Table 2 Detailed characteristics of studies with OBD

[14]

Solid

Immunotherapy

Interleukin 2

13-cis Retinoic Acid

Interleukin 2

Phase I

OBD

DLT + IR

Consecutive/sequential cohorts

CR (WHO response criteria)

IR (changes of total T- and T-helper cell counts)

TTP, OS

[15]

Solid

Immunotherapy

Interleukin 12 Trastuzumab

Interleukin 12

Phase I

MTD

DLT

3 + 3

DLT + IR

CR (not specified)

IR (induction of systemic NK cell-derived cytokines)

[16]

Melanoma

Immunotherapy

Set of combination immunotherapies

Set of combination immunotherapies

Phase I/II

OBD

DLT + IR

CRM for two binary endpoints

IR (levels of peptide-reactive CD8+ cells)

[17]

Melanoma

Immunotherapy

Recombinant human IL-12

Melan-A and influenza peptides

Recombinant human IL-12

Phase I

OBD

Toxicity + IR

Other

CR

IR (cytotoxic lymphocyte response + cutaneous responses)

[18]

Solid

Metabolic therapy

Pegylated recombinant human arginase 1

Pegylated recombinant human arginase 1

Phase I

OBD

DLT + plasma arginine depletion

Modified fibonacci

CR (RECIST criteria)

PFS, OS

PK/PD

[19]

Melanoma

Metabolic therapy

High dose paracetamol

Carmustine

High dose paracetamol

Carmustine

Phase I

MTD

DLT

3 + 3

Toxicity + effects on GSH levels

CR

PK

[20]

Solid

Oncolytic Virus therapy

NV1020

NV1020

Phase I/II

MTD

DLT

Consecutive/sequential cohorts

DLT + CR

CR (RECIST criteria)

TTP, OS

PK

[21]

Solid

Radiotherapy

Carbon ion

Carbon ion

Phase I/II

OBD

DLT + local control rate

Other

OS, cause specific survival

[22]

Solid

Radiotherapy

Carbon ion

Carbon ion

Phase I

MTD

DLT

3 + 3

DLT + CR

CR (RECIST criteria)

PFS, OS

[23]

Solid

Radiotherapy

Carbon ion

Carbon ion

Phase I

OBD

DLT + tumor response at 6 months

Other

Local control

OS

[24]

Hematologic

Targeted therapy

Acadesine

Acadesine

Phase I/II

MTD

DLT

Modified fibonacci

DLT + CR

CR (IWG response criteria)

PK/PD

[25]

Hematologic

Targeted therapy

Venetoclax

Ibrutinib

Venetoclax

Ibrutinib

Phase I

OBD

DLT + ORR at 2 months

CRM for two binary endpoints

CR (Cheson modified criteria)

[26]

Solid

Targeted therapy

Angiotensin 1–7

Angiotensin 1–7

Phase I/II

OBD/MTD

DLT + response data for white, platelets and red blood cells

3 + 3

PK

[27]

Solid

Targeted therapy

Emactuzumab

Emactuzumab

Phase I

OBD/MTD

DLT + (PK profile + all response data)

3 + 3

CR (RECIST criteria)

Duration of clinically progression-free follow-up

PK/PD

[28]

Solid

Targeted therapy

Recombinant human thrombopoietin Carboplatin

Recombinant human thrombopoietin

Phase I/II

OBD

Biological response (platelet count response)

Consecutive/sequential cohorts

[29]

Solid

Targeted therapy

NGR-hTNF

Oxaliplatin Capecitabine

NGR-hTNF

Phase I

OBD/MTD

DLT + PK/PD (NGR-hTNF and sTNF receptors 1 and 2)

Consecutive/sequential cohorts

CR (RECIST criteria)

PFS

PK/PD

[30]

Solid

Targeted therapy

Eltrombopag

Doxorubicin

Ifosfamide

Eltrombopag

Phase I

MTD

DLT

Consecutive/sequential cohorts

Thrombocytopenia + platelet counts

PK/PD

[31]

Solid

Targeted therapy

NGR-hTNF

NGR-hTNF

Phase I

MTD

DLT

Consecutive/sequential cohorts

DLT + CR

CR (RECIST criteria)

PFS, OS

PK/PD

[32]

Solid

Targeted therapy

Cilengitide

Cilengitide

Phase I

OBD

DLT + biological activity rate (BAR)

Consecutive/sequential cohorts

CR (RECIST criteria)

PK/PD

[33]

Solid

Targeted therapy

Celecoxib

Erlotinib

Celecoxib

Phase I

OBD

DLT + urinary PGE-M level

Consecutive/sequential cohorts

CR (RECIST criteria)

[34]

Solid

Targeted therapy

WX-554

WX-554

Phase I

OBD/MTD

DLT + maximal target inhibition

3 + 3

CR (RECIST criteria)

PK/PD

[35]

Solid

Targeted therapy

All-trans-retinoic acid

Tamoxifen

Alpha-interferon 2a

All-trans-retinoic acid (ATRA)

Phase I

OBD

Biological response

Consecutive/sequential cohorts

PK