Immune Checkpoint Inhibitor Rechallenge in Renal Cell Carcinoma: Current Evidence and Future Directions
Abstract
:Simple Summary
Abstract
1. Introduction
2. Biological Rationale of Resistance to Immunotherapy
2.1. Intrinsic Tumor Features
2.2. Tumor Microenvironment
3. Literature Search and Selection of Trials
4. ICI Rechallenge in RCC: Current Evidence of Therapeutic Strategies for Overcoming Resistance
4.1. Combination of ICIs
4.1.1. Retrospective Data
4.1.2. Data from Prospective Trials
4.2. Combination of Antiangiogenics Drugs and ICIs
Data from Prospective Trials
5. Ongoing Trials of ICI Rechallenge in RCC
5.1. SNAPI
5.2. TiNivo-2
5.3. CONTACT-03
5.4. Entinostat in Combination with Nivolumab/Ipilimumab
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Clinical Trial Identifier | Histology | Line | Phase | Treatment Arm(s) | Accrual | Primary Endpoint(s) | Results |
---|---|---|---|---|---|---|---|
NCT02996110 FRACTION-RCC (track 2) | ccRCC | ≥2 | II | Nivolumab + Ipilimumab (in ICI-pretreated) | 46 | ORR, DOR, PFS rate at 24 weeks | ORR 17.4%, DCR 58.7% mDOR 16.4 months PFS rate at 24 weeks 43.2% mPFS 3.7 months mOS 23.8 months Grade 3–4 TRAEs 28.3% |
NCT03203473 OMNIVORE (arm B) | ccRCC or nccRCC | ≥2 | II (adaptive design) | Nivolumab + Ipilimumab (two doses of Ipilimumab for non-responders to Nivolumab induction) | 57 | Proportion of non-responders to Nivolumab induction converted to response | ORR 4% DCR 50% mPFS 4.7 months OS rate at 18 months 79% Grade 3–4 TRAEs 25% |
NCT03117309 HCRN GU16-260 (part B) | ccRCC or nccRCC | 2 | II (adaptive design) | Nivolumab + Ipilimumab (for non-responders to Nivolumab 1st line therapy) | 35 | ORR | ORR 11.4% ORR by irRECIST 17.1% Grade 3–4 TRAEs 42.9% |
NCT02917772 TITAN-RCC (second-line subgroup) | ccRCC (only intermediate/poor risk by IMDC score) | ≥2 | II (adaptive design) | Nivolumab + Ipilimumab (2–4 doses of Ipilimumab for non-responders to Nivolumab induction) | 139 | ORR | ORR 17% DCR 38.9% |
NCT01984242 IMmotion150 (second-line part) | ccRCC or sRCC | 2 | II | Atezolizumab + Bevacizumab (in previously treated with first-line Atezolizumab monotherapy) | 44 | ORR, PFS, DOR (secondary endpoints of the whole trial) | ORR 25% mPFS 11.1 months |
NCT02501096 KEYNOTE-146 (RCC cohort) | ccRCC | ≥2 | II | Lenvatinib + Pembrolizumab (in ICI-pretreated) | 104 | ORR at week 24 by irRECIST | ORR at week 24 55.8% ORR 62.5% mDOR 12.5 months mPFS 12.2 months Grade 3–4 TRAEs 64% |
Clinical Trial Identifier | Histology | Line | Phase | Treatment Arm(s) | Primary Endpoint(s) | Recruitment Status | Target Accrual |
---|---|---|---|---|---|---|---|
NCT04904302 SNAPI | ccRCC | 2–3 (ICI in immediately preceding line) | II | Sitravatinib + Nivolumab | ORR and DCR at 24 weeks | Recruiting | 88 |
NCT04987203 TiNivo-2 | ccRCC | 2–3 | III | Tivozanib + Nivolumab vs. Tivozanib | PFS | Recruiting | 326 |
NCT04338269 CONTACT-03 | ccRCC or nccRCC | 2–3 (ICI in immediately preceding line) | III | Cabozantinib + Atezolizumab vs. Cabozantinib | PFS, OS | Active, not recruiting | 523 |
NCT03552380 HCRN GU17-326 | ccRCC or nccRCC | 2 (previously treated with Nivo/Ipi) | II | Entinostat + Nivolumab + Ipilimumab | RP2D (safety lead-in), ORR | Active, not recruiting | 18 |
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Sammarco, E.; Manfredi, F.; Nuzzo, A.; Ferrari, M.; Bonato, A.; Salfi, A.; Serafin, D.; Zatteri, L.; Antonuzzo, A.; Galli, L. Immune Checkpoint Inhibitor Rechallenge in Renal Cell Carcinoma: Current Evidence and Future Directions. Cancers 2023, 15, 3172. https://doi.org/10.3390/cancers15123172
Sammarco E, Manfredi F, Nuzzo A, Ferrari M, Bonato A, Salfi A, Serafin D, Zatteri L, Antonuzzo A, Galli L. Immune Checkpoint Inhibitor Rechallenge in Renal Cell Carcinoma: Current Evidence and Future Directions. Cancers. 2023; 15(12):3172. https://doi.org/10.3390/cancers15123172
Chicago/Turabian StyleSammarco, Enrico, Fiorella Manfredi, Amedeo Nuzzo, Marco Ferrari, Adele Bonato, Alessia Salfi, Debora Serafin, Luca Zatteri, Andrea Antonuzzo, and Luca Galli. 2023. "Immune Checkpoint Inhibitor Rechallenge in Renal Cell Carcinoma: Current Evidence and Future Directions" Cancers 15, no. 12: 3172. https://doi.org/10.3390/cancers15123172
APA StyleSammarco, E., Manfredi, F., Nuzzo, A., Ferrari, M., Bonato, A., Salfi, A., Serafin, D., Zatteri, L., Antonuzzo, A., & Galli, L. (2023). Immune Checkpoint Inhibitor Rechallenge in Renal Cell Carcinoma: Current Evidence and Future Directions. Cancers, 15(12), 3172. https://doi.org/10.3390/cancers15123172