First-in-human, phase I study of PF-06753512, a vaccine-based immunotherapy regimen (PrCa VBIR), in biochemical relapse (BCR) and metastatic castration-resistant prostate cancer (mCRPC).
Bibliographic record
Abstract
2612 Background: Therapeutic vaccines targeting PC-associated antigens represent attractive approaches in combination with immune checkpoint inhibitors (ICI). Safety/antitumor activity of PF-06753512 (PrCa VBIR) was evaluated in a phase I, dose-escalation and expansion study in patients (pts) with BCR prior to ADT and in pts with mCRPC either prior to or after failure of novel hormone therapy. PrCa VBIR consists of: 1) priming immunization with a replication-deficient adenoviral vector (AdC68) expressing PSA, prostate-specific membrane antigen and prostate stem cell antigen; 2) boosts with plasmid DNA (pDNA) encoding the same antigens by IM electroporation; 3) ICI given subcutaneously, including anti CTLA-4 antibody tremelimumab (TRM) and anti PD-1 antibody sasanlimab (SSL). Methods: AdC68 ± ICI(s) were given on months (mos) 1 and 5 and pDNA ± ICI(s) on mos 2–4 and 6–8. After 8 mos, maintenance pDNA + ICI(s) were given every 1 or 2 mos. In Part A (6 escalation cohorts), pts with mCRPC received AdC68 (4 or 6x10e11 viral particles) + pDNA 5 mg ± ICIs (TRM alone 80 mg; TRM 40 or 80 mg + SSL 130 or 300 mg). In Part B (3 expansion cohorts), pts with mCRPC received AdC68 6x10e11 + pDNA 5 mg + TRM 80 mg + SSL 300 mg; pts with BCR received similar vector and pDNA + TRM 80 mg ± SSL 130 mg. Primary objectives: Assess overall safety (CTCAE v4.03), determine expansion dose. Secondary objectives: Anti-tumor activity (RECIST v1.1, Prostate Cancer Working Group 3, PSA 50 response) and immune response. (Note: Database remains open, some queries pending). Results: As of Sept 15, 2020, 91 pts were treated in dose-escalation (n=38) and expansion (n=53; BCR=35, mCRPC=18). Immune responses (ELISpot) were positive in some pts. Grade (G) 3 or 4 treatment-related adverse events (TRAEs) developed in 38.5% (35/91) of pts. G5 TRAEs occurred in 2 pts (n=1 G4 myasthenia gravis + G5 pulmonary embolism; n=1 G5 myocarditis). irAEs were more frequent in BCR compared to mCRPC. See the table for efficacy data. Conclusions: Vaccination with PrCa VBIR had a manageable safety profile. TRAEs increased when 2 ICIs were given. Some pts with BCR experienced durable PSA-50 responses without ADT; patients with mCRPC had few objective tumor responses, but had prolonged median rPFS. PrCa VBIR appears to stimulate antigen-specific immunity and results in noticeable antitumor activity, particularly in androgen sensitive disease. Clinical trial information: NCT02616185. [Table: see text]
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.004 |
| Insufficient payload (model declined to judge) | 0.004 | 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".