Determination of optimal dose and treatment schedule of the immunotherapeutic vaccine, DPX-Survivac, for combination immunotherapy treatment of ovarian, fallopian tube or peritoneal cancer (OC): A phase Ib study.
Bibliographic record
Abstract
e14577 Background: Survivin is an important protein that regulates apoptosis, proliferation, and angiogenesis of tumors. Increased expression of survivin in various tumors correlates with progression and drug resistance. DPX-Survivac vaccine contains a mix of survivin HLA class I peptides contained in a novel formulation designed to evoke a cytotoxic T cell response against survivin. A phase 1 study (Berinstein et al, Oncoimmunology, 2015) has demonstrated the immunogenicity of DPX-Survivac in combination with metronomic low dose oral cyclophosphamide (mCPA). This study was designed to explore additional dosing schedules that maintain immunogenicity while limiting local injection site reactions in OC. Methods: Stage IIc-IV OC patients with a complete or partial response after first (adjuvant) or second line chemotherapy and with minimal disease were enrolled. Various vaccination schedules as well as boosting without the oil component of DPX-Survivac were tested. Adverse events and dose limiting toxicities were defined by CTCAE v4.03. Vaccine-induced T cell immunity (ELISpot; tetramer analysis) was assessed in purified PBMC. Clinical response was assessed by CT and CA125 using standard RECIST criteria. Results: 36 patients have been treated with different doses and schedules DPX-Survivac vaccination together with mCPA. Several modifications of the dose and schedule resulted in sustained immune responses of varying magnitude and duration. DPX-Survivac was well tolerated. Conclusions: DPX-Survivac in combination with mCPA results in sustained immune responses. This study will allow us to balance the immune response and site of injection profile for different indications including early prevention of recurrence or treatment of small volume active disease. Clinical trial information: NCT01416038.Cohort Pts (n) Priming DPX Boost DPX/Aq Skin ul ceration Grade (n) Immune ELISpot Re sponse 256 to >4000 SFU/ 106 PBMC n (%) Dose (mL) n Freq wks Vol (mL) n Freq wks 1 6 0.25 2 3 0.1 DPX 4 8 2 (2), 3 (1) 6 (100) 2 9 0.25 2 3 0.1 DPX 4 8 3 (1) 4 (44) 3 6 0.25 3 8 N/A 0 0 1 (1) 5 (83) 4 7 0.25 2 6 0.25 DPX 3 6 TBD TBD 5 8 0.25 2 4 0.5 Aq 4 4 TBD TBD
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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) | 0.002 | 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 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".