Table 2.
Clinical Trials with Replication-Deficient Viruses Encoding p53
| Trial ID | Phase | Cancer | Virus Name | Combination with Treatments/Vaccination | Patients (n) | Mode of Injection | Reported Results | Dose | References |
|---|---|---|---|---|---|---|---|---|---|
| I | lung NSCLC | adenovirus rAd/p53 (SCH58500) | – | 15 | i.t. | no toxicity (safe) transient gene transfer efficacy detection of specific WT p53 sequences local disease control no response at untreated tumor sites 2 patients with SDI 11 patients with PD | 1 × 107 to 1 × 1010 PFU (= 7.5 × 109 to 7.5 × 1012 VP) (dose escalation) | 128 | |
| I | advanced solid cancers | adenovirus Ad-p53 | hyperthermia | 15 | i.t. | no dose-limiting toxicity, safe and efficient four patients with PR two patients with CR eight patients with SDI one patient with PD | 1 × 1012 VP given four to eight times | 173 | |
| I | NSCLC | adenovirus Ad-p53 | – | 28 | i.t. | minimal toxicity presence of vector in 86% of patients apoptosis increased in 11 patients 2 patients with PR 16 patients with SDI 7 patients with PD | 1 × 106 PFU to 1 × 1011 PFU given monthly up to six times | 174 | |
| I/II | metastatic pancreatic cancer | adenovirus SCH58500 | gemcitabine | 3 | intra-arterial | transient toxicity one patient with transient SDI one patient with reduction of tumor burden | 2.5 × 1012 VP (four times), or 2.5 × 1012 VP (two times), or 7.5 × 1012 VP (one time) | 129 | |
| I | colorectal | adenovirus SCH58500 | – | 45 | hepatic arterial infusion | limited and transient inflammatory responses increase of total and neutralizing Ab virus delivery in tumor and liver apoptosis detected in tumor with an elevated nuclear expression of p53 | 7.5 × 109 to 7.5 × 1013 VP for single dose or 7.5 × 1011 to 2.5 × 1013 VP for multiples doses | 130 | |
| I | NSCLC | adenovirus Ad-p53 | cisplatin | 24 | i.t. | mild toxicity transgene expression detected in tumor apoptosis increased in 11 patients 2 patients with PR 17 patients with SDI 4 patients with PD | 1 × 106 to 1 × 1011 VP (dose escalation) | 175 | |
| I | glioma | adenovirus Ad-p53 (INGN 201) | – | 15 | i.t. | minimum of toxicity exogenous p53 detection in tumor cells in all patients apoptosis triggering lack of viral widespread no determination of response to Ad-p53 | 3 × 1010 to 3 × 1012 VP (dose escalation) | 131 | |
| II | squamous cell carcinoma of the oral cavity | adenovirus Ad5CMV-p53 (INGN 201) | cisplatin + radiotherapy | 13 | i.t. | excellent 1-year progression-free survival rate (92%) | 2.5 × 1012 VP (three times) | 132 | |
| II | breast cancer | adenovirus Ad5CMV-p53 | docetaxel and doxorubicin | 13 | i.t. | no systemic toxicity (safe) no CR increase in p53 mRNA local immunomodulator effects | 2.5 × 1012 VP (two times/cycle during six cycles) | 176 | |
| I | HNSCC | adenovirus Ad-p53 | – | 33 | i.t. | no toxicity p53 expression detected two patients with tumor regression six patients with SDI one patient with CR nine patients with PD | 1 × 106 to 1 × 1011 PFU (dose escalation) 3 × 1012 PFU/patients (total dose) | 177 | |
| I | bladder | adenovirus SCH58500 (rAd/p53) | – | 12 | i.t., intravesicular instillation | mild toxicity (safe) p53 transgene detection in tumor cells high transduction of adenovirus in tumor by intravesical instillation | 7.5 × 1011 to 7.5 × 1013 VP (one dose) | 133 | |
| I/II | ovarian | adenovirus rAd-p53 (SCH58500) | – | 41 | i.p. | no toxicity (safe) no severe side effects increase of serum adenoviral antibody titers effects virus tolerated detection of p53 transgene | 7.5 × 1010 to 7.5 × 1013 VP (single or multiple doses) | 134 | |
| II | NSCLC | adenovirus rAd/p53 (SCH58500) | chemotherapy (carboplatin + paclitaxel or cisplatin + vinorelbine) | 25 | i.t. | mild toxicity transgene detection in tumor no benefit of p53 viral therapy on lesions no benefit concerning the survival of patients | 7.5 × 1012 VP/cycle during three cycles | 135 | |
| II | lung | adenovirus Ad-p53 (INGN 201) | radiation | 19 | i.t. | tolerated treatment tumor regression at the primary injected tumor increase of BAK gene expression 1 patient with CR 11 patients with PR 3 patients with SDI 2 patients with PD | 3 × 1011 to 3 × 1012 VP (three times) | 136 | |
| I | lung | adenovirus Ad-p53 | – | 25 | bronchoalveolar lavage (BAL) | safe low side effects for 5 × 1011 VP 16 patients with SDI | 2 × 109 to 2 × 1012 VP (dose escalation) | 138 | |
| I | NSCLC | retrovirus having p53 transgene (ITRp53A) | – | 9 | i.t. | no toxic effects increase of apoptosis detection of vector p53 sequence | 5 × 107 CFU (single or multiple cycles) | 47 | |
| I/II | metastatic malignant liver tumors | adenovirus CMV-p53 | – | 19 | hepatic artery infusion | ND | 1 × 109 to 3 × 1011 PFU (dose escalation) | 178 | |
| I | ovarian | adenovirus Adp53 (INGN 201) | – | 17 | i.p. | no severe toxicities effects virus tolerated (no dose limited toxicities) four patients with DS five patients with PD | 3 × 1010 to 3 × 1012 VP (daily for 5 days every 3 weeks) | 137 | |
| – | NSCLC | adenovirus rAd-p53 | bronchial arterial infusion (BAI) | 58 | i.t. or bronchial arterial access | virus tolerated delay of the disease progression increase patient life quality no benefit on patient survival | 1 × 1012 to 4 × 1012 VP (four times) | 179 | |
| I | SCLC | adenovirus Ad-p53 | vaccination with dendritic cells infected by Ad-p53 | 29 | intradermal | 57.1% of patients present a p53-specific T cell response slight increase of anti-adenovirus antibodies better response to chemotherapy after vaccination one patient showed a clinical response to vaccination | ND | 139 | |
| NCT01191684 | I | refractory gastrointestinal cancers | poxvirus Modified Ankara virus (p53MVA) | vaccination | 12 | subcutaneous | virus tolerated no severe adverse events strong CD8+ T cell response against cancer cells expressing p53 | 1 × 108 to 5.6 × 108 PFU (dose escalation) | 147 |
| NCT00003147 | I | hepatocellular carcinoma | Ad5CMV-p53 | – | – | percutaneous injection | – | ND | |
| NCT02418988 | II | hepatocellular carcinoma | rAd-p53 | TACE (transarterial chemoembolization) | – | arterial injection | recruiting | ND | |
| NCT00902083 | IV | oral and maxillofacial tumors | rAd-p53 | chemotherapy/surgery | – | i.t. | – | 1 × 1012 VP | |
| NCT00902122 | IV | thyroid | rAd-p53 | radioactive iodine/ surgery | – | i.t. | – | 1 × 1012 VP | |
| NCT02429037 | II | head and neck | rAd-p53 | radio-chemotherapy (cisplatin/paclitaxel) | – | i.t. | – | 2 × 1012 VP | |
| NCT02429726 | II | malignant pleural effusion | rAd-p53 | cisplatin | – | intra-chest cavity infusion | – | 2 × 1012 VP | |
| NCT02275039 | I | recurrent ovarian cancer | poxvirus Modified Ankara virus (p53MVA) | vaccination + gemcitabine | – | subcutaneous | ongoing | ND | |
| NCT02432963 | I | solid tumors | poxvirus Modified Ankara virus (p53MVA) | vaccination + pembrolizumab | – | subcutaneous | ongoing | ND | |
| NCT00776295 | II | SCLC | adenovirus Ad-p53 | vaccination with dendritic cells infected by Ad-p53 and T lymphocytes | – | unknown | – | ND | |
| NCT00049218 | I/II | SCLC | adenovirus Ad-p53 | vaccination with dendritic cells infected by Ad-p53+ carboplatin or etoposide | – | subcutaneous | – | ND |
CR, complete response; i.p., intraperitoneal; i.t., intratumoral; mRNA, messenger RNA; NSCLC, non-small cell lung cancer; PD, progressive disease; PR, partial response; SCLC, small cell lung cancer; SDI, stable disease.