Table 3.
Current clinical trials combining PI3K-δ and -γ inhibitors with T-cell targeted therapies.
| Indication | PI3K Inhibitor | Synergy Drug | PI3K Isoform | Trial Phase | NCT Number | Immune Cell Biomarker | Solid or Hematologic |
|---|---|---|---|---|---|---|---|
| HNSCC, NSCLC, CRC, HCC | Copanlisib | Nivolumab | alpha and delta | Phase 1 | NCT03735628 | No | Solid |
| Unresectable or Metastatic MSS Solid Tumors | Copanlisib | Nivolumab | alpha and delta | Phase 1/2 | NCT03711058 | No | Solid |
| Indolent Lymphoma | Copanlisib | Nivolumab + Rituximab | alpha and delta | Phase 1 | NCT04431635 | No | Hematologic |
| R/R DLBCL and R/R PMBCL | Copanlisib | Nivolumab | alpha and delta | Phase 2 | NCT03484819 | Yes | Hematologic |
| Richter’s Transformation or Transformed Indolent Non-Hodgkin’s Lymphoma | Copanlisib | Nivolumab | alpha and delta | Phase 1 | NCT03884998 | Yes | Hematologic |
| Ann Arbor Stage III/IV Lymphoma, Metastatic/Recurrent Malignant Solid Neoplasm | Copanlisib | Ipilimumab + Nivolumab | alpha and delta | Phase 1 | NCT03502733 | No | Both |
| PD-1 refractory unresectable melanoma | Duvelisib | Nivolumab | delta and gamma | Phase I/2 | NCT04688658 | Yes | Solid |
| Stage IIB-IVB Mycosis Fungoides and Sezary Syndrome | Duvelisib | Nivolumab | delta and gamma | Phase 1 | NCT04652960 | Yes | Hematologic |
| Richter Syndrome or Transformed Follicular Lymphoma | Duvelisib | Nivolumab | delta and gamma | Phase 1 | NCT03892044 | Yes | Hematologic |
| Advanced Solid Tumors, NSCLC, Melanoma, HNSCC, TNBC, Adrenocortical Carcinoma, Mesothelioma, High-circulating MDSCs | Eganelisib (IPI-549) | Nivolumab | gamma | Phase 1 | NCT02637531 | Yes | Solid |
| ICI naïve, platinum refractory UCC | Eganelisib (IPI-549) | Nivolumab | gamma | Phase 2 | NCT03980041 | No | Solid |
| Breast Cancer, RCC | Eganelisib (IPI-549) | Atezolizumab | gamma | Phase 2 | NCT03961698 | Yes | Solid |
| NSCLC | Idelalisib | Pembrolizumab | delta | Phase 1/2 | NCT03257722 | Yes | Solid |
| R/R CLL, R/R low-grade B-cell NHLs | Idelalisib | Pembrolizumab | delta | Phase 2 | NCT02332980 | Yes | Hematologic |
| CRC, Endometrial Cancer, Melanoma, Head and Neck Cancer, Lung Cancer, MMR-deficient Tumors, Breast Cancer, Pancreatic Cancer, RCC, Solid Tumors, UC | Parsaclisib | Pembrolizumab | delta | Phase 1 |
NCT02646748 (Group B) |
Yes | Solid |
| Unresectable or Metastatic Solid Tumors | Parsaclisib | Retifanlimab (anti-PD-1) | delta | Phase 1 | NCT03589651 | No | Solid |
| Advanced HCC | SF1126 | Nivolumab | alpha, beta, delta, and gamma* | Phase 1 | NCT03059147 | No | Solid |
| CLL, B-cell NHL | TGR-1202 | Pembrolizumab | delta | Phase 1 | NCT03283137 | No | Hematologic |
NSCLC (Non-small Cell Lung Cancer); HNSCC (Head and Neck Squamous Cell Carcinoma; TNBC (Triple negative breast cancer); CLL (Chronic Lymphocytic Leukemia); CRC (Colorectal Cancer); HCC (Hepatocellular Carcinoma), RCC (Renal Cell Carcinoma); UC (Urothelial Carcinoma), NHL (Non-Hodgkin’s Lymphoma), MSS (Microsatellite Stable), R/R (relapsed/refractory); DLBCL (diffuse large B-cell lymphoma); PMBCL (primary mediastinal large B-cell lymphoma).
*Bromodomain-4 and PI3K inhibitor.