Table 2:

Select completed and ongoing clinical trials targeting the tumour–nerve axis

	Therapy	Target^*	Phase	Actual or target accrual	Primary endpoint	Status	Outcome	Reference

H3K27M spinal cord glioma	ONC201	DRD2/DRD3 antagonist	Phase 2	76	Progression-free survival	Ongoing	8 of 12 patients alive at <12 months median follow-up	NCT02525692
H3K27M diffuse midline glioma	ONC201	DRD2/DRD3 antagonist	Phase 2	95	Objective response rate	Ongoing	No dose-limiting toxicity	NCT03295396
Thalamic H3K27M glioma	ONC201	DRD2/DRD3 antagonist	Phase 2	95	Objective response rate	Ongoing	26·3% 6-month progression-free survival	NCT03295396
Recurrent glioblastoma	ONC201	DRD2/DRD3 antagonist	Phase 2	17	Progression-free survival	Completed	No difference in 6-month progression-free survival	NCT02525692
Neuroendocrine tumours	ONC201	DRD2/DRD3 antagonist	Phase 2	25	Tumour response	Ongoing	56% progressed	NCT03034200
Paediatric diffuse intrinsic pontine glioma	ONC201	DRD2/DRD3 antagonist	Phase 1	130	Recommended phase 2 dose	Ongoing	Not reported	NCT03416530
Endometrial cancer	ONC201	DRD2/DRD3 antagonist	Phase 2	30	Progression-free survival	Ongoing	Not reported	NCT03485729
Acute myeloid leukaemia	ONC101	DRD2/DRD3 antagonist	Phase 1	20	Dose-limiting toxicity	Ongoing	Not reported	NCT03932643
Ovarian, fallopian tube, or primary peritoneal cancer	ONC201	DRD2/DRD3 antagonist	Phase 2	62	Dose-limiting toxicity, adverse events, objective response rate, progression-free survival	Ongoing	Not reported	NCT04055649
Recurrent and rare CNS tumours	ONC206	DRD2 antagonist	Phase 1	102	Dose-limiting toxicity	Ongoing	Not reported	NCT04541082
Paediatric high-grade glioma	INCB7839	ADAM10/17 inhibitor	Phase 1	28	Adverse events	Ongoing	Not reported	NCT04295759
Glioblastoma	Talampanel	AMPAR regulator	Phase 2	72	Overall survival	Completed	Improved overall survival compared with historical controls	NCT00943826, NCT00689221, NCT00813943, NCT00884741
Glioblastoma	Memantine, mefloquine, metformin	NMDAR regulator	Phase 1/2	85	Dose-limiting toxicity	Completed	Dose-limiting toxicity: dizziness, gastrointestinal symptoms, lymphopenia	NCT01430351
Glioblastoma	Memantine	NMDAR regulator	Phase 2	4	Overall survival	Terminated	Not reported	NCT01260467
Glioblastoma	Meclofenamic acid	NSAID⁶⁴	Phase 1/2	72	Dose-limiting toxicity, progression-free survival	Ongoing	Not reported	EudraCT2021-000708-39
Glioma	Talampanel	AMPAR inhibitor	Phase 2	30	Progression-free survival	Terminated	Early termination due to futility	NCT00062504
Ovarian, primary peritoneal, or fallopian tube cancer	Propranolol, chemotherapy	β-adrenergic antagonist	Phase 1	32	Feasibility	Completed	Not reported	NCT01504126
Ovarian cancer	Propranolol	β-adrenergic antagonist	Phase 1	26	Feasibility	Completed	Improved quality of life	NCT01308944
Colorectal cancer	Propranolol, COX2 inhibitor	β-adrenergic antagonist	Phase 3	34	3-year recurrence	Completed	No difference in recurrence	NCT00888797
Breast cancer	Propranolol, COX2 inhibitor	β-adrenergic antagonist	Phase 2	38	Pro-metastatic cell markers	Completed	Decreased pro-metastatic and invasive markers	NCT00502684
Breast cancer	Propranolol, chemotherapy	β-adrenergic antagonist	Phase 2	10	Compliance	Ongoing	Not reported	NCT01847001
Breast cancer	Propranolol	β-adrenergic antagonist	Phase 2	60	Gene expression biomarkers	Completed	Reduced metastatic potential	ACTRN12615000889550
Pancreatic cancer	Propranolol etodolac	β-adrenergic antagonist/COX-2 Inhibitor	Phase 2	210	Recurrence	Ongoing	Not reported	NCT03838029
Pancreatic cancer	Bethanechol	Muscarinic agonist	Phase 1	18	Change in Ki-67	Ongoing	Not reported	NCT03572283
Cancer pain	Tanezumab	Antibody against NGF	Phase 3	156	Change in pain	Completed	Not reported	NCT00545129 NCT02609828
Cancer pain	Resiniferatoxin	Capsaicin analogue	Phase 1	45	Safety	Ongoing	Not reported	NCT00804154
Melanoma	Propranolol, pembrolizumab	β-adrenergic antagonist	Phase 1	9	Safety	Completed	No dose-limiting toxicity; objective response rate 78%	NCT03384836
Bladder cancer	Propranolol, pembrolizumab	β-adrenergic antagonist	Phase 2	25	Objective response rate	Ongoing	Not reported	NCT04848519

COX-2=cyclooxygenase 2. DRD2=dopamine receptor D2. DRD3=dopamine receptor D3. NGF=nerve growth factor. NSAID=non-steroidal anti-inflammatory drug.

Where multiple therapies are listed, this column relates only to drugs targeting the tumour–nerve axis.