NCT01103635

A Phase 1 Dose-Escalation Trial To Evaluate Safety, Tolerability And Immune Pharmacodynamics Of Combined Administration Of Tremelimumab (Blocking Anti-CTLA-4 Antibody) And CP-870,893 (Agonist Anti-CD40 Antibody) In Patients With Metastatic Melanoma

Completed Phase 1 Last updated 6 April 2020

What this trial tests

Phase 1 trial testing CD40 agonist monoclonal antibody CP-870,893 in Recurrent Melanoma in 25 participants. Completed in 2 May 2016.

Timeline

1 February 2010

Primary endpoint
1 May 2016

2 May 2016

Quick facts

Lead sponsor	Abramson Cancer Center at Penn Medicine
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	25
Start date	1 February 2010
Primary completion	1 May 2016
Estimated completion	2 May 2016
Sites	1 location across United States

Drugs / interventions tested

• CD40 agonist monoclonal antibody CP-870,893 — full drug profile →
• tremelimumab (TREMELIMUMAB) — full drug profile →
• laboratory biomarker analysis — full drug profile →

Conditions studied

• Recurrent Melanoma — all drugs for Recurrent Melanoma →
• Stage IV Melanoma — all drugs for Stage IV Melanoma →

Sponsor

Abramson Cancer Center at Penn Medicine — full company profile →

Who can join

18 and older, any sex, with Recurrent Melanoma or Stage IV Melanoma. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Toxicity as assessed by CTCAE v3.0
  Time frame: 2 years
  Toxicities which occur during later cycles will be monitored and described separately. The MTD is defined as the dose level at which 0-1/6 patients experience DLT in the first 12 week cycle and at least 2/3 or 2/6 patients treated at the next higher dose level (unless MTD is level 4) experience DLT in the first 12 week cycle.
• Response
  Time frame: 2 years
  Clinical response will be scored using RECIST criteria. Patients who do not complete a clinical response evaluation will be scored as unevaluable. The objective response rate is defined as the proportion of patients treated at the MTD who achieve either a complete or partial response. Unevaluable patients are included in the calculation of the objective response rate.
• Immunological outcomes (analysis of antigen presenting cell activation, antigen-specific T cells, and tumor-specific T cells)
  Time frame: 2 years
  Analysis of antigen presenting cell (APC) activation, 2) analysis of antigen-specific T cells and 3) tumor-specific T cells, as described in Section 7.2. For T cell response analyses, overall immune response is defined as \>2 fold pre-treatment/post-treatment increase in any of the key T cell parameters.

Sponsor's own description

RATIONALE: Monoclonal antibodies, such as tremelimumab and CD40 agonist monoclonal antibody CP-870,893, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry cancer-killing substances to them. Giving tremelimumab together with CD 40 agonist monoclonal antibody CP-870, 893 may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of giving tremelimumab together with CD40 agonist monoclonal antibody CP-870,893 in treating patients with metastatic melanoma.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Inflammation and tumor progression: signaling pathways and targeted intervention.
   Zhao H, Wu L, Yan G, Chen Y, et al · · 2021 · cited 1932× · PMID 34248142 · DOI 10.1038/s41392-021-00658-5
2. Macrophages and therapeutic resistance in cancer.
   Ruffell B, Coussens LM. · · 2015 · cited 1235× · PMID 25858805 · DOI 10.1016/j.ccell.2015.02.015
3. Targeting tumor-associated macrophages to synergize tumor immunotherapy.
   Xiang X, Wang J, Lu D, Xu X. · · 2021 · cited 712× · PMID 33619259 · DOI 10.1038/s41392-021-00484-9
4. Progress in tumor-associated macrophage (TAM)-targeted therapeutics.
   Ngambenjawong C, Gustafson HH, Pun SH. · · 2017 · cited 659× · PMID 28449873 · DOI 10.1016/j.addr.2017.04.010
5. Tumor-associated macrophages: from basic research to clinical application.
   Yang L, Zhang Y. · · 2017 · cited 654× · PMID 28241846 · DOI 10.1186/s13045-017-0430-2
6. Next generation of immune checkpoint therapy in cancer: new developments and challenges.
   Marin-Acevedo JA, Dholaria B, Soyano AE, Knutson KL, et al · · 2018 · cited 582× · PMID 29544515 · DOI 10.1186/s13045-018-0582-8
7. New horizons in tumor microenvironment biology: challenges and opportunities.
   Chen F, Zhuang X, Lin L, Yu P, et al · · 2015 · cited 521× · PMID 25857315 · DOI 10.1186/s12916-015-0278-7
8. Targeting macrophages in cancer immunotherapy.
   Duan Z, Luo Y. · · 2021 · cited 462× · PMID 33767177 · DOI 10.1038/s41392-021-00506-6