Ongoing, first-in-human, phase I dose escalation study of the investigational CD47-blocker TTI-622 in patients with advanced relapsed or refractory lymphoma.
Bibliographic record
Abstract
3030 Background: CD47 is an immune checkpoint that binds signal regulatory protein alpha (SIRPα) and delivers a "do not eat" signal to suppress macrophage phagocytosis. Cancer cells frequently overexpress CD47 to escape immune surveillance. TTI-622 is a fusion protein consisting of the CD47-binding domain of human SIRPα linked to the Fc region of human IgG4. TTI-622 acts as a decoy receptor, preventing CD47 from delivering its inhibitory signal and enabling macrophage activation and anti-cancer activity via pro-phagocytic signals present on cancer cells. Unlike many CD47-blocking antibodies, TTI-622 does not bind to human erythrocytes and thus may not cause anemia in patients. Methods: In phase 1A, patients with advanced relapsed or refractory lymphoma received IV TTI-622 once per week with dose increased based on traditional 3+3 escalation. Dosing was on a mg/kg basis with the third and subsequent weekly doses approximately 2-fold higher than the first 2 doses (e.g., 0.05, 0.05, and 0.1 mg/kg for weeks 1, 2 and 3). Blood samples were obtained for PK analysis and assessment of CD47 receptor occupancy (RO) on peripheral T cells. Results: At data cut-off, 19 patients (11 M, 8 F) of median age 62 years (range, 24-86) with the following lymphomas: DLBCL 10; HL 6; and TCL, MCL and FL, 1 each, with a median of 3 prior therapies (range, 1-8) were enrolled. No DLTs have been observed in 5 dose levels (0.05 to 4.0 mg/kg). Grade ≥3 related neutropenia occurred in 2 patients; other related AEs occurring in 2 patients each included abdominal pain, fatigue, and nausea; no patients experienced a related SAE. Acute, post-dose platelet decreases occurred transiently and generally were Grade 1- 2; no related Grade ≥3 thrombocytopenia or anemia AEs have been observed. Preliminary PK data indicate a dose-proportional increase in exposure and a T1/2 of approximately 4-5 days following repeat infusions (Week 6). Preliminary biomarker data reveal approximately 60% RO at the end of the first infusion of 2 mg/kg and more sustained 24-hour RO at 1 and 2 mg/kg vs ≤ 0.8 mg/kg. To date, 1 patient with stage 4 non-GCB DLBCL (5 prior therapies) initially achieved PR by Wk 8 and CR by Wk 36, with response ongoing. Conclusions: TTI-622 is well tolerated at doses up to 4 mg/kg per week. Preliminary data indicate dose-dependent increases in PK exposure and target engagement with 1 DLBCL patient having achieved a durable, ongoing CR. Dose escalation is ongoing and additional safety, PK, biomarker and response data will be available at the time of meeting presentation. Clinical trial information: NCT03530683 .
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".