Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as anti-CD27, CDX-1127
Varlilumab · 4 trials · 17 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)
Number of participants with dose-limiting toxicities based on CTCAE v5.0
Number of participants with CD4+ T cell responses to 6 MHP persisting to day 127 or later.
Analysis of adverse events along with the results of vital sign measurements, physical examinations, and clinical laboratory tests will be used to determine the safety profile of CDX-1127.
| 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. |
| Arm A: 6MHP/Montanide ISA-51 + polyICLC + CDX-1127 | EXPERIMENTAL | 200 mcg of 6MHP plus 0.9 mg of polyICLC emulsified in Montanide ISA-51 adjuvant will be administered subcutaneously on days 1, 8, 15, and 36. 200 mcg of 6MHP in Montanide ISA-51 adjuvant (without polyICLC) will be administered subcutaneously/intradermally on day 176. CDX-1127 (3mg/kg) will be administered intravenously on days 1, 36, and 78. |
| Arm B: 6MHP/Montanide ISA-51 + polyICLC | EXPERIMENTAL | 200 mcg of 6MHP plus 0.9 mg of polyICLC emulsified in Montanide ISA-51 adjuvant will be administered subcutaneously on days 1, 8, 15, and 36. 200 mcg of 6MHP in Montanide ISA-51 adjuvant (without polyICLC) will be administered subcutaneously/intradermally on day 176. |
| Varlilumab and Nivolumab | EXPERIMENTAL | - |
| Hematologic Malignancies (Dose Escalation) | EXPERIMENTAL | B-Cell Enrollment COMPLETED T-Cell Enrollment COMPLETED |
| Solid tumors (Dose Escalation; COMPLETED) | EXPERIMENTAL | - |
| Solid Tumors (Expansion Phase; COMPLETED) | EXPERIMENTAL | Several expansion cohorts of up to 15 patients each are planned, including melanoma and renal cell carcinoma. |
| Hematologic Malignancies (COMPLETED) | EXPERIMENTAL | Several expansion cohorts of up to 15 patients each are planned, including Hodgkin lymphoma. |
| 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. |
| 6MHP | BIOLOGICAL | 6 melanoma helper vaccine comprised of 6 class II MHC-restricted helper peptides |
| Montanide ISA-51 | DRUG | Montanide ISA-51 (Incomplete Freund's Adjuvant), local adjuvant |
| polyICLC | DRUG | polyICLC, local adjuvant |
| CDX-1127 | DRUG | CDX-1127, anti-CD27 monoclonal antibody |
| 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...
Varlilumab is an investigational monoclonal antibody being studied in oncology for glioblastoma and squamous cell carcinoma of the head and neck. It is also being evaluated in combination with nivolumab in advanced refractory solid tumors. It is not approved for any indication and remains in clinical development.
Varlilumab targets CD27, a costimulatory receptor on T cells. It acts as an agonist, meaning it activates CD27 signaling to enhance T-cell activation and antitumor immune responses. This mechanism is being explored in several solid tumor types.
Varlilumab is being developed by Celldex Therapeutics, Inc., which trades on the Nasdaq under the ticker CLDX. The company is the sponsor of the clinical trials evaluating the drug in glioblastoma and other advanced solid tumors.
Varlilumab is in Phase 2 clinical development. It has not been approved by the FDA or any regulatory agency. The Phase 2 trial is evaluating the drug in glioblastoma, while a completed Phase 1 trial studied it in combination with nivolumab in advanced solid tumors.
Varlilumab has been studied in two clinical trials. NCT03688178 is an active Phase 2 trial in glioblastoma evaluating TReg depletion with and without varlilumab. NCT02335918 was a completed Phase 1 dose escalation and cohort expansion trial of varlilumab plus nivolumab in advanced refractory solid tumors, including SCCHN.