TTI-622-01: A phase 1a/1b dose-escalation and expansion trial of TTI-622 in patients with advanced hematologic malignancies, including multiple myeloma.
Bibliographic record
Abstract
TPS8071 Background: CD47 is an innate immune checkpoint that binds signal regulatory protein alpha (SIRPα) and delivers a "don’t eat me" signal to suppress macrophage phagocytosis. TTI-622 is a fusion protein consisting of the CD47-binding domain of human SIRPα linked to the Fc region of human IgG4. It is designed to enhance phagocytosis and antitumor activity by preventing CD47 from delivering its inhibitory signal as well as generating a moderate pro-phagocytic signal via IgG4 Fc. CD47 is significantly increased in multiple myeloma (MM) bone marrow mononuclear cells and expression inversely correlates with survival in patients. Relapsed/Refractory (R/R) MM shows particularly high expression of CD47. Preclinical studies demonstrate that the addition of proteasome inhibitors to CD47 blockade significantly increases phagocytosis of MM cells in vitro and anti-myeloma activity in vivo. The ongoing phase 1a part of this study has been previously described. The phase 1b part of the study will determine the safety and efficacy of TTI-622 when given as monotherapy or in combination with selected approved anticancer treatments in patients with hematological malignancies where new treatments with novel mechanism of action are needed. Here we describe 5 RRMM cohorts within phase 1b of the study. Methods: TTI-622-01 is a multi-center Phase 1a/1b study. Phase 1a was designed to determine the MTD, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of QW, Q2W, and Q3W single-agent TTI-622 in R/R lymphoma using a 3+3 dose escalation schema. Phase 1b, ongoing, will determine the safety and recommended dose of TTI-622 to be given as single agent and in combination with carfilzomib + dexamethasone (Kd) in RRMM and will evaluate the preliminary efficacy. Secondary objectives are to further characterize the safety, PK and immunogenicity of TTI-622 when combined with Kd. Patients will be enrolled in 5 separate cohorts: 3 cohorts will explore different doses and administration schedules of TTI-622 combined with the approved dose of Kd; 2 cohorts will explore different doses of TTI-622 monotherapy. Cohorts will be opened in a staggered manner. In each cohort 3 patients will be dosed and followed for 28 days (21 days in the monotherapy) before expanding enrolment to approximately an additional 27 patients. Key eligibility criteria include: relapse or progression following ≥3 prior lines of therapy (including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody), carfilzomib-refractory progressive and measurable disease per IMWG at study entry; age ≥18 years; ECOG performance status ≤2; adequate organ functions; no known CNS involvement; no prior anti-CD47 or anti-SIRPα therapy. Patient recruitment is planned or ongoing at 40 sites worldwide. Clinical trial information: NCT03530683.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".