A Phase 1 Study of the Anti-CD37 Antibody-Drug Conjugate AGS67E in Advanced Lymphoid Malignancies. Interim Results
Bibliographic record
Abstract
Abstract Introduction. AGS67E, a fully human IgG2 antibody conjugated to the anti-tubulin agent MMAE through a cleavable linker, targets CD37, a tetraspanin expressed by most B- and T- cell malignancies (Pereira et al, Mol Cancer Ther; 14(7) 2015). Among normal hematopoietic cells, CD37 is expressed mostly on B lymphocytes and to a lesser extent on T lymphocytes, neutrophils, monocytes and a subset of early myeloid precursors. Methods. A phase 1 dose-escalation multicenter study is ongoing to evaluate safety, PK and anticancer activity of AGS67E given as monotherapy once every 3 weeks in patients with relapsed / refractory non-Hodgkin lymphoma without or with growth factor (GF) prophylaxis. Therapy is continued until progression or unacceptable toxicity. Results. Overall 13 patients have been treated in 7 dose cohorts (0.05 to 1.2 mg/kg without GF and 1.2 mg/kg with GF). Diagnoses included: 10 B-cell lymphomas [5 diffuse large B cell lymphomas (DLBCL), 2 follicular lymphomas (FL), 1 mantle cell lymphoma, 1 Waldenström's macroglobulinemia, 1 small lymphocytic lymphoma and 3 T-cell lymphomas (2 mycosis fungoides, 1 peripheral T-cell lymphoma). Median age was 59 (47-85) years. Patients received a median number of 2 (1-10) prior therapies. MTD was exceeded at 1.2 mg/kg given without GF, with all 3 patients treated at this level developing grade 4 neutropenia 8 to 15 days after the first dose. No major non-hematological toxicities have been observed thus far. Table 1.Dose (mg/kg)nmedian n doses (Min-Max)neutropenia in cycle 1other ≥Gr 3 related toxicitiesgr 4gr 4 >7 daysFever0.05111+----0.113---gr3 fall in cycle 30.312----0.613----1.235 (4-5+)311-0.9 enrolling3 (6)2 (1-2)21--1.2 with GF enrolling62 (2-3)----+ = indicates that subjects are continuing to receive treatment Objective responses were observed at the1.2 mg/kg dose level: one patient with DLBCL experienced a CR. The serum AGS67E concentrations indicated non-linear pharmacokinetics at and below 0.6 mg/kg dose levels. At 1.2 mg/kg, the half-life of AGS67E and free MMAE ranged from 1.44-3.08 days and 2.34-3.64 days, respectively. Conclusions: AGS67E administered every three weeks demonstrates a favorable extra-medullary safety profile and signs of anti-lymphoma activity. Expansion cohorts are planned at the Maximum Tolerated Dose both without growth factor and with growth factor. Disclosures Sawas: Seattle Genetics: Research Funding; Gilead Sciences: Honoraria. Savage:Seattle Genetics: Honoraria, Speakers Bureau; BMS: Honoraria; Infinity: Honoraria; Roche: Other: Institutional research funding. Perez:Incyte: Research Funding; Eli Lilly: Research Funding; Dompe: Research Funding; Bristol Meyers Squibb: Research Funding; Agensys: Research Funding; Medimmune: Research Funding; Novartis: Research Funding; Pfizer: Research Funding; Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Research Funding; Immunogen: Research Funding; Tetralogics: Research Funding; PRA: Consultancy. Butturini:Agensys: Employment. Lackey:Agensys, Inc.: Employment. Trave:Agensys: Employment. Anand:Agensys: Employment. Huang:Agensys: Employment. Reyno:Agensys: Employment.
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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 | 0.001 |
| 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 | 0.000 |
| 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".