Table 2.

Prospective clinical studies with combined drug therapies in mCRPC patients.

Drugs	Inclusion Criteria	Objectives	N	Phase	Findings [Ref]
PARPi Veliparib + Chemo. (PTX + CBDCA)	advanced solid tumors treated with ≤3 prior regimens, BRCA status not mandated	P. obj.: side effects Recommended phase II dose S. obj.: ORR	73	1	22 PR (1 in mCRPC pt) and 5 CR. Overall good tolerability Chemo. PK was not affected by PARPi [27]
ARSi Abiraterone + PARPi Veliparib	mCRPC, up to two prior chemotherapy regimens	P. obj.: PSA and RR, ETS response prediction; S. obj.: PFS, biomarkers	148	2	Arm A (ARSi) vs. Arm B (combo): no difference in wt pts; pts with DDR defects vs. wt: significantly better outcomes [28]
Anti-PD-L1 Durvalumab + PARPi Olaparib	Prior 1-2 ARSi; no preplanned DDR prescreening	P. obj.: clinical efficacy; S. obj.: ORR, PSA response, DDR status, biomarkers	17	2	9 /17 with PSA response, 4 of whom also disease response (large part of responders had DDRgm) [29]
PSMA-targeted CAR-T cells + IL-2	mCRPC	P. obj.: safety of PSMA-targeting with transduced T cells S. obj.:PSA response	5	1	2 PR with PSA response [30]

Abbreviations: N, size; D, design; PARPi, poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitor; Chemo., chemotherapy; PK, pharmacokinetics; PR, partial response; CR, complete response; ARSi, androgen receptor signaling inhibitor; P. obj., primary objectives; RR, response rate; ETS, a fusion gene; S. obj., secondary objectives; PFS, progression-free survival; mCRPC, metastatic castration-resistant prostate cancer; wt, wild-type tumors; DDR, DNA damage repair; ORR, Objective response rate; anti-PD-L1, anti-programmed cell death protein-1 ligand; DDRgm, DNA damage repair gene mutations; PSMA, prostate-specific membrane antigen; CAR-T cells, chimeric antigen receptor-T cells; IL-2, Interleukin-2.