Neoplasms

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Gland and Hormone Related Diseases

All Conditions

Infections

Rare Diseases

Pancreatic Neoplasms

Virus Diseases

Adenoviridae Infections

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Atezolizumab

Immunoglobulins

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Patients will receive gemcitabine intravenously at a dose of 1000mg/m2 + nab-paclitaxel 125 mg/m2 as per hospital standards. One cycle will be one dose of gemcitabine +nab-paclitaxel given on days 1, 8, and 15 of a 28 day cycle. LOAd703 will be given every other week for 6 doses starting on day 15 of the first cycle of chemotherapy. There is an option for an additional 6 doses if patients benefit from treatment.

The following LOAd703 doses will be evaluated:

Dose level 1: 5 X 10\^10 viral particles per treatment Dose level 2: 1 X 10\^11 viral particles per treatment Dose level 3: 5 X 10\^11 viral particles per treatment

Patients will receive gemcitabine intravenously at a dose of 1000mg/m2 + nab-paclitaxel 125 mg/m2 as per hospital standards. One cycle will be one dose of gemcitabine +nab-paclitaxel given on days 1, 8, and 15 of a 28 day cycle. LOAd703 will be given every other week for 6 doses starting on day 15 of the first cycle of chemotherapy. There is an option for an additional 6 doses if patients benefit from treatment. A fixed dose of atezolizumab 1680 mg will be given every 4 weeks on day 1 of each chemotherapy cycle.

Patients will be assigned to the following LOAd703 doses:

Dose level 1: 1 X 10\^11 viral particles per treatment Dose level 2: 5 X 10\^11 viral particles per treatment

oncolytic virus encoding TMZ-CD40L and 4-1BBL

delolimogene mupadenorepvec

gemcitabine

nab-paclitaxel

atezolizumab

Benjamin Musher, MD

Monica Francois

Angelica Loskog, PhD

The purpose of this study is to see if LOAd703 (an oncolytic adenovirus) can be safely given to patients with pancreatic cancer. The study will also evaluate whether or not intratumoral injection of LOAd703 will support current standard of care treatment to reduce the size of the tumor and improve survival of the patients.

Adenoviruses are known as the "common cold" virus and most individuals have had multiple infections during their lifetime. Oncolytic adenoviruses are adenoviruses that are modified so they cannot multiply and spread (known as replicating) properly in normal (e.g. healthy) cells, but instead, they infect and replicate very well in cancer cells. This strong replication leads to the death of the cancer cell. Oncolytic viruses have been evaluated in multiple clinical trials for cancer treatment during the past decade and been proven safe. It is common to have a fever the first day or two after virus injection since the immune system will react to the virus infection. The immune system can also kill cancer cells but to do so it needs to be properly stimulated. Oncolytic viruses alone do not seem to be strong enough to activate clinically relevant anti-cancer responses. However, it is thought that if additional immune system stimulators are added to the oncolytic viruses they may be able to result in clinical relevant antic-cancer responses.

LOAd703 is an oncolytic adenovirus that has been modified to include additional immune system stimulators. Specifically, genes that stimulate the immune system have been added to the oncolytic adenovirus. Once the oncolytic adenovirus infects the cancer cells, the genes will be expressed, resulting in activation of the immune response so it can attack and kill cancer cells.

In this study, LOAd703 will be given by intratumoral injections. It will be given in addition to standard of care treatment with gemcitabine and nab-paclitaxel +/- the anti-PD-L1 antibody atezolizumab. Because this is an experimental therapy, there will be extra visits for disease monitoring and samples accordingly to the detailed information below. The LOAd703 is an investigational agent not approved by the FDA.

The research will be conducted at Baylor College of Medicine (BCM) and Baylor St. Luke's Medical Center (BSLMC).

All patients will receive standard of care treatment for their pancreatic cancer. Standard of care treatment will be gemcitabine in combination with nab-paclitaxel given on days 1, 8, and 15 of a 28 day cycle.

Arm 1: LOAd703 treatment will be initiated at day 15 of the first cycle and given every other week for 6 doses. Depending on the location of the tumor the injection of LOAd703 can be given in different ways. The most common route of injection is ultrasound-guided percutaneous injection, but endoscopic ultrasound-guidance will be used for some patients as appropriate. All patients will receive anti-anxiety drugs or sedation as needed for comfort during the procedure. This study evaluates different doses of LOAd703. All patients will receive six injections of LOAd703. If patients in either phase of the study are judged by the investigator to be deriving clinical benefit from LOAd703 once all scheduled injections have been administered, they will be eligible to receive up to 6 additional biweekly doses of LOAd703.

Arm 2: the same procedures as arm 1 in regard to LOAd703. In addition, the arm 2 patients will receive atezolizumab at a fixed dose, every chemotherapy cycle day 1. The treatments can continue until the final follow-up visit.

Follow-up visits: Besides visits to receive treatments, patients will continue to visit BCM/BSLMC or their local doctor for evaluation of health status and side effects. At some visits blood samples will be obtained. Some of the blood samples being obtained are considered standard of care to ensure patient safety for standard of care treatment and the LOAd703 injection. However, some blood and biopsy samples (in applicable patients) will be collected to be analyzed for the presence of LOAd703, atezolizumab tumor markers and immunology markers. The extra blood will be 5-15 ml (3 teaspoonfuls) of blood collected at the screening visit and at eight different time points both during treatment and after treatments are completed. Imaging of the tumor to determine tumor size will be done every two to three months, which is routine for the monitoring of patients with pancreatic cancer. Patients will actively participate in the study for about 9 months when the final follow-up visit will be scheduled (or 12 months if additional doses of LOAD703 are given). After their active participation is completed patients will continue to receive routine care and will be contacted by the study team every 3 months to provide follow up on the status of their disease.

LOAd703 Oncolytic Virus Therapy for Pancreatic Cancer

Phase I/IIa Trial Evaluating Safety of LOAd703, an Armed Oncolytic Adenovirus for Pancreatic Cancer

Maximum tolerated dose of multiple (6x) image-guided intratumoral injections of LOAd703 at three dose levels in combination with standard of care therapy

To determine the percentage of subjects achieving a partial response or better (according to RECIST 1.1) to repeat doses of LOAd703 (at the highest dose as determined in Phase I) combined with standard of care treatment with and without atezolizumab in pancreatic cancer.

To determine the survival days post study initiation

Lokon Pharma AB

Colorectal Neoplasms

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Bevacizumab

Immunomodulating Agents

Angiogenesis Inhibitors

Growth Inhibitors

Participants will receive treatment until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.

Participants will receive treatment until unacceptable toxicity or loss of clinical benefit as confirmed by disease progression per RECIST V1.1 or lack of continued benefit as determined by the investigator.

Regorafenib will be administered orally on Days 1-21 of each 28-day cycle.

Regorafenib

Atezolizumab will be administered by intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of 21-day cycles, with the exception of the Atezolizumab + Selicrelumab + Bevacizumab, Atezolizumab + Idasanutlin, Atezolizumab + Regorafenib and Atezolizumab + Regorafenib + AB928 arms where the Atezolizumab will be administered by IV infusion every 2 weeks (Q2W) on Days 1 and 15 of each 28-day cycle.

Imprime PGG will be administered by IV infusion weekly on Days 1, 8, and 15 of each 21-day cycle.

Imprime PGG

Bevacizumab will be administered by IV infusion on Day 1 of each 21-day cycle for the Atezolizumab + Imprime PGG + Bevacizumab arm, and on Day 1 and Day 15 of each 28-day cycle for the Atezolizumab + Selicrelumab + Bevacizumab arm.

Isatuximab will be administered on Day 1, 8 and 15 of cycle 1 and on day 1 of all subsequent cycles. Cycles will be 21 days long.

Isatuximab

Selicrelumab will be administered by subcutaneous (SC) injection on Day 1 of cycles 1-4 and every third cycle thereafter. Cycles will be 28 days long.

Selicrelumab

Idasanutlin will be administered orally on Days 1-5 of each 28-day cycle.

Idasanutlin

AB928 will be administered orally once daily on Days 1-28 of each 28-day cycle.

AB928

LOAd703 will be administered by intratumoral injection on Day 1 of each 21-day cycle.

LOAd703

Clinical Trials

A phase Ib/II, open-label, multicenter, randomized study designed to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of immunotherapy-based treatment combinations in patients with metastatic colorectal cancer (mCRC) that became refractory to first- and second-line standard therapies. Eligible patients will be assigned to one of several treatment arms.

A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic Colorectal Cancer (Morpheus-CRC)

A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic Colorectal Cancer (Morpheus-CRC)

The best confirmed overall response rate (ORR) is defined as the percentage of participants with a complete response or partial response on two consecutive occasions ≥4 weeks apart, as determined by the investigator according to RECIST v1.1. Participants could be classified as "Stable Disease" if the assessment was at least 6 weeks from randomization. Participants were classified as Missing if no post-baseline response assessments were available. Participants were classified as Not Evaluable if all post-baseline response assessments were unevaluable. The differences in ORR between the experimental arms and the corresponding control arm were calculated, along with 95% confidence intervals (CIs), using normal approximation of the binomial distribution. The 95% CIs for ORRs were constructed using the Clopper-Pearson method. The 95% CIs for the difference in rates were constructed using the Wald method with continuity correction.

Progression-free survival (PFS) after randomization, defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), was determined by the investigator according to RECIST v1.1. For participants who did not have documented disease progression or death, PFS was censored at the day of the last tumor assessment. The Kaplan-Meier method was used to estimate the median for PFS with 95% confidence intervals (CIs) constructed through use of the Brookmeyer and Crowley method.

Overall survival (OS) is defined as the time from randomization to death from any cause. Participants who were still alive at the time of OS analysis were censored at the last date they were known to be alive. The Kaplan-Meier method was used to estimate the median for OS with 95% confidence intervals (CIs) constructed through use of the Brookmeyer and Crowley method.

Overall survival (OS) is defined as the time from randomization to death from any cause. Participants who were still alive at the time of OS analysis were censored at the last date they were known to be alive. OS is shown as the percentage of participants who were event-free at the landmark timepoints of 3, 6, 12, and 18 months.

Duration of response is defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause.

Disease control rate is defined as the percentage of participants with stable disease for ≥12 weeks or a complete or partial response, as determined by the investigator according to RECIST v1.1.

The incidence, nature, and severity of adverse events (AEs) are reported, with severity determined according to NCI CTCAE v4.0. All AEs were reported until 30 days after the last study dose or until start of new systemic anti-cancer therapy. Serious AEs and AEs of special interest were reported until 135 days (or 180 days for the Atezolizumab + LOAd703 arm only) after the last dose of study treatment.

Hoffmann-La Roche

All-Cause Mortality is reported in the all-enrolled patients population. Adverse events (AEs) are reported in the safety population, defined as all those who received ≥1 dose of study treatment. One participant in the Regorafenib arm died before receiving study dose. All AEs were reported until 30 days after the last study dose or until the start of new systemic anti-cancer therapy. Serious AEs and AEs of special interest are reported until up to 180 days after last study dose.

Regorafenib (Control)

Atezolizumab + Imprime PGG + Bevacizumab

Atezolizumab + Isatuximab

Atezolizumab + Selicrelumab + Bevacizumab

Atezolizumab + Idasanutlin

Atezolizumab + Regorafenib

Atezolizumab + Regorafenib + AB928

Atezolizumab + LOAd703

Total

Age (year)

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

ECOG performance status scale. 0 - Fully active; able to carry on all predisease performance without restriction

1 - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature

ECOG score

Number of Metastatic Sites at Enrollment

All participants who were randomized in the study, regardless of whether they actually received any study treatment.

This study is not designed to make explicit power and Type I error considerations for a hypothesis test. Instead, this study is designed to obtain preliminary efficacy, safety, and PK data. No formal statistical hypothesis testing was performed in this study. Due to the limited sample size, the results need to be interpreted with caution. For the Atezo+Idasa and Atezo+LOAd703 groups, no meaningful conclusion could be drawn because these experimental arms have been terminated prematurely.

Medical Communications

Responders (CR + PR)

Complete Response (CR)

Partial Response (PR)

Stable Disease (SD)

Progressive Disease (PD)

Not Evaluable

Missing

The efficacy evaluable population included all patients who received at least one dose of each drug for their assigned treatment regimen.

Best Confirmed Overall Response Rate (ORR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Progression-Free Survival (PFS) as Determined by Investigator According to RECIST v1.1

Atezolizumab + Imprime PGG + Bevacizumab vs. Regorafenib (Control) Hazard Ratio for OS

Atezolizumab + Isatuximab vs. Regorafenib (Control) Hazard Ratio for OS

Atezolizumab + Selicrelumab + Bevacizumab vs. Regorafenib (Control) Hazard Ratio for OS

Atezolizumab + Idasanutlin vs. Regorafenib (Control) Hazard Ratio for OS

Atezolizumab + Regorafenib vs. Regorafenib (Control) Hazard Ratio for OS

Atezolizumab + Regorafenib + AB928 vs. Regorafenib (Control) Hazard Ratio for OS

Atezolizumab + LOAd703 vs. Regorafenib (Control) Hazard Ratio for OS

The efficacy evaluable population included all participants who received at least one dose of each study drug for their assigned treatment regimen.

Overall Survival (OS)

Difference in OS event-free rate at 3 months for the Atezolizumab + Imprime PGG + Bevacizumab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 6 months for the Atezolizumab + Imprime PGG + Bevacizumab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 12 months for the Atezolizumab + Imprime PGG + Bevacizumab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 18 months for the Atezolizumab + Imprime PGG + Bevacizumab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 3 months for the Atezolizumab + Isatuximab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 6 months for the Atezolizumab + Isatuximab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 12 months for the Atezolizumab + Isatuximab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 18 months for the Atezolizumab + Isatuximab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 3 months for the Atezolizumab + Selicrelumab + Bevacizumab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 6 months for the Atezolizumab + Selicrelumab + Bevacizumab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 12 months for the Atezolizumab + Selicrelumab + Bevacizumab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 18 months for the Atezolizumab + Selicrelumab + Bevacizumab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 3 months for the Atezolizumab + Idasanutlin vs. Regorafenib (Control) arms

Difference in OS event-free rate at 6 months for the Atezolizumab + Idasanutlin vs. Regorafenib (Control) arms

Difference in OS event-free rate at 12 months for the Atezolizumab + Idasanutlin vs. Regorafenib (Control) arms

Difference in OS event-free rate at 18 months for the Atezolizumab + Idasanutlin vs. Regorafenib (Control) arms

Difference in OS event-free rate at 3 months for the Atezolizumab + Regorafenib vs. Regorafenib (Control) arms

Difference in OS event-free rate at 6 months for the Atezolizumab + Regorafenib vs. Regorafenib (Control) arms

Difference in OS event-free rate at 12 months for the Atezolizumab + Regorafenib vs. Regorafenib (Control) arms

Difference in OS event-free rate at 18 months for the Atezolizumab + Regorafenib vs. Regorafenib (Control) arms

Difference in OS event-free rate at 3 months for the Atezolizumab + Regorafenib + AB928 vs. Regorafenib (Control) arms

Difference in OS event-free rate at 6 months for the Atezolizumab + Regorafenib + AB928 vs. Regorafenib (Control) arms

Difference in OS event-free rate at 12 months for the Atezolizumab + Regorafenib + AB928 vs. Regorafenib (Control) arms

Difference in OS event-free rate at 18 months for the Atezolizumab + Regorafenib + AB928 vs. Regorafenib (Control) arms

Difference in OS event-free rate at 3 months for the Atezolizumab +LOAd703 vs. Regorafenib (Control) arms

3 Months

6 Months

12 Months

18 Months

The efficacy evaluable population included all participants who received at least one dose of each study drug for their assigned treatment regimen. The number analyzed at each landmark timepoint indicates the number of participants who were remaining at risk for an event. The event-free rate was not estimable (NE) for landmark timepoints at which 0 participants were remaining at risk for an an event.

Percentage of Participants Who Were Alive at Landmark Timepoints for Overall Survival (OS)

The duration of response analysis included all participants from the efficacy evaluable population who had a confirmed overall response; only 1 participant in each of the atezolizumab + regorafenib arm and the atezolizumab + regorafenib + AB928 arm had a confirmed response.

Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1

Disease Control Rate (DCR), as Determined by the Investigator Per RECIST v1.1

Adverse Event (AE)

Death

Withdrawn from Stage due to an AE

AE with a Fatal Outcome

Serious AE (SAE)

SAE Leading to Withdrawal from any Treatment

SAE Leading to Dose Modification/Interruption

Related SAE

AE Leading to Withdrawal from any Treatment

AE Leading to Dose Modification/Interruption

Related AE

Related AE Leading to Withdrawal from any Treatment

Related AE Leading to Dose Modification/Interruption

Grade 3-5 AE

Worst Grade AE: 5

Worst Grade AE: 4

Worst Grade AE: 3

The safety-evaluable population included all patients who received any amount of dose of any component of study treatment.

Percentage of Participants With at Least One Adverse Event (AE)

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Adenocarcinoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Ovarian Cancer

Ovarian Epithelial Cancer

LOAd703 oncolytic adenovirus administered add-on to standard of care chemotherapy or gemcitabine immune-conditioning if standard of care is no longer an option (e.g. after last line)

Oncolytic adenovirus serotype 5/35 encoding TMZ-CD40L and 4-1BBL

This Phase I/II trial evaluates LOAd703 in patients with cancer (pancreatic, biliary, colorectal or ovarian) together with their standard of care chemotherapy or using gemcitabine immune-conditioning. LOAd703 is administered by intratumoral image-guided injections. Maximum 50 patients can be enrolled.

LOAd703 is an immunostimulatory gene therapy using an selection replication competent adenovirus as a gene vehicle. The virus is derived from serotype 5 adenovirus with the fiber from serotype 35. It expresses the transgenes trimerized membrane-bound isoleucine zipper (TMZ) TMZ-CD40L and 41BBL under control of a cytomegalovirus (CMV) promoter.

The trial is a Phase I/II trial evaluating the effect of LOAd703 in patients with pancreatic cancer, biliary cancer, ovarian cancer and colorectal cancer. LOAd703 is an oncolytic adenovirus serotype 5/35 encoding immunostimulatory transgenes: TMZ-CD40L and 41BBL. In Phase I, three doses (total viral load - 1x10e11, 5x10e11, 1x10e12 viral particles (VP)) of LOAd703 will be tested as add-on to standard of care or immune-conditioning gemcitabine chemotherapy. 8 treatments of LOAd703 will be delivered by image-guided intratumoral injection at the same time of chemotherapy. In Phase II stage of the study, patients will be treated at maximum tolerated dose/maximum tolerated study dose as defined in the Phase I stage. In both phases: tumor biopsies, blood samples and radiological imaging will be performed to evaluate safety, effect and mechanisms of action. Further, patients will be subjected to oral and rectal swabs, and urine sampling to determine virus shedding. The patients will be monitored for time to progression, progression free survival and overall survival.

Trial Investigating an Immunostimulatory Oncolytic Adenovirus for Cancer

Phase I/II Trial Investigating an Immunostimulatory Oncolytic Adenovirus for Cancer

Toxicity symptoms graded according to CTCAE v4.x.

Immune reactions to LOAd703 virus as assessed by anti-adenovirus Ig ELISA

Local and distant anti-tumoral size changes assessed by appropriate imaging accordingly to RECIST 1.1

Months of progression free survival from registration

Cytokine relative increase in blood evaluated by cytokine array

Upregulation of activation marker compared to baseline (fold change) evaluated by flow cytometry

LOAd703 virus particles (vp) detected in blood (VP/ml) investigated by quantitative PCR at several time points before and after LOAd703 virus treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
LOAd703 Oncolytic Virus Therapy for Pancreatic Cancer	NCT02705196	Pancreatic Canc...	delolimogene mu... gemcitabine nab-paclitaxel atezolizumab	18 Years -	Lokon Pharma AB
A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic Colorectal Cancer (Morpheus-CRC)	NCT03555149	Colorectal Canc...	Regorafenib Atezolizumab Imprime PGG Bevacizumab Isatuximab Selicrelumab Idasanutlin AB928 LOAd703	18 Years -	Hoffmann-La Roche
LOAd703 Oncolytic Virus Therapy for Pancreatic Cancer	NCT02705196	Pancreatic Canc...	delolimogene mu... gemcitabine nab-paclitaxel atezolizumab	18 Years -	Lokon Pharma AB
A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic Colorectal Cancer (Morpheus-CRC)	NCT03555149	Colorectal Canc...	Regorafenib Atezolizumab Imprime PGG Bevacizumab Isatuximab Selicrelumab Idasanutlin AB928 LOAd703	18 Years -	Hoffmann-La Roche
Trial Investigating an Immunostimulatory Oncolytic Adenovirus for Cancer	NCT03225989	Pancreatic Aden... Ovarian Cancer Biliary Carcino... Colorectal Canc...	LOAd703	18 Years -	Lokon Pharma AB
Trial Investigating an Immunostimulatory Oncolytic Adenovirus for Cancer	NCT03225989	Pancreatic Aden... Ovarian Cancer Biliary Carcino... Colorectal Canc...	LOAd703	18 Years -	Lokon Pharma AB

Spots Global Cancer Trial Database for load703

Every month we try and update this database with for load703 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for load703

Every month we try and update this database with for load703 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for load703 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.