 1 stable disease, and 6 progressive disease.

Conclusions

Despite small pt numbers and limited follow up, early data suggest manageable safety profiles at all doses and antitumor activity with CX-072 + ipi in tumor types not approved for checkpoint inhibitors. The study is ongoing and escalation of ipi to 10 mg/kg is pending.

Clinical trial identification

NCT03013491.

Legal entity responsible for the study

CytomX Therapeutics, Inc.

Funding

CytomX Therapeutics, Inc.

Editorial Acknowledgement

Editorial support was provided by Andrew Occiano (ApotheCom, San Francisco, CA).

Disclosure

R.E. Sanborn: Research funding/grant: Merck; Investigator initiated Study: BMS, Medimmune; Institutional research support, honoraria: AstraZeneca; Advisory board: AstraZeneca, Seattle Genetics, Takeda, Genentech, Abbvie, Celldex; Travel, accommodations, investigator meeting: Janssen. E.G.E. de Vries: Research grant: Amgen, Genentech, Roche, Chugai, Synthon, CytomX, Nordic Nanovector, Regeneron, G1 Therapeutics, AstraZeneca, Radius Health (institution); Consulting: Pfizer, Sanofi (institution). P. Lorusso: Data safety monitoring board: Agios, FivePrime, Halozyme; Advisory board: Alexion, Ariad, CytomX, GenMab, Genentech, Glenmark, Ignyta, Menarini, Novartis, Omniox, Takeda, imCORE Alliance, Roche-Genentech. N. Uboha: Consulting: EMD Serono, Lilly, FlatIron, GLG. M.J. Fidler: Consulting: Genentech, AstraZeneca, Takeda, AbbVie; Speakers bureau: Merck, Celgene, Genentech, AbbVie. R. Humphrey, M. Will: Employment: CytomX Therapeutics. K.A. Autio: Research funding: CytomX, Pfizer, Lilly, GSK, Merck, ARMO Biosciences. F. Thistlethwaite: Research grant: Novartis; Consulting: Pfizer, BMS, Octimet, Achilles Therapeutics, Evelo Biosciences; Honorarium: Novartis; Speakers' bureau: BMS. 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.