Analysis of rational combination immunotherapy strategies in prostate cancer: scientific premise and disease stage.
| NCT number | Phase | Description | Combination rationale & scientific premise | Disease stage |
|---|---|---|---|---|
| NCT03532217 | I | Neoantigen DNA vaccine in combination with nivolumab/ipilimumab and PROSTVAC in hormone-sensitive mCRPC | “Prime, expand, sustain”: Neoantigen & PROSTVAC vaccines prime diverse T-cell clones; dual checkpoint blockade (Ipi/Nivo) expands and sustains their activity, creating a powerful, multi-pronged immune attack. | Metastatic (mCRPC) |
| NCT02649855 | II | Docetaxel and PROSTVAC for mCRPC | Sequential modality: Tests if chemotherapy-induced immunogenic cell death provides an antigen source to enhance the efficacy of a subsequent vaccine, or if concurrent administration is feasible and synergistic. | Metastatic (mCRPC) |
| NCT02325557 | I/II | ADXS31-142 alone and in combination with PD-1/PD-L1 inhibitors | Innate + adaptive activation: Attenuated Listeria induces potent innate immunity and delivers tumor antigens (e.g., PSA). Checkpoint inhibitors prevent exhaustion of the activated T-cells, aiming to convert a strong immune response into a clinical benefit. | Metastatic (mCRPC) |
| NCT04382898 | I/II | PRO-MERIT in mCRPC | mRNA precision + checkpoint blockade: An mRNA vaccine encoding multiple prostate-associated antigens (PAP, PSA, PSMA, etc.) precisely directs the immune response. Combined with PD-1 blockade to overcome the adaptive resistance that often follows vaccination. | Metastatic (mCRPC) |
| NCT04989946 | I/II | ADT, +/– pTVG-AR, and +/– nivolumab in newly diagnosed, high-risk prostate cancer | Early intervention & AR targeting: Tests a “chemo-free” immuno-hormonal combination in high-risk localized disease. ADT remodels the TME; an AR-targeting vaccine primes anti-tumor immunity; and nivolumab prevents T-cell exhaustion, aiming for curative-intent synergy. | High-risk localized |
| NCT04090528 | II | PIVG-HP DNA vaccine, +/– pTVG-AR DNA vaccine, and pembrolizumab in mCRPC | Dual-antigen vaccination + checkpoint blockade: Combines vaccination against two key prostate antigens (PAP and AR) to broaden immune targeting, supported by PD-1 inhibition to maintain the functionality of the activated T-cell pools. | Metastatic (mCRPC) |
| NCT03600350 | II | pTVG-HP and nivolumab in non-metastatic PSA-recurrent prostate cancer | Early biochemical recurrence: Intervenes at a minimal disease state where the immune system is likely more competent. Aims to delay metastatic progression by inducing anti-PAP immunity and blocking its eventual exhaustion. | Non-metastatic (BCR) |
| NCT03315871 | II | Combination immunotherapy in biochemically recurrent prostate cancer (CRPC) | Platform for early intervention: A biomarker-driven umbrella study testing various immunotherapies in BCR, recognizing this as a critical window to eradicate micrometastatic disease before the TME becomes overwhelmingly immunosuppressive. | Non-metastatic (BCR) |
NCT: National Clinical Trial; ADT: androgen deprivation therapy; AR: androgen receptor; BCR: biochemical recurrence; mCRPC: metastatic castration-resistant prostate cancer; PAP: prostatic acid phosphatase; PSA: prostate-specific antigen; TME: tumor microenvironment. Adapted from https://clinicaltrials.gov/ and Meng et al [6] (CC-BY).
DKN: Conceptualization, Writing—original draft, Writing—review & editing, Software, Methodology. VB: Investigation, Software. IJK: Visualization, Investigation. XZ: Supervision, Validation, Writing—review & editing. All authors read and approved the submitted version.
The authors declare that they have no conflicts of interest.
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