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New Immunotherapy Approaches for The Treatment of Cancer: Reported at the European Society for Medical Oncology Congress 2018

| Oncology
Authors:
Philippe Aftimos, Christiane Jungels, Nuria Kotecki, Leila Shaza, *Ahmad Awada
Disclosure:

Dr Jungels declares travel expenses from Pharmamar and Bayer. Dr Awada declares advisory board honorarium from Cantargia. Dr Aftimos declares travel expenses from Roche and MSD; speaker’s fees from Amgen and Novartis; and advisory board and consultant fees from Boehringer Ingleheim, Macrogenics, and Synthon. The remaining authors declare no conflicts of interest.

Citation
EMJ Oncol. ;6[1]:75-76. Abstract Review No. AR4.

Each article is made available under the terms of the Creative Commons Attribution-Non Commercial 4.0 License.

Immunotherapy is currently a pillar in the treatment of cancer, in addition to surgery, radiotherapy, chemotherapy, and molecular-targeted therapies.

Our team, in collaboration with other investigators, reported the results of four important early clinical trials involving innovative immunotherapeutic approaches at the European Society for Medical Oncology (ESMO) Congress 2018 in Munich, Germany.

Flament et al.1 reported Phase I studies assessing the safety and clinical activity of multiple doses of a NKG2D-based chimeric antigen receptor T cell therapy, CYAD-01, in metastatic solid tumours, in particular colorectal cancer and haematological malignancies. The THINK study, which is investigating chimeric antigen receptor T cell therapy without preconditioning, demonstrated the feasibility of multiple doses;2 however, it is too early to conclude on the anti-tumour activity of this approach. Two other studies are ongoing, one of them in combination with neoadjuvant FOLFOX in colorectal cancer (SHRINK study).3

Awada et al.4 reported a first-in-class, first-in-human Phase I/IIa trial of CAN04, a monoclonal antibody targeting IL-1 receptor accessory protein (IL1RAP), in patients with solid tumours. IL1RAP is a coreceptor for the IL-1 receptor, which is expressed on human cancer cells. CAN04 showed mainly infusion-related adverse events mitigated with a reduced priming dose of CAN04 and premedication. An expansion cohort is expected with a single agent and in combination with chemotherapy in non-small cell lung cancer and advanced pancreatic cancer.

Cho et al.5 presented data on M7824, a bifunctional fusion protein targeting programmed death ligand 1 and TGF-β in patients with advanced squamous cell carcinoma of the head and neck. In summary, M7824 showed promising early clinical activity and a manageable safety profile. In this trial, an objective response rate of 22% was observed with a possible trend toward higher activity in human papilloma virus-positive tumours and evidence of clinical activity irrespective of programmed death ligand 1 status.

Finally, Awada et al.6 reported the results of the translational part of a Phase I trial with copanlisib, a phosphoinositide 3-kinase (PI3K) inhibitor, and how this inhibition modulates the immune and tumour microenvironment in patients with non-Hodgkin lymphoma (NHL) or advanced solid tumours. The conclusion was that high prevalence of the PI3K isoforms, especially α in both NHL and solid tumours, and δ in NHL, is consistent with a role for PI3K signalling in immune suppression. The immune modulation profile of copanlisib supports combination studies with immunotherapy.

References
Flament A et al. Phase 1 studies assessing the safety and clinical activity of multiple doses of a NKG2D-based CAR-T therapy, CYAD-01, in metastatic colorectal cancer. Ann Oncol. 2018;29(suppl_8):viii150-204. Celyad. A dose escalation Phase I study to assess the safety and clinical activity of multiple cancer indications (THINK). NCT03018405. https://clinicaltrials.gov/ct2/show/NCT03018405. Celyad. Dose Escalation and Dose Expansion Phase I Study to Assess the Safety and Clinical Activity of Multiple Doses of NKR-2 Administered Concurrently With FOLFOX in Colorectal Cancer With Potentially Resectable Liver Metastases (SHRINK). NCT03310008. https://clinicaltrials.gov/ct2/show/NCT03310008. Awada A et al. A first-in-class, first-in-human Phase I/IIa trial of CAN04, targeting interleukin-1 receptor accessory protein (IL1RAP), in patients with solid tumors. Ann Oncol. 2018;29(suppl 8):viii400-41. Cho BC et al. M7824 (MSB0011359C), a bifunctional fusion protein targeting PD-L1 and TGF-β , in patients (pts) with advanced SCCHN: Results from a Phase 1 cohort. Ann Oncol. 2018;29(suppl 8): viii372-99. Awada A et al. PI3K inhibition and modulation of immune and tumor microenvironment markers by copanlisib in patients with non-Hodgkin's lymphoma or advanced solid tumors. Ann Oncol. 2018;29(suppl_8):viii14-57.