Approval Probability
TA Base Rate
Adjusted LOA
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aglatimagene besadenovec · 5 trials · 4 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
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
Frequency of adverse events.
All eligible subjects will be followed for at least 2 additional years from the completion of primary treatment window.
| 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 |
| 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 |
| Test Arm | EXPERIMENTAL | CAN-2409 + prodrug (valacylovir or acyclovir) in combination with neoadjuvant chemoradiation or SBRT + Surgery |
| Control Arm | ACTIVE_COMPARATOR | Neoadjuvant chemoradiation or SBRT + Surgery |
| 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. |
| 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. |
| Chemoradiation | RADIATION | 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. |
| Stereotactic body radiation therapy | RADIATION | 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. |
| Surgery | PROCEDURE | Surgical resection should be performed within 8 weeks after completing CR or SBRT. |
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...
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