Clinical Trials

Human Clinical Trials Summary

Olvi-Vec has been studied in multiple early- and mid-phase clinical trials via regional and systemic deliveries, as a monotherapy and in combination with other therapies, in a total of 148 patients with a variety of cancer types.

 

There are several key documented takeaways from all our trials that apply, irrespective of the route of administration, dosing regimen or cancer type. Olvi-Vec was:

 

  • Observed to be well tolerated. Whether administered in a single dose or multiple doses per cycle, no MTD was reached in any of the trials and there were no significant issues with virus shedding into the environment.
  • Shown to infect and selectively kill tumor cells, initiate an antitumoral response, and modulate the tumor microenvironment, including re-sensitizing certain tumors to chemotherapy.
  • Observed to have a virus-dose dependent benefit on disease control (including tumor growth reduction), progression-free survival (PFS), overall survival (OS) and other clinical benefits in a monotherapy setting.
  • Shown to enhance chemotherapeutic activities in a combination therapy setting.

 

There were also several key documented takeaways from our trials in which Olvi-Vec was systemically administered. Olvi-Vec was shown to::

 

  • Be likely to overcome pre-existing anti-vaccinia antibody levels by high and condensed dosing.
  • Be Detectable in the active state as live virus in blood circulation, even at two hours after infusion, which allows ample time for the virus to reach distal metastases.
  • Potentially infect tumor tissues and reduce circulating tumor cells.

 

The following tables summarize the seven human clinical trials conducted with Olvi-Vec.

Protocol Number

GL- ONC1-002/MA (United Kingdom: Phase 1 – NCT00794131)

Indication

Advanced solid tumors

Modality & Route

Monotherapy as intravenous infusion

Results

  • Well-tolerated and maximum tolerated dose not reached.
  • Multiple high doses of virus delivered by i.v. route:

(A) demonstrated to be feasible:
(i) extended PK (overcoming neutralizing antibodies), (ii) confirmed viral infection, replication at tumor sites distal to site of administration and in circulating tumor cells, (iii) induction of proinflammatory response and triggering activation of adaptive immunity

(B) demonstrated to generate antitumor activity and clinical benefits, including a virus-dose-dependent overall survival benefit, especially in patients with primary lung cancer or other tumor types with lung metastases. Of the 22 evaluable patients with such lung disease, 11 patients who received the lower cumulative dose had a mOS of 4.6 mos vs. a mOS of 16.8 mos for the 11 patients who received the higher cumulative dose (p = 0.026); when further extending the analysis, the five patients who received the lowest cumulative dose had a mOS of 4.6 months vs a mOS of 20,9 mos for the 11 patients who received the highest cumulative dose (p = 0.002).

Protocol Number

GL-ONC1-003/MSK (United States: Phase 1 (Investigator Sponsored) – NCT01766739)

Indication

Malignant pleural effusion related either to malignant pleural mesothelioma

Modality & Route

Monotherapy as intrapleural catheter delivery

Results

  • Well-tolerated, no dose-limiting toxicities, and maximum tolerated dose not reached
  • No virus shedding detected
  • Confirmed viral availability and PK in pleural fluid after multiple high doses of virus delivered by i.v. route:
  • Confirmed viral infection and replication in tumor tissues
  • Confirmed trend of survival advantage for patients with epithelioid subtype of mesothelioma when compared to well-documented historical data.

The median overall survival (mOS) was 22.3 mos vs. historical 14 mos in all epithelioid subtype patients: for those who did not have subsequent surgery, the mOS was 23.4 mos vs. historical 10 mos; and for those who had subsequent surgery, the mOS was 22.3 mos vs. historical 19 mos.

Protocol Number

GL- ONC1-004/TUE (Germany: Phase 1 – NCT01443260)

Indication

Peritoneal carcinomatosis

Modality & Route

Monotherapy as intraperitoneal catheter delivery

Results

  • Well-tolerated, and no dose-limiting toxicities, and maximum tolerated dose not reached
  • Confirmed viral infection and replication in tumor tissues and oncolysis of tumor cells; and induction of proinflammatory response and antitumor immune response
  • Confirmed antitumor activity: Of the 6 patients receiving more than one dose, 67% exhibited SD by RECIST 1.1 (with one exhibiting PR by CHOI criteria).

Protocol Number

GL-ONC1-005/UCSD (United States: Phase 1 – NCT01584284)

Indication

Newly diagnosed head and neck cancer

Modality & Route

Combination therapy with intravenous or bolus injection with cisplatin and radiotherapy

Results

  • Well tolerate and no maximum tolerated dose reached.
  • No virus shedding detected
  • Confirmed (i) viral infection and replication of tumor tissues and (ii) induction of proinflammatory response and T-cell activation pathways
  • Confirmed 90% (17/19) ORR [77% (13/17) with CR], compared to historical of 64% ORR. Favorable PFS and OS as compared to well-documented historical data: The 1-year progression-free survival (PFS) rate was 66%, and 1-year overall survival (OS) rate was 86% in HPV-negative Stage IV patients, relative to historical data, including both Stage III & Stage IV patients, of 1-year PFS at 60%, and 1-year OS at 70%.

Protocol Number

GL- ONC1-011/UCSD (United States: Phase 1 (Investigator Sponsored) – NCT02714374)

Indication

Solid Organ Cancer

Modality & Route

Neoadjuvant monotherapy as intravenous bolus infusion followed by surgical resection of tumor

Results

  • Well tolerated and no dose-limiting toxicities and maximum tolerated dose not reached
  • Confirmed feasibility of systemic route of delivery: (i) live virus detected in blood circulation hours after completion of virus infusion; (ii) viral infection and replication in tumor tissues and (iii) induction of increased tumor-infiltrating lymphocytes into virus-infected tumor tissues

Protocol Number

GL- ONC1-021/AHCI (United States: EAP – NCT03420430)

Indication

Advanced cancers (solid tumors & blood cancer)

Modality & Route

Monotherapy as intravenous bolus infusion

Results

  • Well tolerated and no dose-limiting toxicities and maximum tolerated dose not reached
  • Confirmed objective response and clinical benefit of monotherapy and immunochemotherapy. Clinically-significant antitumor effects were documented in two of three solid tumor patients who received Olvi-Vec-primed immunochemotherapy.

Protocol Number

GL–ONC1-015/AHCI (United States: Phase 1b/2 – NCT02759588)

Indication

Platinum resistant/ refractory ovarian cancer, fallopian cancer or primary peritoneal carcinomatosis

Modality & Route

IP Infusion as Monotherapy or as combination therapy with carboplatin doublet chemotherapy + bevacizumab

Results

  • Primary endpoints met
  • Well tolerated and no dose-limiting toxicities and maximum tolerated dose not reached
  • Confirmed trend of favorable PFS, ORR and OS. The mPFS was 11.0 mos, ORR was 54%, and OS was 15.7 mos as compared to well-documented historical data <4 mos, <20%, < 12 mos, respectively; and as compared to a mPFS of 4.5 mos on the patients’ immediate prior line of therapy (historically, mPFS generally decreases with each subsequent line of therapy.

Exploratory Objectives:

Demonstrated viral infection and replication in tumor tissues, and oncolysis of tumor cells

Demonstrated virus-mediated modulation of tumor immune microenvironment; induction of antitumor immune response

The diverse Olvi-Vec clinical program has yielded data that informs our clinical development strategy and trial design for multiple indications. For more information see corporate deck here.

Expanded Access Policy

Outside of our clinical trials, we may provide physician-requested expanded access to its investigational products under limited situations. The request for access to a Genelux investigational drug will be considered only if all the following criteria are met.

 

  • The patient has a serious or life-threatening disease or condition with no comparable or satisfactory alternative therapies
  • The patient is not eligible for or unable to participate in a clinical trial
  • The investigational drug is currently in clinical development with sufficient evidence of safety and effectiveness for patient’s specific condition
  • A benefit-risk analysis suggests that the benefit from using of the investigational drug outweighs the known or anticipated risks based on evolving clinical data
  • We have adequate supply of investigational drug

 

If the investigational drug is approved by a regulatory agency for commercial use, including provisional approval, existing expanded access programs will be phased out or modified accordingly.

 

Patients interested in seeking an expanded access to a Genelux investigative drug should talk to their physician. All requests must be made by the patient’s treating physician by email at EAP@genelux.com. We will, in general, acknowledge receipt of a request for expanded access within five business days. We may ask for more detailed information to fully evaluate a request.

 

The request for access to an investigative drug can only be considered if the requesting physician agrees to obtain applicable regulatory and ethics committee approvals. We may deny access if the treating physician cannot guarantee an appropriate storage and handling of the investigative drug, which typically requires a temperature controlled deep freezer and follows Biosafety Level 2 safety procedures and precautions. The treating physician must agree to comply with regulatory obligations, including safety monitoring and reporting.

 

For more information on expanded access from the FDA, click here.