Table 2.
Immuno-oncology drugs in clinical development for prostate cancer in the context of bone metastasis.
| ASSET NAME | TARGET(S) | MODA-LITY | TRIAL | SELECTED ELIGIBILITY CRITERIA AND OUTCOME MEASUREMENT |
TRIAL STATUS |
DEVELOPER/SPONSOR | |
|---|---|---|---|---|---|---|---|
| INCLUSION | OUTCOME | ||||||
| Imifoplatin (PT-112) |
Pyrophos-phate-platinum conjugate | Small molecule | NCT02266745, ph1/2 | Progressive disease measured by physical examination or imaging (RECIST v1.1 or PCWG3 or by informative tumor markers) | Secondary: rPFS, disease control rate, objective response rate, duration of response, OS | Recruiting | Promontory Therapeutics/ Pfizer, EMD Serono |
| P-PSMA-101 | PSMA | CAR-T |
NCT04249947, ph1 (in combination with rimiducid) |
Measurable disease by RECIST 1.1 or bone only metastases with measurable PSA | Overall response rate, percentage of patients with complete or partial response | Recruiting | Poseida Therapeutics |
| Pasotuximab (BAY2010112) | PSMAxCD3 | Bispecific antibody | NCT01723475, ph1 | Appearance of one more new lesions in bone scan | Secondary: Tumor and PSA response | Completed | Bayer |
| MGC018 | B7-H3 | Antibody-drug conjugate |
NCT03729596, ph1/2 (combination with anti-PD-1 will not enroll) NCT05551117, ph2/3 |
In prostate cancer cohort, patients with bone only disease are eligible One or more metastatic lesion, present MRI, CT or bone scan |
Secondary: OS, PFS, rPFS, response rate Primary: rPFS |
Active, not recruiting Not yet recruiting |
MacroGenics |
| DS-7300a | B7-H3 | Antibody-drug conjugate | NCT04145622, ph1/2 | CRPC participants with bone only disease may be eligible on a case-by-case basis | Anti-tumor activity | Recruiting | Daiichi Sankyo |
| MVI-118 | Encode AR LBD |
DNA vaccine |
NCT02411786, ph1 (+/- GM-CSF) |
Soft tissue and/or bone metastases by radiographic imaging | Secondary: Median and 18-month PFS | Completed | Madison Vaccines |
| MVI-816 (pTVG-HP) | Encode AR LBD |
DNA vaccine |
NCT01706458, ph2 (in combination with sipuleucel-T) NCT02499835, ph1/2 (in combination with pembrolizumab) |
Soft tissue and/or bone metastases in imaging studies | Secondary: PFS, time to radiographic progression | Completed Active, not recruiting |
Madison Vaccines |
| Recombinant Ad5 vaccine | PSA/MUC-1/brachyury | Virus vaccine | NCT03481816, ph1 | Metastatic bone disease in an imaging study | Secondary: OS, PFS | Completed | ImmunityBio/NCI |
| Rilimogene glafolivec | PSA, CD48, CD80, ICAM1, KLK3 | Virus vaccine |
NCT01322490, ph3 (+/- GM-CSF) |
Radiological progression (new or growing bone metastases or new/enlarging lymph node disease) | Primary: OS, number alive without event after 6 months (event is two new bone lesions or other metastases) | Completed | Bavarian Nordic |
| Bintrafusp alfa (M7824) and M9241 |
PD-L1- TGFβ NHS- IL12A |
Fusion protein Fusion protein |
NCT04633252, ph1/2 (in combination with androgen deprivation therapy, prednisone and docetaxel) |
Metastatic disease, defined as at least one lesion on TC99 bone scan or at least one measurable lesion per RECIST 1.1. | Secondary: Radiographic response rates, radiographic and biochemical time to progression | Recruiting | Merck KGaA/NCI |
| Vudalimab (XmAb20717) |
PD-1 x CTLA-4 | Bispecific antibody |
NCT05005728, ph2 (in combination with carboplatin, cabazitaxel, olaparib |
Progression of bone disease (evaluable disease) or 2 or more new bone lesions by bone scan | Secondary: Objective response rate by PCWG3, bone scan and rPFS, duration of response | Recruiting | Vencor |
| Tremelimumab | CTLA-4 | Monoclo-nal antibody |
NCT03204812, ph2 (in combination with durvalumab) |
Evidence of metastatic disease to the bone seen in most recent bone scan, CT scan and/or MRI | Secondary: rPFS, median OS | Completed | Pfizer/MDA |
| BMS-986249 | CTLA-4 | Conditio-nally activated antibody |
NCT03369223, ph 1/2 (in combination with nivolumab) |
Measurable disease or metastatic disease documented by bone lesions in radionuclide bone scan | Secondary: PFS, overall response, duration of response | Recruiting | CytomX Therapeutics/Bristol-Myers Squibb |
| Epacadostat and MVA-BN Brachyury |
IDO1 TBXT |
Small molecule Protein |
NCT03493945, ph1/2 (in combination with M7824 and N-803) |
Radiographically proven metastatic or locally advanced solid tumor of any type | Secondary: PFS | Recruiting | Incyte/NCI Bavarian Nordic |
| Talabostat mesylate (BXCL701) |
DPP4, DPP8, DPP9, FAP | Small molecule |
NCT03910660, ph1/2 (in combination with pembrolizumab) |
RECIST 1.1 measurable disease or detectable bone metastases by whole body bone scintigraphy | Secondary: rPFS, median OS, duration of response | Recruiting | BioXcel Therapeutics |
| Dendritic cell vaccine | CTAG1B, MAGEC2, MUC1 | Cell vaccine | NCT02692976, ph2 | Bone disease progression defined by two or more new lesions in bone scan as described in PCWG2 criteria | Secondary: rPFS, OS | Completed | Radbound University |
| MB-105 | PSCA | CAR-T | NCT03873805, ph1 | Radiographic evidence of new metastatic foci in computed CT or bone scan | Secondary: rPFS, OS | Recruiting | Fortress Biotech/City of Hope Med Cent |
| Reolysin (pelareorep) | N/A | Virus |
NCT01619813, ph2 (in combination with docetaxel and prednisone) |
Metastatic or locally recurrent disease, clinically and/or radiologically documented disease | Primary: Disease progression, OS | Completed | Oncolytic Biotech |
“Developer” refers to the original developer/owner, “Stage” refers to the highest development stage. “Inclusion” and “Outcome” columns include selected parameters relevant in the context of bone metastasis. Detailed description of the drugs and the results are provided in the chapters below. All listed trials are for prostate cancer. AR, androgen receptor; B7-H3, B7 homolog 3; CAR-T, chimeric antigen receptor, T cell; CD, cluster of differentiation; CRPC, castration-resistant prostate cancer; CTAG1B, cancer/testis antigen 1B; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; DPP, dipeptidyl peptidase; FAP, fibroblast activation protein; ICAM 1, intracellular adhesion molecule 1; IL12A, interleukin 12 A; KLK3, kallikrein related peptidase 3; LBD, ligand binding domain; MAGEC2, MAGE family member C2; MRI, magnetic resonance imaging; MUC-1, mucin-1; OS, overall survival; PCWG3, prostate cancer working group 3; PD-1, programmed cell death 1; PD-L1, programmed death-ligand 1; PFS, progression-free survival; PSA, prostate-specific antigen; PSCA, prostate stem cell antigen; PSMA, prostate-specific membrane antigen; RECIST, response evaluation criteria in solid tumors; rPFS, radiographic progression-free survival; TBTX, T-box transcription factor T; TGFβ, transforming growth factor beta. N/A, Not available.