MétaCan
Menu
← Back to cohort

Abstract A074: Maveropepimut-S, a DPX-based immune-educating therapy, combined with Pembrolizumab and Cyclophosphamide in recurrent ovarian cancer, results from the Phase 1/2 PESCO Trial

2024· article· en· W4392376557 on OpenAlexaff
Ana Veneziani, Husam Alqaisi, Douglas G. Millar, Ilaria Colombo, Eduardo González-Ochoa, Swati Atale, Anthony Msan, Judy Quintos, Janelle Ramsahai, Vikas Garg, Pamela Soberanis, Neesha C. Dhani, Robert C. Grant, Lisa Wang, Valerie Bowering, Stéphanie Lheureux, Pamela S. Ohashi, Amit M. Oza

Bibliographic record

VenueCancer Research · 2024
Typearticle
Languageen
FieldMedicine
TopicCancer Immunotherapy and Biomarkers
Canadian institutionsPrincess Margaret Cancer Centre
Fundersnot available
KeywordsPembrolizumabMedicineCyclophosphamideOncologyInternal medicineOvarian cancerCancerGynecologyChemotherapyImmunotherapy

Abstract

fetched live from OpenAlex

Abstract Background: Maveropepimut-S (MVP-S) is a DPX-based immunotherapy that targets survivin-expressing tumor cells and induces a cytotoxic T cell response. Combination with Pembrolizumab (Pemb) and low-dose Cyclophosphamide (CPA) is expected to enhance immune response. This trial aims to evaluate the safety and efficacy of MVP-S, Pemb, and low-dose CPA in patients (pts) with recurrent epithelial ovarian cancer (EOC). Methods: Non-randomized, open-label, phase 1/2 study. Phase 1 escalation cohort used a 3+3 design and included platinum-resistant EOC treated at 2 MVP-S dose levels (DL). All doses were delivered subcutaneously. MVP-S DL1, elected as recommended phase 2 dose (RP2D), included a priming dose of 0.25mL followed by boosters of 0.25mL q6w. MVP-S was combined with CPA (50 mg BID every other week) and Pemb (200 mg q3w). Phase 2 comprised three expansion cohorts. Cohorts A and B allowed high-grade serous (HGSC) or endometrioid tumors sensitive and resistant to platinum, respectively. Exploratory Cohort C enrolled pts with rare EOC subtypes. The primary endpoint was overall response rate (ORR), with secondary endpoints of safety, PFS, and OS. Tumor response was assessed every 6 wks according to RECIST1.1. Activity signal in Cohort A was defined as at least 3/10 partial response (PR) or sustained (>12 wks) stable disease (SD), and for Cohort B as at least 2/10 PR or sustained SD. Biopsies and blood draws were performed before and on treatment for correlative analysis, including flow cytometry, genotyping and ctDNA. The survivin-specific immune response was detected by IFN-γ production after stimulation of PBMCs with survivin peptides. Results:16 pts in the phase 1 escalation cohort (10 DL1 and 6 DL2) and 31 in the phase 2 expansion cohorts (A:11, B:10, C:10) were enrolled. The median age was 60y (range 39-78), and the median prior therapy lines received was 3 (range 1-6). The median follow-up was 14.0 months. Most frequent histologies were HGSC (68%) and clear cell carcinoma (23%). 45 pts were evaluated for safety. The most common AE was injection site reaction, observed in 33 pts (14 G1; 12 G2; 7 G3). Other AEs included fatigue (n=20), anemia (n=18), and nausea (n=16). G1 and G2 accounted for 90% of all related AEs. G3/G4 immune-related AEs occurred in 3 and 1 pts, respectively. Among 44 pts evaluable for efficacy, 1 complete response,9 PR, and 16 SD were observed (ORR 23%). In cohort A, 4/10 pts had PR, and 5/10 had SD (4 of 5 for >12 wks). In cohort B, there was 1/10 PR and 3/10 sustained SD. Cohort C was composed predominantly of clear cell carcinoma, and 2/10 pts had PR, and 2/10 had SD as the best responses. Survivin peptide re-stimulation assays were conducted in 24 pts; survivin-specific immune responses were detected in 14 pts (58%) and correlated with clinical responses (PR/SD) in 13. Conclusion: Combination of MVP-S, low-dose CPA, and Pemb in EOC is well-tolerated and shows promising clinical activity. Primary efficacy endpoints were met in cohorts A and B. Survivin-specific immune responses were correlated with clinical outcomes. Citation Format: Ana C. Veneziani, Husam Alqaisi, Douglas G Millar, Ilaria Colombo, Eduardo Gonzalez-Ochoa, Swati Atale, Anthony Msan, Judy Quintos, Janelle Ramsahai, Vikas Garg, Pamela Soberanis, Neesha C Dhani, Robert C Grant, Lisa Wang, Valerie Bowering, Stephanie Lheureux, Pamela S Ohashi, Amit M Oza. Maveropepimut-S, a DPX-based immune-educating therapy, combined with Pembrolizumab and Cyclophosphamide in recurrent ovarian cancer, results from the Phase 1/2 PESCO Trial [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A074.

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 machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Other · Consensus signal: none
Teacher disagreement score0.006
Threshold uncertainty score0.019

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0000.000
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0060.001

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.

Opus teacher head0.085
GPT teacher head0.423
Teacher spread0.338 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designRandomized trial
Domainnot available
GenreOther

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".

Quick stats

Citations1
Published2024
Admission routes1
Has abstractyes

Explore more

Same venueCancer Research→Same topicCancer Immunotherapy and Biomarkers→French-language works237,207→