Phase Ib/II open-label, randomized evaluation of efficacy and safety of atezolizumab plus isatuximab versus regorafenib in MORPHEUS-colorectal cancer.
Bibliographic record
Abstract
82 Background: The MORPHEUS platform consists of multiple, global, open-label, randomized Phase Ib/II trials designed to identify early efficacy signals and safety of treatment (tx) combinations across tumor types. Isatuximab (isa; anti-CD38) targets CD38 receptors expressed on immunosuppressive cells in the tumor microenvironment. We hypothesized atezolizumab (atezo; anti–PD-L1) + isa would induce an anti-tumor response beyond that of regorafenib (rego), a multi-kinase inhibitor, in patients (pts) with tx-refractory metastatic colorectal cancer (mCRC). Methods: This randomized Phase Ib/II trial (NCT03555149) enrolled pts with microsatellite stable/mismatched repair proficient mCRC who had received ≤ 2 prior tx lines (fluoropyrimidine-, oxaliplatin- or irinotecan-containing chemotherapy plus a biologic agent). Pts received atezo (1200 mg intravenously [IV] every 3 weeks [q3w]) + isa (10 mg/kg IV q3w) or control tx with rego (160 mg orally days 1–21; dose escalation to 160 mg during Cycle 1 allowed per institutional guidelines). The primary endpoint was objective response rate (ORR; investigator-assessed RECIST 1.1); secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety. Results: Data cutoff date was March 3, 2020. Fifteen pts received atezo + isa and 13 pts received rego. Fourteen atezo + isa pts (93.3%) and 11 control arm pts (84.6%) had received 2 prior lines of tx; 9 atezo + isa pts (60.0%) and 9 control pts (69.2%) had liver metastases at enrollment. No responses were seen in either arm; 3 pts receiving atezo + isa (20.0%) and 8 control pts (61.5%) had stable disease as their best response. DCR (response and/or stable disease ≥ 12 weeks) was 6.7% with atezo + isa and 15.4% with control. One pt treated with atezo + isa beyond progression had prolonged disease stabilization. Median PFS was 1.4 mo (95% CI: 1.4, 1.8) with atezo + isa and 2.8 mo (95% CI: 1.6, 3.1) in the control arm; median OS was 5.1 mo (95% CI: 3.1, 7.8) with atezo + isa and 10.2 mo (95% CI: 4.8, not reached) with control. Tx-related adverse events (AEs, Grade 1-4) occurred in 13 atezo + isa pts (86.7%), and 12 control pts (92.3%). The most common tx-related AEs with atezo + isa were infusion-related reaction (73.3%), nausea (26.7%) and fatigue (20.0%). No Grade 5 AEs occurred in the atezo + isa arm, 1 (7.7%) was reported in the control arm (sepsis, considered unrelated to study tx). No atezo + isa pts and 1 control-arm pt (7.7%) withdrew from treatment due to a tx-related AE. Biomarker analyses did not identify any significant trends related to efficacy. Conclusions: In this trial, superior efficacy of atezo + isa vs rego was not shown. However, the atezo + isa combination was well tolerated, with a manageable safety profile. Clinical trial information: NCT03555149.
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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 | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.008 | 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".