Trillium Therapeutics Provides Update on Its TTI-621 and TTI-622 Clinical Programs
- Category: Antibodies
- Published on Tuesday, 10 April 2018 16:59
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- Successful broad signal-seeking efforts identify T-cell lymphoma as an indication responsive to TTI-621 therapy.
- Focusing TTI-621 intravenous trial on separate cutaneous and peripheral T-cell lymphoma cohorts employing a Simon 2-stage design.
- Deepening the Company’s presence in the CD47 space with a second SIRPaFc decoy receptor, TTI-622.
TORONTO, Canada I April 10, 2018 I Trillium Therapeutics Inc. (Nasdaq:TRIL) (TSX:TRIL), a clinical stage immuno-oncology company developing innovative therapies for the treatment of cancer, today provided the following update on its TTI-621 and TTI-622 clinical programs. TTI-621 and TTI-622 target CD47, a protein commonly found on the surface of cancer cells. CD47 emits a “do not eat” signal to the immune system, allowing cancer cells to evade detection.
TTI-621 (SIRPa-IgG1 Fc) is a decoy receptor that blocks CD47 and delivers an activating signal to effector cells such as macrophages through its IgG1 Fc region. It is being evaluated in two multi-center clinical trials using intravenous or intratumoral administration and preliminary data from both studies were reported at last year’s American Society of Hematology Annual Meeting. Notably, weekly infusions of TTI-621 were shown to be well tolerated and intratumoral injection was observed to reduce local lesions in 9 out of 10 patients with mycosis fungoides, a common type of cutaneous T-cell lymphoma (CTCL). Building upon these monotherapy results, Trillium has refined and focused its TTI-621 clinical program.
“Our thorough signal-seeking efforts in the TTI-621 program have successfully identified T-cell lymphoma as an indication of interest,” said Dr. Niclas Stiernholm, President and CEO of Trillium Therapeutics. “Consequently, we are now moving forward with a more focused TTI-621 program that reflects our commitment to vigorously pursue this signal in both the intravenous and intratumoral trials.”
Recent key modifications to the intravenous dosing study (TTI-621-01, NCT02663518) include:
- Focusing near-term efforts on patients with CTCL and peripheral T-cell lymphoma (PTCL). These patients are being enrolled in separate cohorts that will be evaluated using a Simon 2-stage design, with a maximum of 35 subjects in each cohort.
- Introducing a standardized intra-subject dose intensification schedule for all newly enrolled subjects to increase drug exposure.
- Instituting a number of phase 2-like design elements, such as an independent data monitoring committee and central review of diagnostic pathology as well as radiographic disease imaging.
Recent key changes to the intratumoral dosing study (TTI-621-02, NCT02890368) include:
- Increasing the duration of treatment to allow for weekly continuation therapy.
- Ability to increase the size of each cohort from 12 to 40 patients based on early signs of clinical benefit.
- Establishing new cohorts to study intratumoral TTI-621 in combination with a PD-1 or PD-L1 inhibitor, pegylated interferon-alpha 2a, talimogene laherparepvec (T-vec) or radiation therapy.
TTI-622 (SIRPa-IgG4 Fc) is the second SIRPaFc decoy receptor that Trillium is advancing into the clinic. TTI-622 consists of the same CD47-binding domain of human SIRPa as TTI-621 but linked to an IgG4 Fc region, which has a more restricted ability to engage activating Fc receptors. It is expected to have a different pharmacologic profile than TTI-621 and is being developed primarily for combination therapy. Like TTI-621, TTI-622 has the advantage of minimal binding to human red blood cells, thereby reducing the risk of anemia and a large antigen sink effect.
“TTI-622 allows us to deepen our presence in the CD47 space,” added Dr. Stiernholm. “With this agent we now have two SIRPaFc decoy receptors being evaluated in clinical trials, each with a different level of Fc receptor engagement. We are excited to compare and contrast the activity of these molecules and determine if each has unique applications that could benefit cancer patients.”
A two-part, multicenter, open-label, phase 1a/1b study of TTI-622 in patients with advanced relapsed or refractory lymphoma or multiple myeloma is being initiated, with the first patient expected to be dosed in Q2 2018. In the phase 1a dose-escalation part, patients will be enrolled in sequential dose cohorts to receive TTI-622 once weekly to characterize safety, tolerability, pharmacokinetics, and to determine the maximum tolerated dose. In the phase 1b part, patients will be treated with TTI-622 in combination with rituximab, a PD-1 inhibitor or a proteasome inhibitor-containing regimen.
About Trillium Therapeutics
Trillium Therapeutics Inc. is a clinical stage immuno-oncology company developing innovative therapies for the treatment of cancer. The company’s lead program, TTI-621, is a SIRPaFc fusion protein that consists of the CD47-binding domain of human SIRPa linked to the Fc region of a human immunoglobulin (IgG1). It is designed to act as a soluble decoy receptor, preventing CD47 from delivering its inhibitory (“do not eat”) signal. Neutralization of the inhibitory CD47 signal enables the activation of macrophage anti-tumor effects by pro-phagocytic (“eat”) signals. A Phase 1 clinical trial (NCT02663518) evaluating intravenous dosing of SIRPaFc in patients with advanced cancer is ongoing, and a second Phase 1 trial evaluating direct intratumoral injections is underway in solid tumors and mycosis fungoides (NCT02890368). TTI-621 has recently been granted an Orphan Drug Designation by the FDA for the treatment of cutaneous T-cell lymphoma. TTI-622, an IgG4 SIRPaFc protein which is primarily being developed for combination therapy, is expected to begin clinical testing in 2018. Trillium also has a proprietary medicinal chemistry platform, using unique fluorine chemistry, which permits the creation of new chemical entities from validated drugs and drug candidates with improved pharmacological properties. Stemming from this platform, the company’s most advanced preclinical program is an orally-available epidermal growth factor receptor antagonist with increased uptake and retention in the brain. In addition, a number of compounds directed at undisclosed immuno-oncology targets are currently in the discovery phase.
SOURCE: Trillium Therapeutics