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 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 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".