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

• ClinicalTrials.gov Identifier: NCT03013491
• Recruitment Status: Completed
• First Posted: January 6, 2017
• Last Update Posted: February 9, 2022
• Sponsor: CytomX Therapeutics
• Information provided by (Responsible Party): CytomX Therapeutics

Tracking Information

• First Submitted Date: December 26, 2016
• First Posted Date: January 6, 2017
• Last Update Posted Date: February 9, 2022
• Study Start Date: January 2017
• Actual Primary Completion Date: October 6, 2021 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: January 5, 2017): 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 [ Time Frame: 28 days (dose limiting toxicity period) ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: January 5, 2017): 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 [ Time Frame: 2 Years ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Solid Tumor
• Lymphoma

Intervention

• Drug: CX-072
• Drug: ipilimumab
• Drug: vemurafenib

Study Arms

• Experimental: CX-072
  Monotherapy CX-072
  Intervention: Drug: CX-072
• Experimental: CX-072 with Ipilimumab #1
  Combination CX-072 + ipilimumab (Schedule 1)
  Interventions:

  • Drug: CX-072
  • Drug: ipilimumab
• Experimental: CX-072 with Ipilimumab #2
  Combination CX-072 + ipilimumab (Schedule 2)
  Interventions:

  • Drug: CX-072
  • Drug: ipilimumab
• Experimental: CX-072 with Vemurafenib
  Combination CX-072 + vemurafenib
  Interventions:

  • Drug: CX-072
  • Drug: vemurafenib
• Experimental: CX-072 expansion
  Monotherapy CX-072
  Intervention: Drug: CX-072

Publications *

• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Estimated Enrollment (submitted: June 13, 2018): 300
• Original Estimated Enrollment (submitted: January 5, 2017): 150
• Actual Study Completion Date: October 6, 2021
• Actual Primary Completion Date: October 6, 2021 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Netherlands, Poland, Spain, Ukraine, United Kingdom, United States
• Removed Location Countries: Hungary

Administrative Information

• NCT Number: NCT03013491
• Other Study ID Numbers: CTMX-M-072-001
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: CytomX Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: CytomX Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Lawrence Lu, M.D.; CytomX Therapeutics

• PRS Account: CytomX Therapeutics
• Verification Date: February 2022