A randomized phase 2 trial of MM-121, a fully human monoclonal antibody targeting ErbB3, in combination with erlotinib in EGFR wild-type NSCLC patients.
Bibliographic record
Abstract
8051 Background: Heregulin induced activation of ErbB3 has been implicated as a mechanism of resistance to many targeted therapies such as EGFR-TKIs in preclinical models. MM-121 is a monoclonal antibody designed to interfere with this mechanism of resistance. Methods: This Phase 2 trial was a global, multi-center, open-label, parallel cohort study of MM-121 and erlotinib in 3 predefined NSCLC patient groups. Here we report final results from one of the 3 groups: EGFR WT patients. This group comprised 132 patients with WT EGFR who progressed on ≥1 platinum-based SOC therapy and were EGFR TKI-naive. Patients were randomized 2:1 to receive MM-121 20 mg/kg every other week plus daily erlotinib at 100 mg (M) or daily erlotinib alone at 150 mg (E). The primary objective was to compare the progression-free survival (PFS) between M and E. Fresh tissue biopsies were mandatory for evaluation of a pre-specified set of biomarkers mechanistically-linked to ErbB3 signaling. Results: 121 patients (85 (M), 36 (E)) were included in the safety and efficacy analyses. PFS was analyzed after 105 events (73 (M), 32 (E)). Median PFS was 8.1 weeks for arm M and 7.7 weeks for arm E with a HR of 0.898 (95%CI [0.592, 1.363]), log-rank p=0.6129. The objective response rate was 4.7% (95%CI [1.85 - 11.48]) on arm M, and 5.6% (95%CI [1.54 - 18.14]) on arm E. The median overall survival estimate was 27.3 weeks for arm M and 37.3 weeks for arm E, with a HR of 1.499 (95% CI [0.855, 2.629]). The majority of adverse events were reported as mild to moderate in severity and included the following (M vs. E): rash (74% vs. 37%), diarrhea (59% vs. 27%), dermatitis acneiform (28% vs. 11%), dry skin (54% vs. 47%), nausea (29% vs. 14%), fatigue (31% vs. 13%), stomatitis (20% vs. 5%), decreased appetite (37% vs. 16%), weight decreased (27% vs. 11%), and dyspnea (22% vs. 9%). The adverse events were overall manageable and did not impact compliance on treatment. Conclusions: Addition of (M) to (E) was not effective at prolonging PFS in this study population. Overall survival favored the control arm. The observed safety profile is consistent with the expected adverse events associated with ErbB-family inhibitors. Biomarker data will be presented. Clinical trial information: NCT00994123.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 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".