Introduction
Prostate
Reference number | Phase | Intervention | n | Population | Notes |
---|---|---|---|---|---|
[3] (PSMAddition) | 3 (active) | 177Lu-PSMA-617 every 6 weeks up to 6 cycles + SOC (ARPI + ADT) | 1126 (planned) | mCSPC with PSMA positive disease and without rapid tumor progression, first-line | Primary endpoint: rPFS PSMA positivity determined by 68Ga-PSMA-11 PET/CT |
[4] (BXCL701) | 2b (active) | BXCL701 (d1-14) + pembrolizumab (d1) given over 21 day cycles | 60 (planned) | mCRPC with small cell neuroendocrine phenotype, progression on at least one line of prior cytotoxic therapy | Primary endpoint: response rate BXCL701 is a dipeptidyl peptidase inhibitor theorized to trigger inflammasome and affect immune priming Comparison arm is BXCL701 monotherapy |
[5] (PRIME-CUT) | 2 | Docetaxel (two cycles) followed by cemiplimab (d1) given over 21 day cycles | 20 | mCSPC, first-line therapy | Primary endpoint: undetectable PSA at 6 months Primary endpoint not met (10% compared to prespecified historical rate of 32%) |
[6] (MAVERICK) | 2 (active) | Abivertinib (200 mg BID) + abiraterone (1000 mg qd) | 100 (planned) | mCRPC with HSD3B1(1245C) allele, two cohorts (abiraterone-naive and abiraterone-progressing) | Primary endpoint: 6-month rPFS HSD3B1(1245C) allele present in up to 50% of patients. Missense in corresponding enzyme causes up-regulation in rate-limiting step of extragonadal androgen biosynthesis Abivertinib is a TKI that inhibits phosphorylation of the above enzyme |
[7] (talazoparib/temozolomide) | 1b/2 (phase 1b accrual complete, phase 2 active) | Talazoparib (d1-6) + temozolomide (d2-8) given over 28 day cycles | 13 (phase 1) 55 (phase 2, planned) | mCRPC without DNA damage repair mutations, progression on at least one ARPI | Primary objective (phase 1): safety. Hematologic toxicity was identified as the DLT Primary endpoint (phase 2): overall response rate |
[8] (COMRADE) | 1/2 (phase 1 accrual complete,, phase 2 active) | Olaparib (200 mg BID) + radium-223 (every 4 weeks × 6 cycles) | 12 (phase 1) 133 (phase 2, planned) | mCRPC with ≥ 2 bone metastasis, any line | Primary objective (phase 1): determination of MTD Primary endpoint (phase 2): rPFS Any HRR status allowed in this study |
[9] (DUET) | 1/2 (active) | Radium-223 (weeks 0, 4, 8) alternating with 177Lu-PSMA-617 (weeks 6, 12) | 8 (planned) | mCSPC with low volume (2–5 bone metastases, 0–3 lymph node metastases) and PSA doubling time < 6 months, occurring following prior curative intent treatment (surgery or radiation) | Primary objective: feasibility/safety of radium-223 alternating with 177Lu-PSMA-617 |
[10] (tildrakizumab) | 1/2 (active) | Tildrakizumab + abiraterone acetate | 10 (phase 1, planned) 25 (phase 2, planned) | mCPRC, prior progression on ADT + abiraterone and/or enzalutamide | Primary objective (phase 1): MTD and RP2D determination Primary endpoint (phase 2): overall response rate Tildrakizumab is an IL-23 inhibitor. IL-23 blockade has been shown to reverse resistance to ARPI in vivo |
[11] (CABIOS) | 1b (active, interim analysis) | Cabozantinib [20 mg or 40 mg qd] + nivolumab (every 4 weeks) + abiraterone (1000 mg qd) | 17 (interim) | mCSPC, de novo or recurrent without prior abiraterone or docetaxel | Primary endpoint: safety and tolerability At median follow-up of 12.8 months during interim analysis, 9 patients remain on study with 1 withdrawal, 4 discontinuations due to toxicity, and 3 discontinuations due to progression |
[12] (LuPARP) | 1 (active, interim analysis) | 177Lu-PSMA-617 (every 6 weeks × 6 cycles) + olaparib | 48 (planned) | mCRPC and high PSMA expression (SUVmax ≥ 15 at site of disease and ≥ 10 at other sites), prior therapy allowed | Primary objective: establishing DLT and RP2D Interim analysis showing most common G1-2 toxicity was xerostomia (83%), nausea, (62%), fatigue (34%) and constipation (31%). 18/29 patients in interim analysis with at least 50% reduction in PSA |
[13] (ProSperA) | 1 (active) | CC-1 | 24–42 (dose-escalation, planned) 14 (dose expansion, planned) | Low-risk biochemical recurrence after prostatectomy or radiation | Primary objective: identification of MTD and RP2D CC-1 is a PSMAxCD3 bispecific antibody. CC-1 is also being evaluated in a separate phase I trial for mCRPC |
[14] (PSCA CAR-T) | 1 | PSCA-targeted 4-1BB co-stimulated CAR-T | 14 | mCRPC, progression after at least 1 prior ARPI | Primary objective: establishing DLT (cystitis) Lymphodepleting chemotherapy was necessary for greater CAR T expansion; lower doses of lymphodepleting chemotherapy reduced toxicity without clear impact on expansion |
Urothelial carcinoma
Reference number | Phase | Intervention | n | Population | ORR | mPFS | mOS | Safety |
---|---|---|---|---|---|---|---|---|
[17] EV103 | 1b/2 | Enfortumab vedotin + Pembrolizumab | 45 | Patients with metastatic urothelial carcinoma who were cisplatin ineligible | 73.3% (58.1–85.4) | 12.7 mos | 26.1 mos | 64.4% with Grade III toxicity, primarily elevated lipase, maculo-papular rash, and fatigue |
[18] THOR | 3 | Erdafitinib versus chemotherapy (investigator’s choice) in patients with FGFRalt | 266 | Patients with urothelial carcinoma with FGFRalt on 2nd or 3rd line therapy | 45.6 versus 11.5 | 5.6 versus 2.7 | 12.1 versus 7.8 mos | Serious treatment-related events 13% with Erdafitinib versus 24% in chemotherapy arm |
[19] Norse | 2 | Erdafitinib compared to Erdafitinib + Cetrelimab in metastatic urothelial carcinoma with presence of FGFRalt | 87 | Patients with metastatic urothelial carcinoma with FGFRalt and are cisplatin ineligible | 54.5% in combination versus 44.2% in ERDA alone | 10.97 mos versus 5.62 mos | - | 1 death in combination group from pulmonary failure, otherwise no added toxicity with addition of Cetrelimab to ERDA |