Clinical trial NCT03013491: PROCLAIM-CX-072: A Trial to Find Safe and Active Doses of an Investigational Drug CX-072 for Patients With Solid Tumors or Lymphomas
Official title: An Open-Label, Dose-Finding and Proof of Concept Study of the PD-L1 Probody® Therapeutic , CX-072, as Monotherapy and in Combination With Yervoy (Ipilimumab) or With Zelboraf (Vemurafenib) in Subjects With Advanced or Recurrent Solid Tumors or Lymphomas
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Solid Tumor
Lymphoma
Keywords: cancer
checkpoint inhibitor
monotherapy
combination
PD-L1
CTLA-4
solid tumor
lymphoma
BRAF
PROCLAIM
CX-072
PROCLAIM-CX-072
Lead sponsor: CytomX Therapeutics
Sponsor class: INDUSTRY
First posted: 2017-01-06
Enrollment: 196
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this first-in-human study of CX-072 is to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of CX-072 administered intravenously (IV) as a single agent or in combination with ipilimumab or vemurafenib in adult subjects with advanced or recurrent solid tumors or lymphomas. PROCLAIM-CX-072: PRObody CLinical Assessment In Man CX-072 clinical trial

CX-072 is a Probody® therapeutic directed against PD-L1 (programmed cell death ligand 1). Probody therapeutics are proteolytically-activatable antibodies (Abs) designed to widen the therapeutic index by minimizing drug interaction with normal tissue while retaining anti-tumor activity. Probody therapeutics are "masked" to attenuate binding to target in healthy tissue but can become "unmasked" in the tumor microenvironment by tumor-specific protease activity.

PROBODY is a U.S. registered trademark of CytomX Therapeutics, Inc.


Eligibility criteria: Inclusion Criteria:

1. Histologically confirmed diagnosis of metastatic or advanced unresectable tumors that progressed on standard therapy
2. Agreement to provide mandatory archival tissue or fresh biopsy.
3. At least 18 years of age.

Exclusion Criteria:

1. Prior therapy with a chimeric antigen receptor (CAR) T-cell containing regimen.
2. History of severe allergic or anaphylactic reactions to human monoclonal antibody therapy or known hypersensitivity to any Probody therapeutic.
3. Active or history of uveal, mucosal, or ocular melanoma. Human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS)-related illness, chronic hepatitis B or C.
4. History of or current active autoimmune diseases, including but not limited to inflammatory bowel diseases, rheumatoid arthritis, autoimmune thyroiditis, autoimmune hepatitis, systemic sclerosis, systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies, or type 1 insulin dependent diabetes mellitus.
5. History of syndrome or medical condition(s) that requires systemic steroids (\> 10 mg daily prednisone equivalents) or immunosuppressive medications.
6. History of allogeneic tissue/solid organ transplant, prior stem cell or bone marrow transplant.
7. Chemotherapy, biochemotherapy, radiation or immunotherapy or any investigational treatment within 30 days prior to receiving any study drug.
8. Major surgery (requiring general anesthesia) within 3 months or minor surgery (excluding biopsies conducted with local/topical anesthesia) or gamma knife treatment within 14 days (with adequate healing) of administration of any study drug.

Primary outcomes:
measure: The Number of Subjects Experiencing a Dose Limiting Toxicity (DLT) at Various Dose Levels When Given Multiple Doses of CX-072 as a Monotherapy or in Combination With Ipilimumab or Vemurafenib
timeFrame: 28 days (dose limiting toxicity period)
Secondary outcomes:
measure: The Percentage of Subjects Experiencing Anti-cancer Activity (ORR) When Given 10 mg/kg CX-072 as Monotherapy
timeFrame: 2 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: PROCLAIM Investigative Site
state: California
city: Los Angeles
country: United States
facility: PROCLAIM Investigative Site
state: California
city: New Haven
country: United States
facility: PROCLAIM Investigative Site
state: Connecticut
city: Chicago
country: United States
facility: PROCLAIM Investigative Site
state: Illinois
city: Indianapolis
country: United States
facility: PROCLAIM Investigative Site
state: Indiana
city: Boston
country: United States
facility: PROCLAIM Investigative Site
state: Massachusetts
city: Detroit
country: United States
facility: PROCLAIM Investigative Site
state: Michigan
city: New York
country: United States
facility: PROCLAIM Investigative Site
state: New York
city: New York
country: United States
facility: PROCLAIM Investigative Site
state: New York
city: New York
country: United States
facility: PROCLAIM Investigative Site
state: New York
city: Portland
country: United States
facility: PROCLAIM Investigative Site
state: Oregon
city: Nashville
country: United States
facility: PROCLAIM Investigative Site
state: Tennessee
city: Dallas
country: United States
facility: PROCLAIM Investigative Site
state: Texas
city: Houston
country: United States
facility: PROCLAIM Investigative Site
state: Texas
city: Fairfax
country: United States
facility: PROCLAIM Investigative Site
state: Virginia
city: Madison
country: United States
facility: PROCLAIM Investigative Site
state: Wisconsin
city: Amsterdam
country: Netherlands
facility: PROCLAIM Investigative Site
city: Groningen
country: Netherlands
facility: PROCLAIM Investigative Site
city: Rotterdam
country: Netherlands
facility: PROCLAIM Investigative Site
city: Katowice
country: Poland
facility: PROCLAIM Investigative Site
city: Pamplona
country: Spain
facility: PROCLAIM Investigative Site
state: Navarre
city: Barcelona
country: Spain
facility: PROCLAIM Investigative Site
city: Barcelona
country: Spain
facility: PROCLAIM Investigative Site
city: Madrid
country: Spain
facility: PROCLAIM Investigative Site
city: Madrid
country: Spain
facility: PROCLAIM Investigative Site
city: Valencia
country: Spain
facility: PROCLAIM Investigative Ssite
city: Dnepropetrovsk
country: Ukraine
facility: PROCLAIM Investigative Site
city: Glasgow
country: United Kingdom
facility: PROCLAIM Invetigative Site
city: London
country: United Kingdom
facility: PROCLAIM Investigative Site
city: Manchester
country: United Kingdom
facility: PROCLAIM Investigative Site
city: Newcastle upon Tyne
country: United Kingdom
facility: PROCLAIM Investigative Site
Study officials:
affiliation: CytomX Therapeutics
name: Monika Vainorius, M.D.
role: STUDY_DIRECTOR
References:
citation: Naing A, Thistlethwaite F, De Vries EGE, Eskens FALM, Uboha N, Ott PA, LoRusso P, Garcia-Corbacho J, Boni V, Bendell J, Autio KA, Randhawa M, Durm G, Gil-Martin M, Stroh M, Hannah AL, Arkenau HT, Spira A. CX-072 (pacmilimab), a Probody (R) PD-L1 inhibitor, in advanced or recurrent solid tumors (PROCLAIM-CX-072): an open-label dose-finding and first-in-human study. J Immunother Cancer. 2021 Jul;9(7):e002447. doi: 10.1136/jitc-2021-002447.
citation: Sanborn RE, Hamid O, de Vries EG, Ott PA, Garcia-Corbacho J, Boni V, Bendell J, Autio KA, Cho DC, Plummer R, Stroh M, Lu L, Thistlethwaite F. CX-072 (pacmilimab), a Probody PD-L1 inhibitor, in combination with ipilimumab in patients with advanced solid tumors (PROCLAIM-CX-072): a first-in-human, dose-finding study. J Immunother Cancer. 2021 Jul;9(7):e002446. doi: 10.1136/jitc-2021-002446.
citation: Giesen D, Broer LN, Lub-de Hooge MN, Popova I, Howng B, Nguyen M, Vasiljeva O, de Vries EGE, Pool M. Probody Therapeutic Design of 89Zr-CX-072 Promotes Accumulation in PD-L1-Expressing Tumors Compared to Normal Murine Lymphoid Tissue. Clin Cancer Res. 2020 Aug 1;26(15):3999-4009. doi: 10.1158/1078-0432.CCR-19-3137. Epub 2020 Jan 17.