P1152: RESULTS FROM A PHASE I PHARMACOKINETIC (PK) AND SAFETY STUDY OF TRPH-222, A NOVEL CD22-TARGETING ANTIBODY-DRUG CONJUGATE, IN PATIENTS WITH RELAPSED/REFRACTORY B-CELL NON-HODGKIN LYMPHOMA (R/R NHL)
Bibliographic record
Abstract
Background: TRPH-222 is a novel antibody-drug conjugate (ADC) comprised of a humanized anti-CD22 monoclonal antibody and maytansine, a potent microtubule inhibitor, joined by a novel third-generation linker-conjugation technology (SMARTag®). This approach enables site-specific conjugation of the maytansine payload while tightly controlling drug:antibody ratio (DAR), resulting in a highly stable anti-CD22 ADC with a non-cleavable linker designed to widen the therapeutic window. Aims: The primary objectives of this first in human study are to determine the safety, tolerability and pharmacokinetics (PK) of TRPH-222 monotherapy in patients with R/R NHL. Methods: TRPH-222-100 is an open-label, multicenter study comprised of dose-escalation and dose-expansion stages. TRPH-222 was administered IV once every 3 weeks. 22 patients were enrolled in dose-escalating cohorts of TRPH-222 (0.6 mg/kg to 10 mg/kg) from DLBCL, FL, TFL, MCL and MZL histologies, and 10 patients in a dose-expansion cohort (7.5 mg/kg) focusing on DLBCL and FL histologies. Results: As of January 7, 2022, 32 NHL patients have been enrolled: 15 indolent (14 FL and 1 MZL) and 17 aggressive histologies (15 DLBCL, 1 TFL and 1 MCL). Patients had a median age of 64.5 years, a median of 4 prior lines of therapy including 7 patients receiving prior CAR-T treatment. Three DLTs occurred in 2 patients during the study and comprised Grade 3 and 4 transaminase elevations; one each at 4.2 and 10 mg/kg and one Grade 3 thrombocytopenia at 4.2 mg/kg. Treatment-related serious adverse events (AEs) occurred in 2 patients (6.3%), caused by thrombocytopenia and pyrexia (both at 7.5 mg/kg TRPH-222). AEs were more prevalent at doses ≥7.5 mg/kg and less prevalent at lower doses. There was a trend to higher grade AEs in patients with aggressive histologies, compared to indolent ones. The most frequent (≥ 5%) treatment-emergent related AEs (Grade ≥3) included thrombocytopenia (34%), neutropenia (22%), ALT/AST elevation (6%), dry eye (6%) and blurred vision (6%). Cytopenias were non-febrile, infrequent, asymptomatic and resolved without significant intervention. Ocular findings were consistent with known epithelial keratopathy of ADCs and were generally low grade and resolved to ≤ Grade 1 with dose interruptions and/or reductions. Overall, TRPH-222 demonstrated a favourable safety profile with most AEs being predominantly low grade, tolerable, easily managed and reversible. Preliminary efficacy results suggest evidence of anti-tumor activity, most notably in patients with R/R FL. Of the 13 response-evaluable FL patients, 4 complete responses (CR) and 2 partial responses (PR) were observed, with an overall response rate (ORR) of 46% and a complete response rate (CRR) of 31%. Four patients with metabolic CRs maintained these CRs for long periods off treatment; 3 patients remain in CR with responses maintained for up to 25 months. Responses were generally early, durable and CRs were maintained off-therapy. Beyond FL, CRs were also observed in 1 DLBCL patient and in 1 MCL patient. Summary/Conclusion: TRPH-222 was found to be well tolerated at higher dose levels than evaluated for other ADCs. TRPH-222 monotherapy resulted in robust and durable CRs in FL across dose levels where patients were able to discontinue TRPH-222 while remaining in remissions. Collectively, these characteristics of TRPH-222 are favorable for further development in the indolent lymphoma setting either as monotherapy or in combination with other anti-tumor agents in B-cell lymphoma patients.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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) | 0.002 | 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".