Table 2.

Dose-limiting toxicities.

Patient	MedDRA Preferred Term	CTCAE Grade	Changes in Solitomab Infusion	Resolved	Dose at Time of DLT (μg/day)	Treatment Schedule
1	AST increased	4	None	Yes	1	A
	ALT increased	4	None	Yes
	Glutamate dehydrogenase increased	4	None	Yes
2	AST increased	3	Discontinued	Yes	10	A
3	Gamma-glutamyl transferase increased	4	Discontinued	Yes	24	B
4	Diarrhea	3	Discontinued	Yes	24	B
5	Abdominal pain	3	Discontinued	Yes	24	Bx
	Diarrhea	3	Discontinued	Yes
6	Diarrhea	3	Discontinued	Yes	48	Bx
7	AST increased	3	Discontinued	Yes with sequelae	12	Bx
8	Blood bilirubin increased	3	Discontinued	Yes	96	Bx
9	Diarrhea	4	Discontinued	Yes	96	Bx
10	AST increased	4	Discontinued	Yes with sequelae	12	Bz1
	ALT increased	4	Discontinued	Yes
11	AST increased	4	None	Yes	12	Bz1
12	Blood bilirubin increased	3	Discontinued	Yes	24	C
13	Diarrhea	3	Discontinued	Yes with sequelae	24	C
14	Diarrhea	3	Discontinued	Yes	48	D
15	Supraventricular tachycardia	3	Discontinued	Yes	48	D

Abbreviations: AST, aspartate aminotransferase; ALT, alanine aminotransferase; CTCAE, Common Terminology Criteria for Adverse Events; MedDRA, Medical Dictionary for Regulatory Activities; DLT, dose-limiting toxicity.

^*Treatment schedules B, C, and D could be performed in parallel as independent groups.

^†Event was not considered a DLT by the investigator per protocol provision (see Methods) given the rapid normalization of liver abnormalities and the absence of clinical signs and symptoms. The patient had increased liver parameters at baseline following anticoagulation therapy, which was discontinued at study start. Liver parameters had normalized before solitomab administration but increased again once anticoagulation treatment was restarted. These events triggered specific protocol amendments that resulted in modifications of the dose and dosing schedules and the definition of DLT (Supplementary Data).

^‡Resolution with sequale indicates that resolution of the DLT to grade 1 or baseline level did not occur until the end of the study. In patient 7, the AST increase resolved to grade 2 at the end of study. In patient 10, the AST increase resolved to grade 3 at the end of the study. In patient 13, diarrhea resolved to grade 2 at the end of the study and subsequently received other chemotherapy.

^§This DLT was not documented as an AE by the investigator due to the absence of clinical signs and symptoms.