Table 1.

PARP-inhibitor combination treatments in clinical development.

Combination strategy	Agents	Trial phase	ClinicalTrials.gov identifier	Preclinical rationale	Clinical activity data	Patient population
Akt inhibition	Ipatasertib + rucaparib	I/II	NCT03840200	PARP inhibition activates Akt to promote cell survival	–	mCRPC, post-ARAT
Antiangiogenic agents	Cediranib + olaparib	II	NCT02893917	Reduced DDR gene expression with hypoxia/cediranib	–	At least second-line mCRPC
AR targeting	Enzalutamide + talazoparib	III	NCT03395197	Reduced DDR gene expression with antiandrogen therapies	Negative: veliparib Positive for PFS: olaparib	First-line mCRPC
	Abiraterone + olaparib	III	NCT03732820			First-line mCRPC
	Abiraterone + niraparib	III	NCT03748641			First-line mCRPC; biomarker stratified
	Abiraterone + olaparib	II	NCT03012321			First-line mCRPC + DDR alteration
DNA-damaging agents	Temozolomide + talazoparib	I/II	NCT04019327	Enhanced DNA damage	Negative: veliparib	mCRPC post-ARAT
DNA-repair combinations	AZD6738 + olaparib	II	NCT03787680	Synergy in cell lines lacking ATM-mediated survival pathways	–	Second-line mCRPC; stratified for DDR alterations
Immunotherapy	Durvalumab + olaparib	II	NCT03810105	Enhanced immunogenicity in combination	Positive for response: durvalumab Phase I activity: pembrolizumab	Biochemical recurrence postprostatectomy + DDR alteration
	Pembrolizumab + olaparib	III	NCT03834519			mCRPC post-ARAT ± taxane chemotherapy
	Nivolumab + rucaparib	II	NCT03338790			mCRPC
	JNJ-63723283 + niraparib	I/II	NCT03431350			mCRPC post-1–2 ARAT
	Nivolumab + rucaparib	I/II	NCT03572478			mCRPC, at least post-ARAT
Radionuclides	Ra-223 + niraparib	IB	NCT03076203	Increased DNA damage	–	Bone-metastatic CRPC, at least post-ARAT
	Ra-223 + olaparib	I/II	NCT03317392			Bone-metastatic CRPC
	177Lu-PSMA + olaparib	I	NCT03874884			mCRPC post-ARAT + taxane chemotherapy
Radiotherapy	IMRT, GnRH agonist + niraparib	II	NCT04037254	Increased DNA damage	–	High-risk localized prostate cancer
Testosterone	Bipolar testosterone enanthate/cypionate + olaparib	II	NCT03516812	DNA damage with bipolar androgen therapy	–	mCRPC post-ARAT; enriched for DDR alterations

¹⁷⁷Lu-PSMA, ¹⁷⁷lutetium-prostate-specific membrane antigen; Akt, protein kinase B; AR, androgen receptor; ARAT, androgen-receptor axis-targeted therapy; ATM, ataxia–telangiectasia mutated; DDR, DNA-damage repair; DNA, deoxyribonucleic acid; GnRH, gonadotropin-releasing hormone; IMRT, intensity-modulated radiation therapy; mCRPC, metastatic castration-resistant prostate cancer; PARP, polyadenosine-diphosphate-ribose polymerase; PFS, progression-free survival; Ra-223, radium-223 dichloride.