Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
INO-5401 · 2 trials · 2 indications
An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. TEAEs were defined as any AEs that occurred on or after Day 0. AESIs were toxicities and immune-mediated AEs that may have occurred up to 90 days after the last dose of trial treatment. AESIs were reported by the investigator to the Sponsor within 24 hours after learning of the event.
Clinically significant changes in hematological parameters were determined based on the investigator's discretion.
Clinically significant changes in serum chemistry parameters were determined based on the investigator's discretion.
Clinically significant changes in urinalysis parameters were determined based on the investigator's discretion.
Blood and tissue samples were collected to evaluate the antigen-specific immune response to INO-5401 + INO-9012 in combination with atezolizumab. Planned assessments included: Enzyme Linked Immunosorbent Spot-forming (ELISpot) Assay, Flow cytometry, T cell receptor (TCR) sequencing, ELISA and/or gene expression analysis.
ORR was defined as the percentage of participants who had a confirmed complete response (CR) or a partial response (PR). CR was defined as disappearance of all target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters) per RECIST 1.1.
| Arm | Type | Description |
|---|---|---|
| Cohort A: Prior Anti-PD-1/PD-L1 | EXPERIMENTAL | Participants with locally advanced unresectable or metastatic/recurrent UCa, who had confirmed disease progression during or following treatment with anti- programmed death receptor-1/ programmed cell death-ligand 1 (PD-1/PD-L1) therapy received INO-5401 9 milligrams (mg) and INO-9012 1 mg, intramuscular (IM) injection, followed by electroporation (EP) by CELLECTRA® 2000 device, every 3 weeks until Week 9, then every 6 weeks for 6 more doses (until Week 45), thereafter every 12 weeks, until confirmed disease progression, unacceptable toxicity, or deemed intolerable by the investigator in combination with atezolizumab 1200 mg, intravenous (IV) infusion, every 3 weeks, until confirmed disease progression, unacceptable toxicity, or deemed intolerable by the investigator. |
| Cohort B: Naïve Anti-PD-1/PD-L1 | EXPERIMENTAL | Participants with locally advanced unresectable or metastatic/recurrent UCa who are treatment naïve and ineligible for cisplatin-based chemotherapy received INO-5401 9 mg and INO-9012 1 mg, IM injection, followed by EP by CELLECTRA® 2000 device, every 3 weeks until Week 9, then every 6 weeks for 6 more doses (until Week 45), thereafter every 12 weeks, until confirmed disease progression, unacceptable toxicity, or deemed intolerable by the investigator in combination with atezolizumab 1200 mg, IV infusion, every 3 weeks, until confirmed disease progression, unacceptable toxicity, or deemed intolerable by the investigator. |
| Cohort A: Unmethylated MGMT Promoter | EXPERIMENTAL | Cohort A will include participants with a glioblastoma tumor with an unmethylated MGMT promoter. Participants will receive INO-5401 and INO-9012 and cemiplimab as well as radiation and temozolomide (TMZ; only during radiation therapy), if clinically indicated. |
| Cohort B: Methylated MGMT Promoter | EXPERIMENTAL | Cohort B will include participants with a glioblastoma tumor with a methylated MGMT promoter or with indeterminate MGMT status. Participants will receive INO-5401 and INO-9012 and cemiplimab as well as radiation and temozolomide (TMZ), if clinically indicated. Participants will continue to receive TMZ following radiation therapy, for up to six additional cycles, if clinically indicated. |
| Name | Type | Description |
|---|---|---|
| INO-5401 | BIOLOGICAL | INO-5401: A mixture of 3 synthetic plasmids that target Wilms' tumor gene-1 (WT1) antigen, prostate-specific membrane antigen (PSMA) and human telomerase reverse transcriptase (hTERT) antigen. IM injection |
| INO-9012 | BIOLOGICAL | INO-9012: A synthetic plasmid that expresses human interleukin-12 (IL-12). IM injection. |
| Atezolizumab | DRUG | IV-Infusion. |
| CELLECTRA® 2000 | DEVICE | IM injection. |
| Cemiplimab | BIOLOGICAL | Cemiplimab is an antibody to programmed death-1 (PD-1) protein. Starting on Day 0 cemiplimab will be administered intravenously (IV) every three weeks at a dose of 350 mg per dose in the absence of dose holding, until disease progression as defined by iRANO, unacceptable toxicity, withdrawal of consent, or death. |
| Radiation Therapy | RADIATION | Radiation therapy (RT) will begin no later than 42 days after surgical intervention, and should start approximately 2 weeks after Day 0. RT will be given for three weeks. |
| Temozolomide | DRUG | Temozolomide (TMZ) will be given daily during radiation therapy (RT) at a dose of 75 milligrams per square meter (mg/m\^2). |
Inclusion Criteria: * Sign an Informed Consent Form (ICF); * Have histologically or cytologically documented locally advanced unresectable or metastatic/recurrent urothelial carcinoma (including renal pelvis, ureters, urinary bladder, and urethra); * For Cohort A: Participants who have radiographic...
INO-5401 is an investigational immunotherapy being studied for the treatment of glioblastoma and urothelial carcinoma. It is currently in Phase 1 clinical development for these oncology indications.
INO-5401 targets the tumor-associated antigens hTERT, WT1, and PSMA. It is designed to stimulate an immune response against cancer cells expressing these targets.
INO-5401 is being developed by Inovio Pharmaceuticals, Inc., a biopharmaceutical company traded on the NASDAQ under the ticker symbol INO.
INO-5401 is in Phase 1 clinical development. It is an investigational drug and has not been approved by the FDA for any indication.
INO-5401 has been studied in two Phase 1 trials. NCT03502785 evaluated INO-5401 plus INO-9012 with atezolizumab in urothelial carcinoma and is completed. NCT03491683 is an active, not recruiting trial of INO-5401 and INO-9012 with cemiplimab in newly-diagnosed glioblastoma.
No, INO-5401 and INO-9012 are distinct investigational agents. In clinical trials, they are often administered together as a combination regimen along with checkpoint inhibitors such as atezolizumab or cemiplimab.