carotuximab IV (ENV-105)

"Kairos Pharma Ltd...announces a groundbreaking collaboration with PreCheck Health Services Inc...The partnership focuses on the development of companion biomarkers for Kairos Pharma’s cancer therapy, ENV105, which targets prostate and lung cancers. This strategic agreement aims to advance the precision of patient screening and therapy monitoring for Kairos Pharma’s Phase 1 and Phase 2 clinical trials, with the aim of advancing cancer treatment by identifying patients who will benefit most from ENV105....Kairos Pharma and PreCheck Health Services will utilize advanced molecular diagnostics to corroborate and further develop biomarkers previously identified in a Phase 2 clinical trial. These biomarkers are designed to predict patient responses to ENV105 prior to treatment, offering a more personalized approach to cancer care."

P2, N=100, Recruiting, Edwin Posadas, MD | Trial completion date: Oct 2026 --> Jan 2027 | Trial primary completion date: Oct 2026 --> Jan 2027

P1, N=60, Recruiting, Karen Reckamp, MD, MS | Not yet recruiting --> Recruiting

Our data unveil a tumor-promoting function of ENG in MPNSTs and support the use of this protein as a novel biomarker and a promising therapeutic target for this disease.

Single-agent TRC105 lacks activity in bevacizumab-refractory GBM, possibly secondary to upregulated VEGF-A expression. Meaningful mOS in bevacizumab+TRC105 cohort warrants further trials to investigate efficacy of combination therapy.

P1/2, N=15, Completed, University of Alabama at Birmingham | Active, not recruiting --> Completed

On the functional level, endoglin, both in a ligand dependent and independent manner, did not influence proliferation or migration of the SCC cells. In conclusion, these data show endoglin expression on individual cells in the tumor nests in SCCs and a role for (soluble) endoglin in paracrine signaling, without directly affecting proliferation or migration in an autocrine manner.

Letrozole, everolimus, and carotuximab were tolerated in combination at their single-agent doses. Pharmacokinetic studies revealed an interaction between everolimus and carotuximab.

Inhibitors of the soluble immunosuppressive factors L-kynurenine and prostaglandin E2 efficiently counteract this latter effect. Our data highlight the presence of phenotypically heterogeneous NB-TA-MSC displaying potent immunoregulatory properties towards NK cells, whose inhibition could be mandatory to improve the antitumor efficacy of targeted immunotherapy.

P1, N=60, Recruiting, Karen Reckamp, MD, MS | Not yet recruiting --> Recruiting | Initiation date: Jan 2023 --> Dec 2023

P1, N=60, Not yet recruiting, Karen Reckamp, MD, MS | Trial completion date: Oct 2025 --> Jan 2026 | Initiation date: Aug 2022 --> Jan 2023 | Trial primary completion date: Oct 2024 --> Jan 2025

Quality of life scores were similar for both treatment arms. TRC105 in combination with bevacizumab was well tolerated in patients with recurrent GBM, but no difference in efficacy was observed compared to bevacizumab monotherapy.

P1, N=60, Not yet recruiting, Karen Reckamp, MD, MS

P1/2, N=14, Active, not recruiting, University of Alabama at Birmingham | Trial completion date: Dec 2021 --> Dec 2022 | Trial primary completion date: Dec 2021 --> Dec 2022

Finally, genetic deletion of endoglin from collagen 1a1 expressing cells also did not affect the growth of the mouse KPC tumors. Our results show that although endoglin is highly expressed on PDAC-CAFs and signaling is efficiently inhibited by TRC105, this does not result in decreased tumor growth in the KPC model for pancreatic cancer.

P1/2, N=14, Active, not recruiting, University of Alabama at Birmingham | Trial primary completion date: Aug 2021 --> Dec 2021

P1/2, N=14, Active, not recruiting, University of Alabama at Birmingham | Trial primary completion date: Aug 2020 --> Aug 2021

TRC105 (carotuximab) is an antibody against endoglin, and three of its clinical trials were related to liver diseases. A partial response was achieved when combining TRC105 with sorafenib. Although antiangiogenic therapy still carries some risks, combination therapy with endoglin inhibitors or other targeted therapies holds promise.

The combination of carotuximab with axitinib did not demonstrate additional efficacy over single agent axitinib in patients with mccRCC who progressed following one or more prior VEGF inhibitor treatment.

Taken together these data provide a rationale for combining TRC105 and anti-PD1 therapy and provide additional evidence of endoglin's immunomodulatory role.

P1/2, N=14, Active, not recruiting, University of Alabama at Birmingham | Recruiting --> Active, not recruiting | N=35 --> 14 | Trial completion date: Feb 2021 --> Dec 2021 | Trial primary completion date: Feb 2020 --> Aug 2020