PROCLAIM-CX-072: A Trial to Find Safe and Active Doses of an Investigational Drug CX-072 for Patients With Solid Tumors or Lymphomas

Study Overview
=================
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 trademark of CytomX Therapeutics, Inc.

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

Conditions
-----------------
Solid Tumor, Lymphoma

Intervention / Treatment
-----------------
* Drug: CX-072
* Drug: ipilimumab
* Drug: vemurafenib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed diagnosis of metastatic or advanced unresectable tumors that progressed on standard therapy Agreement to provide mandatory archival tissue or fresh biopsy. At least 18 years of age. Exclusion Criteria: Prior therapy with a chimeric antigen receptor (CAR) T-cell containing regimen. History of severe allergic or anaphylactic reactions to human monoclonal antibody therapy or known hypersensitivity to any Probody therapeutic. 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. 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. History of syndrome or medical condition(s) that requires systemic steroids (> 10 mg daily prednisone equivalents) or immunosuppressive medications. History of allogeneic tissue/solid organ transplant, prior stem cell or bone marrow transplant. Chemotherapy, biochemotherapy, radiation or immunotherapy or any investigational treatment within 30 days prior to receiving any study drug. 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CX-072<br>Monotherapy CX-072 | Drug: CX-072<br> <br> |
| Experimental: CX-072 with Ipilimumab #1<br>Combination CX-072 + ipilimumab (Schedule 1) | Drug: CX-072<br> <br> Drug: ipilimumab<br> <br> |
| Experimental: CX-072 with Ipilimumab #2<br>Combination CX-072 + ipilimumab (Schedule 2) | Drug: CX-072<br> <br> Drug: ipilimumab<br> <br> |
| Experimental: CX-072 with Vemurafenib<br>Combination CX-072 + vemurafenib | Drug: CX-072<br> <br> Drug: vemurafenib<br> <br> |
| Experimental: CX-072 expansion<br>Monotherapy CX-072 | Drug: CX-072<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of subjects experiencing a dose limiting toxicity at various dose levels when given multiple doses of CX-072 as a monotherapy or in combination with ipilimumab or vemurafenib |  | 28 days (dose limiting toxicity period) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of subjects experiencing anti-cancer activity (ORR) at various dose levels when given multiple doses of CX-072 as a monotherapy or in combination with ipilimumab or vemurafenib |  | 2 Years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cancer, checkpoint inhibitor, monotherapy, combination, PD-L1, CTLA-4, solid tumor, lymphoma, BRAF, PROCLAIM, CX-072, PROCLAIM-CX-072