Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

All Drugs and Chemicals

Anti-Infective Agents

Immunomodulating Agents

Valacyclovir

Antiviral Agents

CAN-2409 will be administered intratumorally followed by oral valacyclovir. Valacyclovir will be administered orally at a fixed dose for 14 days after each injection.

CAN-2409 + valacyclovir

This is a phase I dose escalation study of CAN-2409 plus prodrug in patients with non-small cell lung cancer (NSCLC). The primary clinical objective of the study is to evaluate the safety of CAN-2409 plus prodrug when combined with standard surgery for NSCLC. The primary scientific objective is to determine the immunologic changes induced by CAN-2409 plus prodrug.

The purpose of this open-label, dose escalation clinical trial is to investigate the safety of CAN-2409 (aglatimagene besadenovec) plus prodrug prior to surgery in patients with NSCLC. CAN-2409 is a viral immunotherapy approach which utilizes intratumoral administration to selectively induce tumor cell death and elicit both an innate and an adaptive systemic anti-tumor immune response against the injected tumor and uninjected metastases. Local delivery enables these effects while aiming to minimize systemic toxicity. Standard of care surgical resection will be performed about 3 weeks after the CAN-2409 injection. Chemotherapy and/or radiation may begin 6-8 weeks after resection surgery. Choice of chemotherapy depends on the treating oncologist. CAN-2409 (aglatimagene besadenovec) was previously known as AdV-tk, and the combination of CAN-2409 plus prodrug was previously known as GMCI.

Intratumoral Gene Mediated Cytotoxic Immunotherapy in Patients With Resectable Non-Small Cell Lung Cancer

Intratumoral Gene Mediated Cytotoxic Immunotherapy (GMCI) For Resectable Non-Small Cell Lung Cancer

University of Pennsylvania

Candel Therapeutics, Inc.

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

Immune Checkpoint Inhibitors

Acyclovir

Cohort 1A and 1B - persistent but stable disease at least 18 weeks after starting ICI treatment

Cohort 2A and 2B - radiographic progressive disease at least 18 weeks after starting ICI treatment

Cohort 3 - refractory disease defined as progressed by imaging at least 9 weeks after starting ICI treatment (CLOSED TO ENROLLMENT)

Two courses (Cohort 1A and Cohort 2A) or three courses (Cohort 1B and Cohort 2B) of CAN-2409 injection into an accessible involved tumor site followed by 14 days of prodrug (valacyclovir or acyclovir). For Cohort 1B, the third course is optional. All patients will continue standard of care immune checkpoint inhibitor with or without chemotherapy.

Aglatimagene besadenovec

The purpose of this clinical trial is to evaluate the effects of adding CAN-2409 + prodrug for stage III/IV NSCLC patients who are on standard of care first line immune checkpoint inhibitor (ICI) treatment with evidence that the clinical response is inadequate. CAN-2409 is a viral immunotherapy approach that induces tumor-infiltrating T-cells and a consequent PD-L1 up-regulation. A combination of CAN-2409 added to standard of care (SOC) checkpoint inhibitors may lead to improved long-term outcomes for patients with NSCLC who have suboptimal response to ICI therapy.

This clinical trial evaluates the addition of CAN-2409 plus prodrug for stage III/IV NSCLC patients who are on standard of care first line ICI (anti-PD-1/PD-L1) but with evidence of suboptimal response (either disease progression or stable disease at time of study enrollment). CAN-2409 plus prodrug has been shown to increase the response rate to ICI in animal studies. Safety and tolerability of CAN-2409 plus prodrug has been demonstrated in clinical trials in over 950 patients with cancer, including cancers of the lung, pancreas, prostate, and brain. Initial proof of mechanism has been shown in non-small lung cancer, prostate cancer, high-grade glioma, and pancreatic cancer. The eligibility criterion in the current clinical trial is based on time on ICI and response status with cohorts as follows:

Cohort 1A and 1B: patients with stable disease radiographically at least 18 weeks after starting ICI treatment and who are clinically stable

Cohort 2A and 2B: patients with evidence of radiographic progression at least 18 weeks after starting ICI treatment but who are clinically stable.

Cohort 3, which is now closed for enrollment, was for patients who had evidence of radiographic progression at least 9 weeks after starting ICI but who were clinically stable.

The specific ICI treatment regimen is not specified to allow for different standard of care options with or without chemotherapy; for example, pembrolizumab alone, pembrolizumab plus chemotherapy, or atezolizumab/chemotherapy. In addition, it allows stage III patients after chemoradiation who may be on durvalumab as their standard of care. For example, a stage III patient may be eligible for cohort 2 if they have radiographic progression but are clinically stable 18 weeks after starting durvalumab.

The release of Version 05 of the protocol increased enrollment numbers into Cohorts 1 and 2 (from target n=32 evaluable to n=40 evaluable), while closing Cohort 3. In Amendment 6, cohort 1B and 2B were initiated to evaluate a 3-dose regimen of CAN-2409 + prodrug. Adjustments to the sample size extended the anticipated primary completion date for this trial.

The study is a phase II prospective study to evaluate the safety and potential efficacy of CAN-2409 plus prodrug added to standard of care immune checkpoint inhibitor (ICI) therapy in stage III/IV NSCLC

CAN-2409 Plus Prodrug With Standard of Care Immune Checkpoint Inhibitor for Stage III/IV NSCLC

CAN-2409 Plus Prodrug With Standard of Care Immune Checkpoint Inhibitor for Stage III/IV NSCLC Patients

Tumor response as measured by RECIST criteria including overall response rate (ORR) and/or disease control rate (DCR)

Blood and tumor will be evaluated for changes in immune response before and after CAN-2409 + prodrug

Defined as time from date of first dose of CAN-2409 to death by any cause (OS-1). An additional OS will be defined as time from ICI treatment initiation to death due to any cause (OS-2).

Defined as time from date of first dose of CAN-2409 to post-treatment progression or death by any cause (PFS-1). An additional PFS estimate will be calculated from ICI treatment initiation (PFS-2).

Non-small Cell Lung Cancer Symptoms Assessment Questionnaire (NSCLC-SAQ) score after compared to before treatment. The lowest score possible is 0, and the highest score possible is 20. Higher score indicates more severe symptoms.

Tumor Response as measured by iRECIST criteria

NYU Langone Health

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gemcitabine

Fluorouracil

Capecitabine

CAN-2409 + prodrug (valacylovir or acyclovir) in combination with neoadjuvant chemoradiation or SBRT + Surgery

Neoadjuvant chemoradiation or SBRT + Surgery

Three courses of CAN-2409 + prodrug (valacylovir or acyclovir) will be delivered and timed with different phases of therapy: 1) after induction chemotherapy 2) during CR or post-SBRT, and 3) at time of surgery. Up to 2 additional courses of CAN-2409 + prodrug, if feasible, for subjects with disease progression or metastases.

CR will start not more than 2 months after completion of induction chemotherapy. The chemotherapy component of CR may be selected as per institutional standard of care (SOC) and protocols for administration, and may include capecitabine, 5-FU, or gemcitabine. Radiation should consist of a total dose of 45-54 Gy in 1.8-2.0 Gy fractions concurrent with chemotherapy over 3-5.5 weeks.

Chemoradiation

SBRT should start no more than 2 months after completion of induction chemotherapy. For SBRT, the radiation should consist of a total dose of 25-50 Gy in divided fractions over 1-2 weeks.

Stereotactic body radiation therapy

Surgical resection should be performed within 8 weeks after completing CR or SBRT.

Surgery

The purpose of this study is to characterize the safety, preliminary efficacy, and immune biologic activity of CAN-2409 + prodrug (valacyclovir or acyclovir) in subjects with borderline resectable pancreatic cancer who are being treated with neoadjuvant chemoradiation (CR) or stereotactic body radiation therapy (SBRT). The Standard of Care (SOC) Control arm will be used as a benchmark for informal comparisons of efficacy, safety, and biomarkers.

Study design is an open-label Phase 2 trial that randomizes subjects with borderline resectable pancreatic adenocarcinoma to received SOC with (Test arm) or without (Control arm) the addition of CAN-2409 + prodrug (2:1 randomization, Test: Control), beginning after completion of at least 4 months (8 cycles) of a FOLFIRINOX based induction therapy. Confirmation of borderline resectable status will be based on central radiologic review following completion of FOLFIRINOX based induction regimen. Upon enrollment, eligible subjects will receive three courses of CAN-2409 + prodrug, the first course starting prior to CR or SBRT, the second course concurrent with CR or just following completion of SBRT, and the third at time of resection. Up to 2 additional courses are allowed at the time of disease recurrence.

Neoadjuvant CAN-2409 in Combination With Chemoradiation or SBRT for Borderline Resectable Pancreatic Adenocarcinoma

Neoadjuvant CAN-2409 Plus Prodrug in Combination With Chemoradiation or Stereotactic Body Radiation Therapy for Borderline Resectable Pancreatic Adenocarcinoma

All eligible subjects will be followed for at least 2 additional years from the completion of primary treatment window.

Time from diagnosis until death from any cause.

Time from enrollment until death from any cause.

Time from diagnosis until first objective documentation of progression (local or distant) or death from any cause.

Time from study enrollment to documented disease progression or death from any cause.

Subjects will be considered to have R0 resection if all lesions are removed with negative microscopic surgical margins. Subjects will be considered to have R1 resection if all lesions are removed with any positive microscopic surgical margins.

Disease-free survival (DFS) will be measured from R0 resection until first objective documentation of recurrence or death from any cause.

Immunophenotyping in the blood and in the tissue.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Intratumoral Gene Mediated Cytotoxic Immunotherapy in Patients With Resectable Non-Small Cell Lung Cancer	NCT03131037	Lung Cancer	CAN-2409 + vala...	18 Years -	Candel Therapeutics, Inc.
CAN-2409 Plus Prodrug With Standard of Care Immune Checkpoint Inhibitor for Stage III/IV NSCLC	NCT04495153	Non Small Cell ...	Aglatimagene be...	18 Years -	Candel Therapeutics, Inc.
Neoadjuvant CAN-2409 in Combination With Chemoradiation or SBRT for Borderline Resectable Pancreatic Adenocarcinoma	NCT02446093	Borderline Rese...	Aglatimagene be... Chemoradiation Stereotactic bo... Surgery	18 Years -	Candel Therapeutics, Inc.

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