Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Varlilumab · 2 trials · 6 indications
OS is defined as the time in months between randomization and death, or last follow-up if alive (Groups 1 and 2). Kaplan-Meier methods will be used to estimate median OS
Percentage of patients with unacceptable toxicity (all Groups)
Change between baseline and nadir before the 2nd cycle of TMZ (Combined Groups 1 and 2, Group 3)
| Arm | Type | Description |
|---|---|---|
| Gr1: DC vaccine (DC pre-conditioning) | EXPERIMENTAL | Patients will receive TMZ at a target dose of 150-200 mg/m\^2/d for 5 days every 4 (+2) weeks for up to 12 cycles. DC vaccines will be administered in equal amounts to both inguinal regions. DC vaccines #1-3 occur every 2 weeks and all subsequent vaccines (up to 10) occur monthly. Group 1 patients will receive autologous unpulsed DC vaccines administered to a single side of the groin and saline administered to the contralateral side the day prior to the 4th DC vaccine as pre-conditioning. |
| Gr2: DC Vaccine (Td pre-conditioning) | EXPERIMENTAL | Patients will receive TMZ at a target dose of 150-200 mg/m\^2/d for 5 days every 4 (+2) weeks for up to 12 cycles. DC vaccines will be administered in equal amounts to both inguinal regions. DC vaccines #1-3 occur every 2 weeks and all subsequent vaccines (up to 10) occur monthly. Group 2 patients will receive a single dose of Td toxoid administered to a single side of the groin and saline administered to the contralateral side the day prior to the 4th DC vaccine, which is always given bilaterally at the groin site. |
| Gr3:DC Vaccine+varlilumab(Td pre-conditioning) | EXPERIMENTAL | Patients will receive TMZ at a target dose of 150-200 mg/m\^2/d for 5 days every 4 (+2) weeks for up to 12 cycles. DC vaccines will be administered in equal amounts to both inguinal regions. DC vaccines #1-3 occur every 2 weeks and all subsequent vaccines (up to 10) occur monthly. Group 3 patients will receive the first 3 DC vaccines every 2 weeks, same as Groups 1 and 2, but they will also receive varlilumab intraveneously (IV) 7 days before vaccine #1 and again at the same visit as vaccine #1, as well as 7 days before every DC vaccine except vaccine #2. Prior to the 4th vaccine, patients will receive a single dose of Td toxoid administered to a single side of the groin and saline administered to the contralateral side. |
| Varlilumab and Nivolumab | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Human CMV pp65-LAMP mRNA-pulsed autologous DCs | BIOLOGICAL | 2x10\^7 human CMV pp65-LAMP mRNA-pulsed autologous DCs are given intradermally and bilaterally at the groin site (divided equally to both inguinal regions). Patients will receive up to a total of 10 DC vaccines. |
| Temozolomide | DRUG | Temozolomide is a standard chemotherapy given to all enrolled patients at a targeted dose of 150-200mg/m2/d for 5 days every 4 (+ 2) weeks for up to 12 cycles (patients with unmethylated MGMT gene promoter will receive only cycle 1) |
| Varlilumab | BIOLOGICAL | Varlilumab is an agonist anti-CD27 monoclonal antibody |
| Td | BIOLOGICAL | A single dose of Td toxoid (1 flocculation unit, Lf, in 0.4 mLs) administered to a single side of the groin given intradermally |
| Unpulsed DCs | BIOLOGICAL | Patients in Group I will receive 1 x 10\^6 autologous unpulsed DCs in saline administered to a single side of the groin intradermally 1 day before the fourth vaccine. |
| Combination of varlilumab and nivolumab | DRUG | Phase I: Varlilumab dosing will be dependent on the cohort assigned in combination with 3 mg/kg of nivolumab every two weeks. Phase II: Patients with CRC, RCC or GBM enrolled in Phase ll will receive 3.0 mg/kg of varlilumab in combination with 240 mg of nivolumab every 2 weeks. Patients with SCCHN or ovarian cancer will receive varlilumab at a dose of either 3 mg/kg every 2 weeks, 3 mg/kg every 12 weeks, or 0.3 mg/kg every 4 weeks, in combination with 240 mg of nivolumab every 2 weeks. Patients may be discontinued from receiving study treatment based on the results of disease assessments or if experiencing intolerable side effects. |
Inclusion Criteria: * Age ≥18 years of age. * Glioblastoma with definitive resection prior to enrollment, with residual radiographic contrast enhancing disease on the post-operative CT or MRI of \<1 cm in maximal diameter in any plane. * Able to receive SOC RT/TMZ for approximately 6 weeks duration...
The combination of varlilumab and nivolumab is being studied for the treatment of squamous cell carcinoma of the head and neck (SCCHN). It is an investigational combination therapy in Phase 1 clinical development, evaluated in patients with advanced refractory solid tumors, including SCCHN.
Varlilumab targets CD27, a costimulatory receptor on immune cells, and acts as an agonist. By activating CD27, varlilumab is designed to enhance the immune system's anti-tumor response. It is combined with nivolumab, an anti-PD-1 antibody, in this investigational regimen.
The combination of varlilumab and nivolumab is being developed by Celldex Therapeutics, Inc., a biopharmaceutical company traded on NASDAQ under the ticker symbol CLDX. The therapy is in Phase 1 clinical development for squamous cell carcinoma of the head and neck.
The combination of varlilumab and nivolumab is in Phase 1 clinical development. It is an investigational therapy, not yet approved by regulatory authorities. The Phase 1 study has been completed, with results expected to inform further development.
The combination of varlilumab and nivolumab was studied in a completed Phase 1 clinical trial with the identifier NCT02335918. This trial was a dose escalation and cohort expansion study in advanced refractory solid tumors, including squamous cell carcinoma of the head and neck, with a total enrollment of 175 participants.
Varlilumab is the anti-CD27 antibody component of the combination therapy. The combination of varlilumab and nivolumab refers to the regimen that pairs varlilumab with nivolumab, an anti-PD-1 antibody. Varlilumab alone is a distinct investigational agent, while the combination is the specific therapeutic approach being studied.