Table 1 Novel regimens under investigation—prostate cancer highlights from ASCO 2023

[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