Promune (agatolimod)

CpG ODN and trastuzumab treatment of metastatic HER2 + breast cancer was safe but was not tolerable for all patients. This combination did induce potentially predictive immune profile changes in treated patients with metastatic HER2 + breast cancer, the significance of which needs to be further explored.

P1, N=36, Completed, City of Hope Medical Center | Active, not recruiting --> Completed

Cancer vaccine ELI-002 2P enhances lymph node delivery and immune response using amphiphile (Amph) modification of G12D and G12R mutant KRAS (mKRAS) peptides (Amph-Peptides-2P) together with CpG oligonucleotide adjuvant (Amph-CpG-7909). ELI-002 2P was safe and induced considerable T cell responses in patients with immunotherapy-recalcitrant KRAS-mutated tumors. ClinicalTrials.gov identifier: NCT04853017 .

ELI-002 2P is a lymph node targeted immunotherapy comprised of Amphiphile (Amph)-modified G12D, G12R, G12V, G12C, G12A, G12S and G13D mutant KRAS peptides together with an Amph-modified CpG oligonucleotide adjuvant...Subsequent patients will receive up to 10 doses of Amph-peptides 7P 700 mcg each (4.9 mg total), together with Amph-CpG-7909 (10.0 mg) administered over a five-month treatment period...An interim analysis is planned using group sequential design for control of overall alpha 0.10. Clinical trial information: NCT05726864.

ELI-002 2P consists of 2 Amph-modified mKRAS peptide antigens, Amph-G12D and Amph-G12R (Amph-Peptides 2P), and a Amph-modified immune-stimulatory oligonucleotide adjuvant (Amph-CpG-7909). This off-the-shelf lymph node-targeted vaccine has many advantages including high immunogenicity yielding balanced CD4+ and CD8+ T cell responses targeting vaccine antigens that are critical for tumor survival. A Phase 1/2 clinical trial investigating a new 7 peptide formulation, ELI-002 7P (G12D, R, V, A, C, S, G13D; NCT NCT05726864), is currently in progress.

In a 3+3 dose escalation, n=22 received a subcutaneous course of 6 prime and 4 booster injections of fixed dose Amph-peptides (1.4 mg), admixed with escalating Amph-CpG-7909 (Table). ELI-002 2P, evaluated in a novel MRD+ trial, was safe with ctDNA and serum tumor biomarker reduction and clearance and notable immune responses. The RP2D is the start dose for a phase 1/randomized phase 2 study evaluating a new seven peptide formulation for G12 D, R, V, S, A, C, and G13D mutated solid tumors (NCT05726864). Clinical trial information: NCT04853017.

P1, N=36, Active, not recruiting, City of Hope Medical Center | Trial completion date: Nov 2022 --> Nov 2023 | Trial primary completion date: Nov 2022 --> Nov 2023

P1, N=36, Active, not recruiting, City of Hope Medical Center | Trial completion date: Nov 2021 --> Nov 2022 | Trial primary completion date: Nov 2021 --> Nov 2022

P1/2, N=1, Terminated, Ludwig Institute for Cancer Research | N=14 --> 1

P1 | "These antigen presenting cells (APC) were matured with CpG7909 and were not genetically modified . SQZ-PBMC-HPV-101 demonstrated clinical feasibility of the Cell Squeeze technology and favorable tolerability of engineered APCs . The study allows for the characterization of the immunogenicity of engineered APCs in humans . Preliminary results warrant the testing in combination with CPI ."

The CpG-B-induced concerted recruitment of cDC1 and CD14 APC to the injection site and its draining lymph nodes may allow for both the (cross-)priming of T cells and their subsequent homing to effector sites.

Here, we describe a unique GPC3-specific aptamer, able to target GPC3-expressing cancer cells in vivo as a means to deliver the immunostimulatory CpG 7909...Final tumor volumes of GRX51-treated animals are consistent with tumor volumes of animals treated with the standard of care compound, sorafenib tosylate...Notably, the combination of GRX51 with pembrolizumab reduced tumor size by 63%. Together, our data show that GRX51 is a novel GPC3-targeting molecule capable of reducing tumor size and priming GPC3-positive tumors for combination immunotherapy, without inducing major systemic toxicity with i.p. injection.