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NCT03268057 (opened Oct 2017) |
VX15/2503 (anti-Semaphorin 4D/SEMA4D mAb) in combination with avelumab in advanced NSCLC |
Phase Ib/II, 3 + 3 dose escalation/dose expansion Stage IIIB/IV NSCLC with progression on cytotoxic chemotherapy VX15/2503 dose escalation 5 mg/kg to 15 mg/kg, biweekly dosing cycle Biweekly IV avelumab (10 mg/kg) |
1° EP: number of DLTs per dose level, frequency of AEs 2° EP: ORR, DoR, PFS at 2 yr Immunogenicity of VX15/2503 + avelumab by titer of anti-drug antibodies |
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NCT03260023 (opened Sept 2017) |
Combination of TG4001 and Avelumab in HPV-16 + oropharyngeal HNSCC |
Phase Ib/II, 3 + 3 dose escalation/dose expansion Recurrent/unresectable or metastatic HPV-16+ cancer, prior platinum required (≤ 2 prior systemic therapies) Phase II expansion cohort of oropharyngeal HNSCC TG4001 (MVA-HPV-IL2) is a modified vaccinia virus Ankara vector encoding HPV-16 E6/E7 antigens and IL-2 adjuvant |
1° EP: DLTs, AEs/ORR [phase II] 2° EP: ORR, DoR, PFS, DCR |
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NCT02994953 (opened Jan 2017) |
Avelumab in combination with NHS-IL12 (M9241) in solid tumors |
Phase Ib, dose-finding Recurrent/unresectable or metastatic solid tumors; part B will enroll post-platinum UC, 1st line mNSCLC, recurrent/refractory CRC (MSS only), RCC after immune checkpoint failure NHS-IL12 SC injection day 1 each cycle (ly) and biweekly IV avelumab (days 1 and 15) |
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NCT02584829 (opened Nov 2015) |
Avelumab in combination with MHC upregulation (intratumoral IFNβ or RT) ± adoptive transfer of MCPyV TAg-specific CD8+ T-cells in metastatic Merkel Cell Carcinoma |
Phase I/II, metastatic Merkel Cell Carcinoma MHC upregulation: localized RT or intra-tumoral IFNβ, delivered 7–10 days after first dose of avelumab (IV biweekly up to 1 year) Adoptive T-cell transfer: two infusions of MCPyV TAg-specific polyclonal autologous CD8+ T-cells, delivered 2–5 days after avelumab |
1° EP: time to new metastasis (response), AEs 2° EP: response per RECIST v1.1 Epitope spreading and recognition of MCPyV TAg In vivo persistence/functionality of transferred T-cells |
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NCT03217747 (opened Aug 2017) |
Avelumab in combination with other anti-cancer therapies in advanced malignancies |
Phase I/II, avelumab combined with checkpoint agonists ± RT or cisplatin/RT of limited/locally advanced/metastatic solid tumors Arm A: avelumab (IV 10 mg/kg q2wks) + anti-4-1BB/utomilumab (IV 100 mg q4wks Arm B: avelumab + OX40 agonist [PF-04518600] (IV 0.3 mg/kg q2wks) Arm C: avelumab + anti-4-1BB + OX40 agonist (IV 0.1 mg/kg q2wks) Arm D: avelumab + anti-4-1BB + RT (6 Gy × 10) Arm E: avelumab + OX40 agonist + RT (6 Gy × 10) Arm F: avelumab + anti-4-1BB + OX40 agonist + RT (6 Gy × 10) Arm G: avelumab + cisplatin (IV 40 mg/m2)/RT (1.8 Gy × 25) |
1° EP: MTD, AEs, changes in CD8 expression before/after treatment – correlated clinical benefit with response 2° EP: ORR per RECIST and irRC, PFS, DoR, OS |
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NCT02554812 (opened Nov 2015) |
Avelumab in combination with other cancer immunotherapies in advanced malignancies (JAVELIN Medley) |
Phase Ib/II – locally advanced/metastatic solid tumors with progression on SOC or without treatment options; NSCLC, melanoma, HNSCC, TNBC, CRC, gastric cancer, ovarian cancer, UC. Cohort A: avelumab + anti-4-1BB/utomilumab Cohort B: avelumab + OX40 agonist (PF-04518600) Cohort C: avelumab + anti-M-CSF (PD-0360324) Cohort D: avelumab + anti-4-1BB + OX40 agonist |
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NCT03050814 (opened Apr 2017) |
Ad-CEA vaccine and Avelumab in previously untreated mCRC |
Randomized phase II, mCRC-MSS [lacking mismatch repair deficiency] Arm A: SOC = FOLFOX + bevacizumab followed by bevacizumab + capecitabine maintenance Arm B: SOC + avelumab + Ad-CEA vaccine (SC injection) + SOC Ad-CEA, adenovirus-based CEA-targeting vaccine |
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NCT02951156 (opened Dec 2016) |
Combination regimens of immunotherapy, epigenetic modulator and CD20-antagonist or chemotherapy in refractory/relapsed DLBCL (JAVELIN DLBCL) |
Phase Ib/III, relapsed/refractory DLBCL, ≤4 prior lines of rituximab-containing multi-agent chemotherapy or ASCT failure/ineligible. Arm D selected based on phase Ib arm A–C, will enter phase III randomization vs SOC (arm E) Arm A: avelumab + utomilumab + rituximab Arm B: avelumab + utomilumab + azacitidine Arm C: avelumab + rituximab + bendamustine phase III: Arm D vs Arm E (rituximab/bendamustine or rituximab/gemcitabine/oxaliplatin) |
1° EP: DLT, ORR (phase Ib); PFS [phase III] 2° EP: DoR, TTR, DCR, PFS, OS, minimal residual disease [phase Ib]; OS, PFS, ORR, TTR, DoR, DCR [phase III] PD-L1 expression levels on tumor cells and TIL at baseline |
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NCT03136406 (opened Dec 2017) |
Combination immunotherapy with aNK in pancreatic cancer with progression on/after SOC |
Phase Ib/II, pancreatic cancer patients with PD after prior SOC chemotherapy Combination: ALT-803, ETBX-011, GI-4000, aNK, avelumab, multi-agent chemo Vaccines: ETBX-011 (CEA-targeting vaccine), GI-4000 (recombinant S. cerevisiae yeast-vaccine expressing mutant Ras proteins) ALT-803, IL-15 superagonist, aNK, activated NK cells engineered to not express killer inhibitory receptors (KIR) |
1° EP: treatment-related AEs [phase Ib]; ORR by RECIST and irRC [phase II] 2° EP: ORR/PFS by RECIST/irRECIST, OS, DoR, DCR [phase Ib]; PFS/OS, DoR, DCR, patient-reported outcomes, treatment-related AEs |
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NCT03329248 (opened Nov 2017) |
Combination immunotherapy with haNK in pancreatic cancer with progression on/after SOC |
Phase Ib/II, pancreatic cancer patients with PD after prior SOC chemotherapy. Phase II is Simon’s two-stage optimal design; those with CR during induction phase will enter maintenance phase Combination: ALT-803, ETBX-011, GI-4000, haNK, avelumab, multi-agent chemo, SBRT Vaccines: ETBX-011 (CEA-targeting vaccine), GI-4000 (Ras-mutant targeting S. cerevisiae yeast-vaccine) ALT-803, IL-15 superagonist, haNK, modified NK cells to express high-affinity CD16 to potentiate ADCC |
1° EP: treatment-related AEs [phase Ib]; ORR by RECIST [phase II] 2° EP: ORR, PFS by RECIST/irRECIST, OS, DoR, DCR [phase Ib]; PFS by RECIST/irRC, OS, DoR, DCR, patient-reported outcomes |
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