TRINOVA‐2.

Study characteristics
Methods	Randomised, double‐blind, placebo‐controlled phase 3 study from April 2011 to October 2013 in 69 sites in 16 countries (USA, Australia, Austria, Belgium, Canada, Denmark, France, Germany, Hong Kong, Hungary, Italy, New Zealand, Poland, Singapore, Slovakia, Switzerland, Taiwan, UK)
Participants	223 women with PR ROC Inclusion criteria Histologically or cytologically confirmed epithelial ovarian, primary peritoneal, or fallopian tube cancer ≥ 18 years of age One prior platinum‐based chemotherapeutic regimen for primary disease containing carboplatin, cisplatin, or another organoplatinum compound Radiographically documented disease progression Adequate bone marrow and organ function Exclusion criteria Platinum‐free interval > 12 months from their last platinum based therapy Major surgery within the last 4 weeks or still recovering from prior surgery Prior treatment with more than 3 regimens of anti‐cancer therapy for epithelial ovarian, primary peritoneal or fallopian tube cancer Prior treatment with PLD or any anthracycline‐based or mitoxantrone‐based chemotherapy CNS metastases
Interventions	Intervention IV PLD 50 mg/m2 once every 4 weeks plus weekly IV trebananib 15 mg/kg Control IV PLD 50 mg/m2 once every 4 weeks plus weekly IV placebo
Outcomes	Primary outcome PFS Secondary outcomes OS ORR DoR
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Participants randomised, however method not specified
Allocation concealment (selection bias)	Unclear risk	Allocation concealment for mentioned
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind, placebo controlled study
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not mentioned. Outcomes were assessed using the RECIST criteria.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Patient flow chart included and all patients accounted for.
Selective reporting (reporting bias)	High risk	No study protocol available. Clinical trials.gov has only overall survival (OS) as secondary outcome. Overall response rate (ORR) and duration of response (DOR) are added as outcomes in results.
Other bias	Unclear risk	Sponsored by Amgen, the maker of the study drug

AE: adverse event; ALT: alanine amino transferase; ASCO: American Society of Clinical Oncology; AST: aspartate amino transferase; AUC: area under the curve; bd: twice daily; BEV: bevacizumab; BRCA: breast cancer antgen; CA125: cancer antigen 125; CAN: canfosfomide; CRs: complete responses; DCR: disease control rate; DoR: duration of response; DSMB: Data and Safety Monitoring Board; EC145: vintafolide; ECG: electrocardiogram; ECOG: Eastern Cooperative Oncology Group; FR: folate receptor; GCIG: Gynecologic Cancer Intergroup; G‐CSF: granulocyte colony stimulating factor; GEM: gemcitabine; HQL: Health‐related quality of life assessment; HR: hazard ratio; IV: intravenous; IVI:intravenous infusion; M200: volociximab; NCI‐CTCAE: National Cancer Institute Common Terminology Criteria for Adverse Events; NYHA: New York Heart Association; OLA: olaparib; ORR: objective (or overall) response rate; OS; overall survival; PAC: paclitaxel; PARP: Poly(ADP‐ribose) polymerase; PD: programmed death receptor; PDGF: platelet‐derived growth factor; PDGF‐R; platelet‐derived growth factor receptor; PD‐L: programmed death ligand; PFI: platinum‐free interval; PFS: progression‐free survival; PK: pharmacokinetic; PLD: peglyated liposomal doxorubicin; PPS; partially platinum‐sensitive; PR: platinum resistant (or refractory); PRs: partial responses; PS: platinum sensitive; PTT: prothrombin time; QoL: quality of life; RCT: randomised control trial; RECIST: Response Evaluation Criteria in Solid Tumours; ROC: recurrent/relpased ovarian cancer; SAE: serious adverse events; TBD: trabectedin; Tc: technetium; TOP: topotecan; TTP: time‐to‐progression; VTX‐2337: motolimod.