Phase 1 trial of gavocabtagene autoleucel (gavo-cel, TC-210) in patients (pts) with treatment refractory mesothelioma and other mesothelin-expressing solid tumors.
Bibliographic record
Abstract
8537 Background: We have conducted a Phase 1 trial of gavo-cel, an autologous genetically engineered anti-mesothelin T cell receptor fusion construct (TRuC™) cell therapy in pts with refractory mesothelin-expressing mesothelioma (MPM), ovarian cancer (OvC), cholangiocarcinoma (CHO), or non-small cell lung cancer (NCT03907852). Methods: T cells were engineered with a lentiviral vector to express an anti-mesothelin single domain antibody fused to the CD3ε subunit, which upon translation, integrated into and reprogrammed native T cell receptors to target mesothelin-expressing cancer cells in an HLA-independent manner. Eligibility required central laboratory confirmation of 2+ or 3+ mesothelin expression by IHC in ≥50% of tumor cells. Dose escalation followed a modified 3+3 design. Results: At data cut-off date (January 17th, 2023), 32 pts (23 MPM, 8 OvC, 1 CHO) received a gavo-cel infusion at one of 7 dose levels (DL): DL0 (n = 1, no lymphodepletion [LD]) and DL1 (n = 8), 5x107 transduced cells/m2; DL2 (n = 1, no LD) and DL3 (n = 13), 1x108 transduced cells/m2; DL3.5 (n = 5), 3x108 transduced cells/m2; DL4 (n = 1, no LD) and DL5 (n = 3), 5x108 transduced cells/m2. Median number of prior therapies was 5 (range, 1-13), including immune checkpoint inhibitors (ICI) in 87% of MPM pts. Bridging therapy was required in 24 (75%) pts. Two DLTs were reported: grade (gr) 3 pneumonitis at DL1 and gr5 bronchoalveolar hemorrhage at DL5. At the RP2D (1x108/m2 after LD) 2/13 (15%) pts had reversible gr≥3 CRS. The ORR and disease control rate was 20% and 77%, respectively. The 6-month OS rate was 70.2%. The ORR of pts with MPM or OvC receiving gavo-cel after LD was 21% and 29%, respectively. The median PFS and OS in MPM was 5.6 and 11.1 mos and in OvC was 5.8 and 9.4 mos. Responses correlated with declines in soluble mesothelin related peptides. Peak expansion and persistence correlated with dose and LD administration. At the RP2D, the median Cmax was 14,385 copies/ug gDNA (range, 64.4–100,782) and the median peripheral blood (PB) persistence was 84 days (range: 0-170). Consistent elevation in IL-6 and IFN-γ levels but minimal IL-8 and TNF-α were observed. Gavo-cel expanded preferentially in cancerous tissues, where it was detected long after becoming undetectable in PB. Gavo-cel therapy led to increased CD3+CD8+ T cell tumor infiltration. Non-responders exhibited upregulation of immunoinhibitory ligands (CD155, PDL1), indicating potential resistance mechanisms. Conclusions: A single IV gavo-cel infusion at the RP2D was associated with a manageable toxicity profile and high rates of disease control, including objective responses in pts with refractory MPM and OvC. A phase 2 study is underway testing the safety and efficacy of gavo-cel in combination with checkpoint inhibitors in pts with mesothelin-expressing solid tumors. Clinical trial information: NCT03907852 .
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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 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".