Table 4.
Ongoing clinical trials exploring combined TGFβ and immune checkpoint inhibition that have yet to post results.
| Anti-TGFβ and ICI medications | Additional therapy | NCT identifier | Phase | Notes |
|---|---|---|---|---|
| Colorectal cancer | ||||
| Vactosertib + Pembrolizumab |
– | NCT03844750 | 2 | Post-chemotherapy, pre-operative treatment for patients with resectable liver metastases |
| Bintrafusp alfa | CV301 N-803 NHS-IL12 |
NCT04491955 | 2 | Locally advanced or metastatic MSS small intestine or colorectal adenocarcinoma ICI-naïve |
| Pancreatic cancer | ||||
| SHR-17011 | Gemcitabine/Albumin-Paclitaxel | NCT04624217 | 1b/2 | Advanced PDAC |
| NIS793 + Spartalizumab |
nab-Paclitaxel/Gemcitabine | NCT04390763 | 2 | Untreated metastatic PDAC |
| Bintrafusp alfa | Stereotactic Body Radiation Therapy M9241 |
NCT04327986 | 1/2 | Advanced PDAC |
| Biliary tract cancer | ||||
| Bintrafusp alfa | – | NCT03833661 | 2 | Second-line treatment in advanced disease |
| – | NCT04727541 | 2 | Neoadjuvant treatment for resectable disease | |
| Hypofractionated Radiation Therapy | NCT04708067 | 1 | Advanced intrahepatic cholangiocarcinoma | |
| Gastroesophageal cancers | ||||
| Vactosertib + Durvalumab |
– | NCT04893252 | 2 | Heavily pretreated, metastatic disease |
| Bintrafusp alfa | Paclitaxel | NCT04835896 | 1b/2 | Second-line treatment for recurrent/metastatic disease |
| Paclitaxel Carboplatin External Beam Radiotherapy |
NCT04595149/NCT04481256 | 2 | Nonresectable esophageal or gastro-esophageal junction SCC | |
| Primary lung cancers | ||||
| Vactosertib + Durvalumab |
– | NCT03732274 | 1b/2a | Advanced, platinum-treated NSCLC |
| Vactosertib + Pembrolizumab |
– | NCT04515979 | 2 | Advanced, untreated, PD-L1-expressing NSCLC |
| Bintrafusp alfa | – | NCT04560686 | 2 | Resectable, untreated NSCLC |
| Cisplatin/Etoposide Carboplatin/Paclitaxel Cisplatin/Pemetrexed Intensity Modulated Radiation Therapy |
NCT03840902 | 2 | Nonresectable Stage III NSCLC | |
| Cisplatin Carboplatin/Pemetrexed/Etc. |
NCT03840915 | 1/2 | Stage IV NSCLC | |
| Docetaxel | NCT04396535 | 2 | Advanced NSCLC that has progressed on prior anti-PD-1/PD-L1 and chemotherapy | |
| Pemetrexed Carboplatin Cisplatin |
NCT04971187 | 2 | Nonresectable locally advanced or metastatic, Tyrosine Kinase Inhibitor-Resistant, EGFR-Mutant NSCLC | |
| Topotecan Temozolomide |
NCT03554473 | 2 | Relapsed small cell lung cancer | |
| – | NCT05005429 | 2 | Previously treated, advanced or metastatic malignant pleural mesothelioma | |
| Standard of Care Chemotherapy | NCT04297748 | 1/2 | Advanced NSCLC, bio-distribution study | |
| Breast cancer | ||||
| Bintrafusp alfa | – | NCT04489940 | 2 | HMGA2-expressing TNBC |
| – | NCT03620201 | 1 | Stage II/III HER2+ breast cancer | |
| Radiation Therapy | NCT03524170 | 1 | Metastatic, HR+, HER2- breast cancer | |
| Eribulin Mesylate | NCT03579472 | 1 | Metastatic TNBC | |
| NHS-IL12 Radiation Therapy |
NCT04756505 | 1 | Metastatic, HR+, HER2- breast cancer | |
| Gynecologic malignancies | ||||
| Bintrafusp alfa | – | NCT04246489 | 2 | Non-resectable, platinum-treated advanced cervical cancer |
| Cisplatin Carboplatin Paclitaxel Bevacizumab Radiation Therapy |
NCT04551950 | 1 | Locally advanced/advanced disease | |
| Carboplatin Paclitaxel |
NCT05145569 | 1 | Advanced ovarian cancer | |
| HNSCC | ||||
| Galunisertib + Unspecified anti-PD-1 antibodies |
Gemcitabine Cisplatin Radiation Therapy |
NCT04605562 | 2 | High-risk, locoregionally advanced nasopharyngeal carcinoma |
| Bintrafusp alfa | – | NCT04428047 | 2 | Untreated, resectable HNSCC |
| TriAd vaccine N-803 |
NCT04247282 | 1/2 | Untreated, resectable, non-HPV-associated HNSCC | |
| Stereotactic Body Radiation Therapy | NCT04220775 | 1/2 | Recurrent or second primary HNSCC | |
| – | NCT04396886 | 2 | Previously treated, recurrent or metastatic non-keratinizing nasopharyngeal carcinoma | |
| Other HPV-associated cancers | ||||
| Bintrafusp alfa | PRGN-2009 | NCT04432597 | 1/2 | Locally advanced or metastatic HPV-positive cancers |
| Urologic cancers | ||||
| Vactosertib + Durvalumab |
– | NCT04064190 | 2 | Urothelial cancer refractory to anti-PD-1/PD-L1 |
| Bintrafusp alfa | – | NCT04349280 | 1b | Locally advanced or metastatic, platinum-treated urothelial cancer |
| – | NCT04878250 | 2 | Neoadjuvant treatment for resectable urothelial carcinoma | |
| NHS-IL12 Stereotactic Body Radiation Therapy |
NCT04235777 | 1 | Metastatic, non-prostate genitourinary malignancies | |
| NHS-IL12 Docetaxel |
NCT04633252 | 1/2 | Metastatic prostate cancer | |
| CV301 PROSTVAC-V PROSTVAC-F |
NCT03315871 | 2 | Recurrent prostate cancer | |
| BN-Brachyury Vaccine N-803 Epacadostat |
NCT03493945 | 1/2 | Castration-resistant prostate cancer | |
| Neurologic malignancies | ||||
| Bintrafusp alfa | – | NCT05012098 | 2 | Previously treated, recurrent or metastatic olfactory neuroblastoma |
| Pimasertib | NCT04789668 | 1/2 | Metastatic brain lesions originating from extracranial tumors | |
| Thymus cancer | ||||
| Bintrafusp alfa | – | NCT04417660 | 2 | Platinum-treated thymoma or thymic carcinoma |
| Sarcoma | ||||
| Bintrafusp alfa | Doxorubicin | NCT04874311 | 2 | Advanced soft-tissue sarcoma |
| NHS-IL12 | NCT04303117 | 1/2 | Advanced Kaposi sarcoma | |
| Multi-cancer studies | ||||
| SAR439459 + Cemiplimab |
– | NCT03192345 | 1 | Nonresectable, advanced or metastatic solid tumors |
| Bintrafusp alfa | – | NCT02517398 | 1 | Locally advanced or metastatic solid tumors |
| SX-682 CV301 |
NCT04574583 | 1/2 | Locally advanced or metastatic solid tumors | |
| Entinostat NHS-IL12 |
NCT04708470 | 1/2 | Phase 1: locally advanced or metastatic HPV-associated malignancies or MSS small bowel or colorectal cancers Phase 2: locally advanced or metastatic checkpoint-refractory HPV-associated malignancies or MSS small bowel or colorectal cancers |
|
| M6223 | NCT04457778 | 1 | Nonresectable, locally advanced or metastatic solid tumors | |
| Feladilimab | NCT02723955 | 1 | Advanced or recurrent solid tumors | |
| – | NCT05061823 | 3 | Prospective long-term safety study | |
| – | NCT04267861 | – | Retrospective, observational long-term safety study | |
Abbreviations: Transforming Growth Factor β (TGFβ); Immune checkpoint inhibitor (ICI); Programmed cell death protein 1 (PD-1); PD-1 ligand 1 (PD-L1); Microsatellite stable (MSS); Pancreatic ductal adenocarcinoma (PDAC); Squamous cell carcinoma (SCC); Non-small cell lung cancer (NSCLC); High-mobility group AT-hook 2 (HMGA2); Triple negative breast cancer (TNBC); Human epidermal growth factor receptor 2 (HER2); Hormone receptor (HR); Head and neck squamous cell carcinoma (HNSCC); Human papillomavirus (HPV).