Glofitamab monotherapy in pts with relapsed/refractory (R/R) large B-cell lymphoma (LBCL): Extended follow-up and landmark analyses from a pivotal phase II study.
Bibliographic record
Abstract
7550 Background: Glofitamab is a CD3xCD20 bispecific antibody delivered in a fixed course of 12 three-weekly cycles. In a Phase II study (NCT03075696), glofitamab induced high complete response (CR) rates and had manageable toxicity in pts with R/R LBCL (Dickinson et al. 2022). We present an extended follow-up and a landmark analysis to assess the outcomes of pts in CR. Methods: Pts with LBCL and ≥2 prior therapies received 1000mg obinutuzumab pretreatment 7 days prior to the first glofitamab dose. IV glofitamab was given as step-up doses: 2.5mg on Day (D) 1 of Cycle (C) 1, 10mg on C1D8 and 30mg (target dose) on D1 of C2–12 (21-day cycles). The primary endpoint was independent review committee (IRC)-assessed CR rate. PFS and OS post-hoc analyses were performed in responders (landmark for CR at C3 or end of treatment [EOT]). Results: As of Oct 10, 2022, 154 pts had received ≥1 dose of study treatment; baseline characteristics were as previously presented. Median number of prior therapies was 3 (range: 2–7); 33% had received prior CAR T-cells and 85% were refractory to their most recent regimen. Median time on study was 20.1 months (range: 0–32). The investigator (INV)-assessed CR rate (BOR) was 38% (40% by IRC) and overall response rate was 59% (52% by IRC). CR rates were consistent in pts with and without prior CAR-Ts (37% vs 39%). After a median follow-up of 18.3 months (range: 0–30) in pts with a CR (BOR), most CRs (39/59; 66%) were ongoing. Median duration of CR (DoCR) was 24.1 months (95% CI: 19.8–NE); an estimated 70% of pts with a CR at any time remained in remission at 18 months. The 18-month OS rate was 41% (95% CI: 32.1–49.3). Landmark analyses at 1 year in pts with a CR pre-C3 (PFS rate: 71%, OS rate: 92%) and in pts with a CR at EOT (PFS rate: 80%, OS rate: 94%) showed that most pts were progression free and alive. In a cohort of 101 pts treated with glofitamab doses below the recommended Phase II dose but ≥10mg with longer median CR follow-up (31 months, range: 1–49), the median DoCR was 30.1 months (95% CI: 5.5–NE) and 55% of pts were still in remission at data cut-off. This further confirms the highly durable responses achieved with glofitamab. CRS (by ASTCT) remained the most common adverse event (AE), occurring in 64% of pts, and was mostly Grade (Gr) 1 (48%) or Gr 2 (12%); Gr 3 (3%) and Gr 4 (1%) events were uncommon. The incidence of AEs and serious AEs was stable compared with earlier analyses, with one new Gr 3 AE (acute kidney injury), one new Gr 2 neurologic AE (agitation) and no new glofitamab-related Gr 5 AEs reported. Conclusions: Glofitamab continued to demonstrate durable responses, with most pts in CR at EOT still in remission without new AEs. These data support the potential for favorable long-term outcomes with fixed-duration glofitamab for R/R LBCL. Updated analyses, including a larger population with a median CR follow up of approximately 20 months post-EOT, will be presented. Clinical trial information: NCT03075696 .
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.005 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.001 | 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".