Updated results from the trastuzumab deruxtecan (T-DXd) 5.4 mg/kg triplet combination of DESTINY-Gastric03 (DG-03): First-line (1L) T-DXd with fluoropyrimidine (FP) and pembrolizumab in advanced/metastatic HER2-positive (HER2+) esophageal adenocarcinoma, gastric cancer (GC), or gastroesophageal junction adenocarcinoma (GEJA).
Bibliographic record
Abstract
448 Background: T-DXd is a HER2-directed antibody-drug conjugate; T-DXd 6.4 mg/kg monotherapy is approved for patients with metastatic HER2+ GC/GEJA who have received a prior trastuzumab-based regimen. Preliminary results from DG-03 Part 2 showed feasibility and promising antitumor activity with 1L T-DXd 6.4 mg/kg (arm D) or 5.4 mg/kg (arm F) with FP and pembrolizumab in patients with esophageal adenocarcinoma/GC/GEJA. T-DXd 6.4 mg/kg and FP with pembrolizumab was associated with higher than expected toxicity; alternatively, early safety data from T-DXd 5.4 mg/kg triplet combination showed a manageable safety profile. We report updated results for arm F from DG-03 Part 2 with an approximate time-matched analysis with arm D. Methods: DG-03 (NCT04379596) is a Phase 1b/2 multicenter, open-label, dose-escalation (Part 1) and -expansion (Parts 2, 3, and 4) study. In Part 2, patients with HER2+ (immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization–positive by local testing) esophageal adenocarcinoma/GC/GEJA, irrespective of programmed cell death ligand 1 status, and no prior treatment for metastatic disease were enrolled. In arm D, patients received T-DXd 6.4 mg/kg intravenous (IV) infusion every 3 weeks (Q3W) and FP (5-fluorouracil [5-FU] 600 mg/m 2 continuous IV or capecitabine [cape] 1000 mg/m 2 twice daily [BID]) with pembrolizumab 200 mg IV Q3W; in arm F, patients received T-DXd 5.4 mg/kg IV Q3W and FP (5-FU 600 mg/m 2 continuous IV or cape 750 mg/m 2 BID) with pembrolizumab 200 mg IV Q3W.Primary endpoint was confirmed objective response rate by investigator assessment (INV) per RECIST 1.1. Secondary endpoints included duration of response by INV and progression-free survival by INV. Safety and tolerability were also assessed. Results: A time matched analysis was performed to compare the efficacy of arm D (n=43), data cut-off (DCO) October 27, 2022, and arm F (n=32), DCO May 6, 2024, given the limited follow up of the 5.4mg/kg. The median duration of follow up for the two cohorts was 4.1 months and 4.6 months for arm D and arm F, respectively. Objective response rate for arm D was 41.9% and 59.4% for arm F. Median PFS was 6.4 months (95% CI: 5.0, NC) for arm D and 5.8 months (95% CI: 5.6, NE) for arm F. At DCO, the median overall survival in both arms was not reached. Updated time matched safety and efficacy data will be provided at the time of presentation. Conclusion: The time matched analysis shows that lowering the dose of T-DXd to 5.4 mg/kg from 6.4 mg/kg and lowering the starting dose of capecitabine, did not result in decrease in efficacy of the combination of T-DXd + FP + pembrolizumab. Funding: This study is sponsored by AstraZeneca in collaboration with Daiichi Sankyo. In March 2019, AstraZeneca entered into a global development and commercialization collaboration agreement with Daiichi Sankyo for trastuzumab deruxtecan (T-DXd; DS-8201). Editorial acknowledgment: Under guidance of the authors and in accordance with Good Publication Practice, medical writing and editorial support was provided by Carmen Grimaldos, PhD, of Helios Medical Communications, part of Helios Global Group, and was funded by AstraZeneca. Clinical trial information: NCT04379596 .
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 | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| 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".