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Also known as CAN-2409, AdV-tk
aglatimagene besadenovec · 10 trials · 17 indications
To evaluate whether treatment with aglatimagene besadenovec (CAN-2409) plus valacyclovir and continued pembrolizumab improves overall survival (OS) compared to standard of care (SoC) docetaxel chemotherapy, in participants with Stage IV non-squamous non-small cell lung cancer (NSCLC) whose disease has progressed following prior pembrolizumab-based platinum chemoimmunotherapy
Evaluation of shedding of aglatimagene besadenovec viral genomes in urine, blood, and semen samples using validated bioassays over time.
Tumor response as measured by RECIST criteria including overall response rate (ORR) and/or disease control rate (DCR)
Frequency of adverse events
Progression-free survival is defined as the time from randomization to evidence of histological disease progression or death due to prostate cancer
National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 will be used for scoring toxicity and adverse events. The severity and frequency of toxicity will be tabulated by the tested dose or doses using descriptive statistics. The proportions of subjects who experienced grade 3 or above toxicities will be estimated, along with 95% confidence intervals by each type of toxicity.
| Arm | Type | Description |
|---|---|---|
| Arm 1:Continued pembrolizumab with two courses of Aglatimagene besadenovec plus prodrug | EXPERIMENTAL | Patients continue to receive pembrolizumab with two courses of Aglatimagene besadenovec plus valacyclovir |
| Arm 2: Docetaxel | ACTIVE_COMPARATOR | Patients receive standard of care docetaxel |
| ProstAtak® | EXPERIMENTAL | Aglatimagene besadenovec (CAN-2409) + valacyclovir + radiation therapy +/- ADT |
| Control | PLACEBO_COMPARATOR | Placebo + valacyclovir + radiation therapy +/- ADT |
| Treatment | EXPERIMENTAL | Patients receiving aglatimagene besadenovec + valacyclovir along with External Beam Radiation Therapy (EBRT) |
| Cohorts | OTHER | 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) |
| CAN-2409 | ACTIVE_COMPARATOR | Patients randomized to the active arm will receive two courses of aglatimagene besadenovec (CAN-2409) + valacyclovir |
| Placebo | PLACEBO_COMPARATOR | Patients randomized to the placebo arm will receive two corresponding courses of placebo + valacyclovir |
| Cohort 1: MGMT Unmethylated Patients | EXPERIMENTAL | After confirmation of high grade glioma, AdV-tk injection into wall of resection cavity. Valacyclovir starting 1-3 days post-surgery for 14 days. Radiation begins approximately day 8 and continues for 6 weeks. Temozolomide started after complete valacyclovir and stop when MGMT unmethylated result obtained. Nivolumab every 2 weeks x 26 doses up to 52 weeks. MRI every 8 weeks until progression. |
| Cohort 2: MGMT Methylated & undetermined Patients | EXPERIMENTAL | After confirmation of high grade glioma, AdV-tk injection into wall of resection cavity. Valacyclovir starting 1-3 days post-surgery for 14 days. Radiation begins approximately day 8. Temozolomide started after complete valacyclovir and continue during radiation then 5 week break and then begin adjuvant temozolomide dosing. Nivolumab every 2 weeks x 26 doses up to 52 weeks. MRI every 8 weeks until progression. |
| Study Arm | EXPERIMENTAL | AdV-tk + valacyclovir |
| AdV-tk | EXPERIMENTAL | AdV-tk + valacyclovir in combination with standard of care radiation |
| A resectable | EXPERIMENTAL | Arm A is for resectable tumors. The first AdV-tk course is given prior to surgery by CT or EUS guided injection into the tumor followed by 14 days of valacyclovir. The second AdV-tk injection is into the tumor bed at the time of surgery again followed by 14 days of valacyclovir. |
| B locally advanced | EXPERIMENTAL | Arm B is for locally advanced tumors for which chemoradiation is the planned standard of care treatment. AdV-tk is delivered by CT or EUS guided injection into the tumor. The first AdV-tk injection is given prior to starting chemoradiation and the second in week 3 of chemoradiation. Both injections are followed by 14 days of valacyclovir. Enrollment has been completed for Arm B. |
| A | EXPERIMENTAL | Arm A for unresectable malignant glioma was closed due to poor accrual. |
| B | EXPERIMENTAL | Arm B for resectable malignant glioma completed the Phase I accrual and long term follow up continues. A follow on study at dose level 3 was opened as a Phase 2a study (see BrTK02). |
| Name | Type | Description |
|---|---|---|
| Aglatimagene Besadenovec | BIOLOGICAL | via intratumoral injections into lung or lymph nodes at two timepoints |
| Valacyclovir | DRUG | Oral, for14 days following each aglatimagene besadenovec injection |
| Pembrolizumab | BIOLOGICAL | every 3 weeks (Q3W) or every 6 weeks (Q6W) |
| Docetaxel | DRUG | every 21 days with standard premedication |
| Aglatimagene besadenovec + valacyclovir | BIOLOGICAL | Patients will receive three courses of ProstAtak® each consisting of aglatimagene besadenovec injection + oral valacyclovir. AdV-tk injection will be delivered to the prostate via trans-rectal ultrasound guided injection as follows: 1. The first injection will be given at least 15 days and not more than 8 weeks before starting radiation. 2. The second injection will be 0-3 days before initiation of radiation therapy. 3. The third injection will be 15-22 days after the 2nd injection. The prodrug, valacyclovir, will be administered at a fixed dose for 14 days after each AdV-tk injection. Standard external beam radiation therapy will be delivered to the prostate. Short-term androgen deprivation therapy (maximum of 6 months) is optional but must be decided before enrollment to allow for stratification. |
| Placebo + valacyclovir | BIOLOGICAL | Patients will receive three courses each consisting of placebo injection + oral valacyclovir. Placebo injection will be delivered to the prostate via trans-rectal ultrasound guided injection as follows: 1. The first injection will be given at least 15 days and not more than 8 weeks before starting radiation. 2. The second injection will be 0-3 days before initiation of radiation therapy. 3. The third injection will be 15-22 days after the 2nd injection. The prodrug, valacyclovir, will be administered at a fixed dose for 14 days after each placebo injection. Standard external beam radiation therapy will be delivered to the prostate. Short-term androgen deprivation therapy (maximum of 6 months) is optional but must be decided before enrollment to allow for stratification. |
| External Beam Radiation Therapy (EBRT) | RADIATION | Standard of care standard or moderately hypofractionated prostate-only external beam radiation therapy (EBRT) |
| placebo | BIOLOGICAL | Placebo will be delivered to the prostate via trans-rectal ultrasound guided injection followed by 14 days of oral prodrug, valacyclovir. The second placebo injection will be 2-3 weeks after the first followed by 14 days of valacyclovir. |
| AdV-tk | BIOLOGICAL | Given IT |
| Radiation | RADIATION | Undergo RT, 60Gy in 30 daily fractions M-F for 6weeks |
| Temozolomide | DRUG | Given PO during RT 75mg/m2 daily during RT Post RT cycle 1: 150mg/m2 days 1-5 150mg/m2 cycle 2-6: days 1-5 (150-200mg/m2) |
| Nivolumab | BIOLOGICAL | day 15 post surgery 240mg IV q2wks x 26 doses , up to 52 weeks |
| Laboratory Biomarker Analysis | OTHER | correlative studies |
| AdV-tk + valacyclovir | BIOLOGICAL | AdV-tk will be administered intrapleural through pleural catheter followed by oral valacyclovir. Valacyclovir will be administered orally at a fixed dose for 14 days after each AdV-tk administration. |
Inclusion Criteria: 1. Age ≥ 18 years, at the time of signing the informed consent. 2. Histologically confirmed metastatic Stage IV non-squamous NSCLC. 3. Measurable disease per RECIST v1.1 with at least 1 thoracic lesion amenable to intratumoral injection (e.g., pathological lymph node or lung les...
Aglatimagene besadenovec is an investigational gene therapy being studied in oncology for non-small cell lung cancer, including the non-squamous subtype, and for prostate cancer, including patients treated with radiotherapy. It is given with a prodrug, valacyclovir, and is being evaluated in Phase 2 and Phase 3 clinical trials.
Aglatimagene besadenovec is a gene therapy designed to deliver the HSV-tk gene, which encodes herpes simplex virus thymidine kinase. This enzyme converts the prodrug valacyclovir into a toxic metabolite inside targeted cells, which is intended to kill tumor cells and may stimulate an immune response against the cancer.
Aglatimagene besadenovec is being developed by Candel Therapeutics, Inc., which trades on the Nasdaq under the ticker CADL. The company is the sponsor of the clinical trials evaluating this gene therapy in lung and prostate cancers.
Aglatimagene besadenovec is in Phase 2 and Phase 3 clinical development. It is investigational and has not been approved by the FDA. The FDA has granted it Fast Track designation, which is intended to expedite the review of drugs that treat serious conditions and fill an unmet medical need.
Aglatimagene besadenovec is being studied in several clinical trials, including NCT07660094, a Phase 3 trial in stage IV non-squamous NSCLC, NCT07332000, a Phase 2 biomarker study in localized prostate cancer, NCT04495153, a Phase 2 trial in stage III/IV NSCLC, and NCT02768363, a Phase 2 trial in prostate cancer.
Yes, aglatimagene besadenovec is also known as CAN-2409. It is often referred to with the prodrug valacyclovir, as aglatimagene besadenovec plus valacyclovir. These names refer to the same investigational gene therapy developed by Candel Therapeutics.