eRapport

Development of novel cancer treatment combining checkpoint inhibitors with immunogenic chemo- or radiotherapy

Prosjekt
Prosjektnummer
2017100
Ansvarlig person
Jon Amund Kyte
Institusjon
Oslo universitetssykehus HF
Prosjektkategori
Karrierestipend
Helsekategori
Cancer
Forskningsaktivitet
5. Treatment Developement, 6. Treatment Evaluation
Rapporter
2024
Immunotherapy represents an important novel development within cancer treatment. In the present project, we conduct clinical trials, investigating checkpoint inhibitor therapy and the combination with immunogenic chemo- or radiotherapy. We also study biomarkers and develop immunotherapy with retargeted T cells against solid cancers.We have completed three clinical trials initiated by JA Kyte in 2016-2018, ALICE, REPORT and ICON. These trials combining immunological checkpoint inhibitors with established treatment modalities (chemotherapy, radiotherapy) in Breast Cancer (BC) or Head and Neck Squamous Cell Carcinoma (HNSCC). Our approach is to induce personalized immune responses by selected immunogenic chemo- or radiotherapy, and to release the brake on this immune response with PD-1/PD-L1 and/or CTLA-4 blockade. Previously, we have together with partners across Norway completed the IPI4trial, evaluating ipilimumab in a real world melanoma population. The ALICE-trail was published in Nature Medicine Dec 2023 (corresponding author JA Kyte). ALICE was a randomized phase IIb study in subjects with metastatic TNBC. ICON was a randomized phase IIb study where patients with HR+ BC were randomized to: Arm A: Chemotherapy. Arm B: Chemotherapy + ipilimumab (ipi; aCTLA4) + nivolumab (nivo: aPD-1). The trial also included a nested study of ipi+nivo without concomitant chemotherapy. The initial results were reported as an oral presentation at ESMO, Paris, 2022. The full clinical data set was published Jan 2024 in JITC. Andreas Røssevold (main supervisor JA Kyte) defended his PhD in 2024, on the ALICE and ICOIN trials, and an immune biomarker study. REPORT was a singel-arm phase I/II study evaluating the safety and efficacy of nivolumab when combined with re-irradiation in 20 patients with recurrent HNSCC. Primary objectives: 1) Safety and tolerability 2) To determine a safe dose of nivolumab when administered concomitant with re-irradiation. A manuscript is under preparation. The clinical data from the IPI4 trial has been published in two papers in 2021/2022. Elin Aamdal (main supervisor JA Kyte) completed her PhD on the Ipi4-project in 2022. In 2024, we published an article on translational work from IPI4, describing cytokine profiles and their dynamics and association with clinical outcome. Further analyses of data from IPI4 are ongoing, including the analyses of biomarkers. We also published data from a collaborative European melanoma study. The ALICE, ICON and REPORT trials include cutting edge translational sub-projects, building on extensive collection of biopsies and peripheral blood samples. This translational work resulted in three original research articles in 2024. Moreover, we have conducted a biomarker study in early breast cancer (Røssevold et al, in press). We further aim at bringing CAR T cell therapy to solid cancers. To achieve this, we target unexplored tumor antigens and develop novel concepts for harnessing CAR T cells and countering tumor tolerance. We are developing CARs against new targets in prostate cancer and breast cancer, and explore combinatory strategies for increased therapeutic effectiveness. Progress: We have developed a series of CARs against two new targets, and showed that these CARs are expressed in T cells and functional in vitro and in vivo. The CAR T cells effectively and specifically kill cancer cells expressing the relevant target, and controls tumor in xenograft mouse models, that we have established as part of this project. Further, we have developed a construct countering a common mechanism for tumor tolerance and showed that this construct is functional in T cells. These projects have resulted in four original research publications in 2022-2024. A clinical trial is under preparation, with one of the CAR T products.

nei

2023
Immunotherapy represents an important novel development within cancer treatment. In the present project, we conduct clinical trials, investigating checkpoint inhibitor therapy and the combination with immunogenic chemo- or radiotherapy. We also develop immunotherpay with retargeted T cells against solid cancers.We have in 2022 completed three clinical trials initiated by JA Kyte in 2016-2018, ALICE, REPORT and ICON. These trials combining immunological checkpoint inhibitors with established treatment modalities (chemotherapy, radiotherapy) in Breast Cancer (BC) or Head and Neck Squamous Cell Carcinoma (HNSCC). Our approach is to induce personalized immune responses by selected immunogenic chemo- or radiotherapy, and to release the brake on this immune response with PD-1/PD-L1 and/or CTLA-4 blockade. Previously, we have together with partners across Norway completed the IPI4trial, evaluating ipilimumab in a real world melanoma population. The ALICE-trail was published in Nature Medicine Dec 2023 (corresponding author JA Kyte). ALICE was a randomized phase IIb study in subjects with metastatic TNBC. The patients were included and randomized 2:3, as follows: • Arm A: Chemo (Caelyx + cyclophosphamide) + placebo • Arm B: Chemo (Caelyx + cyclophosphamide) + atezolizumab. ICON was a randomized phase IIb study where patients with HR+ BC were randomized to: Arm A: Chemotherapy. Arm B: Chemotherapy + ipilimumab (ipi; aCTLA4) + nivolumab (nivo: aPD-1). The trial also included a nested study of ipi+nivo without concomitant chemotherapy. The initial results were reported as an oral presentation at ESMO, Paris, 2022. The full clinical data set, including both the randoimized part and the substudy of ipi+nivo without chemo, were published Jan 2024 in JITC (https://doi.org/10.1136/jitc-2023-007990) REPORT was a singel-arm phase I/II study evaluating the safety and efficacy of nivolumab when combined with re-irradiation in 20 patients with recurrent HNSCC. Primary objectives: 1) Safety and tolerability 2) To determine a safe dose of nivolumab when administered concomitant with re-irradiation. Progress: The clinical trial and data read out has been completed. A manuscript is under preparation. The clinical data from the IPI4 trial has been published in two papers in 2021/2022. Elin Aamdal (main supervisor JA Kyte) completed her PhD on the Ipi4-project in 2022. Further analyses of data from IPI4 are ongoing, including the analyses of biomarkers. The ALICE, ICON and REPORT trials include cutting edge translational sub-projects, building on extensive collection of biopsies and peripheral blood samples. We further aim at bringing CAR T cell therapy to solid cancers. To achieve this, we target unexplored tumor antigens and develop novel concepts for harnessing CAR T cells and countering tumor tolerance. We are developing CARs against new targets in prostate cancer and breast cancer, and explore combinatory strategies for increased therapeutic effectiveness. Progress: We have developed a series of CARs against two new targets, and showed that these CARs are expressed in T cells and functional in vitro and in vivo. The CAR T cells effectively and specifically kill cancer cells expressing the relevant target, and controls tumor in xenograft mouse models, that we have established as part of this project. Further, we have developed a construct countering a common mechanism for tumor tolerance and showed that this construct is functional in T cells. These projects resulted in two original research publications in 2022, and one more in 2023.

nei

2022
Immunotherapy represents an important novel development within cancer treatment. In the present project, we conduct clinical trials, investigating checkpoint inhibitor therapy and the combination with immunogenic chemo- or radiotherapy. We also develop immunotherpay with retargeted T cells against solid cancers.We have in 2022 completed three clinical trials initiated by JA Kyte in 2016-2018, ALICE, REPORT and ICON. These trials combining immunological checkpoint inhibitors with established treatment modalities (chemotherapy, radiotherapy) in Breast Cancer (BC) or Head and Neck Squamous Cell Carcinoma (HNSCC). Our approach is to induce personalized immune responses by selected immunogenic chemo- or radiotherapy, and to release the brake on this immune response with PD-1/PD-L1 and/or CTLA-4 blockade. Previously, we have together with partners across Norway completed the IPI4trial, evaluating ipilimumab in a real world melanoma population. The ALICE-trail was published in Nature Medicine Dec 2023 (corresponding author JA Kyte). ALICE was a randomized phase IIb study in subjects with metastatic TNBC. The patients were included and randomized 2:3, as follows: • Arm A: Chemo (Caelyx + cyclophosphamide) + placebo • Arm B: Chemo (Caelyx + cyclophosphamide) + atezolizumab. The ICON trial was completed in 2022 and the initial results were reported as an oral presentation at ESMO, Paris, 2022. The clinical data has been analysed and a manuscript has been submitted for publication. ICON was a randomized phase IIb study where patients with HR+ BC were randomized to: Arm A: Chemotherapy (Caelyx + cyclophosphamide) Arm B: Chemotherapy + ipilimumab (ipi; aCTLA4) + nivolumab (nivo: aPD-1). REPORT was a singel-arm phase I/II study evaluating the safety and efficacy of nivolumab when combined with re-irradiation in 20 patients with recurrent HNSCC. Primary objectives: 1) Safety and tolerability 2) To determine a safe dose of nivolumab when administered concomitant with re-irradiation. Progress: The clinical trial and data read out has been completed in 2022 The clinical data from the IPI4 trial has been published in two papers in 2021/2022. Elin Aamdal (main supervisor JA Kyte) completed her PhD on the Ipi4-project in 2022. Further analyses of data from IPI4 are ongoing, including the analyses of biomarkers. The ALICE, ICON and REPORT trials include cutting edge translational sub-projects, building on extensive collection of biopsies and peripheral blood samples. The methods for investigating biomarkers and immune responses are being established. This includes CyTOF, flow cytometry, gene profiling, Hyperion Imaging Mass Cytometry. We further aim at bringing CAR T cell therapy to solid cancers. To achieve this, we target unexplored tumor antigens and develop novel concepts for harnessing CAR T cells and countering tumor tolerance. We are developing CARs against new targets in prostate cancer and breast cancer, and explore combinatory strategies for increased therapeutic effectiveness. Progress: We have developed a series of CARs against two new targets, and showed that these CARs are expressed in T cells and functional in vitro and in vivo. The CAR T cells effectively and specifically kill cancer cells expressing the relevant target, and controls tumor in xenograft mouse models, that we have established as part of this project. Further, we have developed a construct countering a common mechanism for tumor tolerance and showed that this construct is functional in T cells. These projects resulted in two original research publications in 2022, where JA Kyte was the corresponding author.

na

2021
Immunotherapy represents an important novel development within cancer treatment. In the present project, we conduct three clinical trials, investigating novel strategies for combing checkpoint inhibitors with immunogenic chemo- or radiotherapy. We also develop immunotherpay with retargeted T cells against solid cancers.Immunotherapy represents an important novel development within cancer treatment. In the present project, we conduct clinical trials, investigating checkpoint inhibitor therapy and the combination with immunogenic chemo- or radiotherapy. We also develop immunotherpay with retargeted T cells against solid cancers. We have together with partners accross Norway completed the IPI4trial, evaluating ipilimumab in a real world melanoma population. Further, we started three clinical trials in 2017/2018, ALICE, REPORT and ICON combining immunological checkpoint inhibitors with established treatment modalities (chemotherapy, radiotherapy) in Breast Cancer (BC) or Head and Neck Squamous Cell Carcinoma (HNSCC). Intriguingly, though chemo- or radiotherapy may induce transient tumor regression by direct killing of cancer cells, compelling evidence suggests that the long term effect often depends on mobilizing the host immune system. Our approach is to induce personalized immune responses by selected immunogenic chemo- or radiotherapy, and to release the brake on this immune response with PD-1/PD-L1 and/or CTLA-4 blockade. ALICE is a randomized phase IIb study in subjects with metastatic TNBC. The patients were included and randomized 2:3, as follows: • Arm A: Chemo (Caelyx + cyclophosphamide) + placebo • Arm B: Chemo (Caelyx + cyclophosphamide) + atezolizumab. ICON is a randomized phase IIb study where patients with HR+ BC were randomized to: Arm A: Chemotherapy (Caelyx + cyclophosphamide) Arm B: Chemotherapy + ipilimumab (ipi; aCTLA4) + nivolumab (nivo: aPD-1). In both ALICE and ICON, the primary objectives are: 1) Progression-free survival 2) Toxicity. Progress: The clinical data from the IPI4 trial has been finalized, quality controlled and analysed, and were published in 2022. Further analyses of data from IPI4 are ongoing, including the analyses of biomarkers and of patient reported outcomes. We completed the enrollment of patients into ALICE December 2021. A total of 70 patients were included, of which 68 started therapy. The enrollment was stopped before the planned 75 patients, because the study drug atezolizumab has become standard therapy for TNBC in Norway. Enrollment of patients into the ICON trial was completed November 2020 and we expect data read out for the clinical endpoints in 2022. REPORT is a singel-arm phase I/II study evaluating the safety and efficacy of nivolumab when combined with re-irradiation in 20 patients with recurrent HNSCC. Primary objectives: 1) Safety and tolerability 2) To determine a safe dose of nivolumab when administered concomitant with re-irradiation. Progress: The enrollement of patients in the REPORT trial was completed December 2020. The clinical data read out is expected in 2022. The ALICE, ICON and REPORT trials include cutting edge translational sub-projects, building on extensive collection of biopsies and peripheral blood samples. Through a carefully assembled team, we are able to address a series of important challenges within the field. The methods for investigating biomarkers and immune responses are being established. This includes CyTOF, flow cytometry, gene profiling, Hyperion Imaging Mass Cytometry. We further aim at bringing CAR T cell therapy to solid cancers. To achieve this, we target unexplored tumor antigens and develop novel concepts for harnessing CAR T cells and countering tumor tolerance. We are developing CARs against new targets in prostate cancer and breast cancer, and explore combinatory strategies for increased therapeutic effectiveness. Progress: We have developed a series of antibodies and CARs against two new targets, and showed that these CARs are expressed in T cells and functional in vitro and in vivo. The CAR T cells effectively and specifically kill cancer cells expressing the relevant target, and controls tumor in xenograft mouse models, that we have established as part of this project. Further, we have developed a construct countering a common mechanism for tumor tolerance and showed that this construct is functional in T cells.

nei

2020
Immunotherapy represents an important novel development within cancer treatment. In the present project, we conduct three clinical trials, investigating novel strategies for combing checkpoint inhibitors with immunogenic chemo- or radiotherapy. We also develop immunotherpay with retargeted T cells against solid cancers.We started three clinical trials in 2017/2018, ALICE, REPORT and ICON combining immunological checkpoint inhibitors with established treatment modalities (chemotherapy, radiotherapy) in Breast Cancer (BC) or Head and Neck Squamous Cell Carcinoma (HNSCC). Intriguingly, though chemo- or radiotherapy may induce transient tumor regression by direct killing of cancer cells, compelling evidence suggests that the long term effect often depends on mobilizing the host immune system. Our approach is to induce personalized immune responses by selected immunogenic chemo- or radiotherapy, and to release the brake on this immune response with PD-1/PD-L1 and/or CTLA-4 blockade. ALICE is a randomized phase IIb study in subjects with metastatic TNBC. A total of 75 patients will be included and randomized 2:3, as follows: • Arm A (n=30): Chemo (Caelyx + cyclophosphamide) + placebo • Arm B (n=45): Chemo (Caelyx + cyclophosphamide) + atezolizumab. ICON is a randomized phase IIb study where 75 patients with HR+ BC are randomized to: Arm A: Chemotherapy (Caelyx + cyclophosphamide) Arm B: Chemotherapy + ipilimumab (ipi; aCTLA4) + nivolumab (nivo: aPD-1). In both ALICE and ICON, the primary objectives are: 1) Progression-free survival 2) Toxicity. Progress: The inclusion of patients has been affected by the Covid19 outbreak. Still, we completed enrollment of patients into the ICON trial November 2020 and expect data read out for the clinical endpoints in 2022. The inclusion of patients into ALICE has been reduced after the approval of atezolizumab fro PD-L1+ TNBC April 2020. We have to date enrolled 56 patients into ALICE. REPORT is a singel-arm phase I/II study evaluating the safety and efficacy of nivolumab when combined with re-irradiation in 20 patients with recurrent HNSCC. Primary objectives: 1) Safety and tolerability 2) To determine a safe dose of nivolumab when administered concomitant with re-irradiation. Progress: The enrollment of patients in the REPORT trial was completed December 2020. The primary clinical data read out is expected Q4 2021. The ALICE, ICON and REPORT trials include cutting edge translational sub-projects, building on extensive collection of biopsies and peripheral blood samples. Through a carefully assembled team, we are able to address a series of important challenges within the field. The methods for investigating biomarkers and immune responses are being established. This includes CyTOF, flow cytometry, gene profiling, Hyperion Imaging Mass Cytometry. We further aim at bringing CAR T cell therapy to solid cancers. To achieve this, we target unexplored tumor antigens and develop novel concepts for harnessing CAR T cells and countering tumor tolerance. We are developing CARs against new targets in prostate cancer and breast cancer, and explore combinatory strategies for increased therapeutic effectiveness. Progress: We have developed a series of CARs against two new targets, and showed that these CARs are expressed in T cells and functional in vitro and in vivo. The CAR T cells effectively and specifically kill cancer cells expressing the relevant target, and controls tumor in xenograft mouse modles, that we have established as part of this project. Further, we have developed a construct countering a common mechanism for tumor tolerance and showed that this construct is functional in T cells.

nei

2019
Immunotherapy represents an important novel development within cancer treatment. In the present project, we conduct three clinical trials, investigating novel strategies for combing checkpoint inhibitors with immunogenic chemo- or radiotherapy. We also develop immunotherpay with retargeted T cells against solid cancers.Immunotherapy with antibodies blocking the checkpoint PD-1/PD-L1 show remarkable clinical activity against several cancer forms. These drugs enhance the patient´s anti-tumor immune response. However, in most cancer forms, only a minority of patients respond. In the present project, we investigate novel strategies for combing checkpoint inhibitors with chemo-and radiotherapy. We have started three clinical trials in 2017/2018, ALICE, REPORT and ICON combining immunological checkpoint inhibitors with established treatment modalities (immunogenic chemotherapy, radiotherapy). Intriguingly, though chemo- or radiotherapy may induce transient tumor regression by direct killing of cancer cells, compelling evidence suggests that the long term effect often depends on mobilizing the host immune system. Our approach is to induce personalized immune responses by selected immunogenic chemo- or radiotherapy, and to release the brake on this immune response with PD-1/PD-L1 and/or CTLA-4 blockade. We focus on patients with poor prognosis, thus addressing huge medical needs. In the trials, we employ regimes that are already accepted as 1st line therapy. This allows for evaluating the effects in patients that have not received multiple lines of therapy and are more likely to respond. ALICE is a randomized, double-blind, placebo-controlled phase IIb study evaluating the efficacy and safety of atezolizumab when combined with immunogenic chemotherapy in subjects with metastatic TNBC. A total of 75 patients will be included and randomized 2:3, as follows: • Arm A (n=30): Chemo (Caelyx + cyclophosphamide) + placebo • Arm B (n=45): Chemo (Caelyx + cyclophosphamide) + atezolizumab. ICON is a randomized open label phase IIb study where 75 patients with HR+ BC, eligible for 1st/2nd line of chemotherapy, are randomized to: Arm A: Chemotherapy (Caelyx + cyclophosphamide) Arm B: Chemotherapy + ipilimumab (ipi; aCTLA4) + nivolumab (nivo: aPD-1). In both ALICE and ICON, the primary objective are: 1) Progression-free survival 2) Toxicity. Progress: We have to date included 46 patients in the ALICE-trial, and 54 patients in the ICON trial. REPORT is a singel-arm, open label phase I/II study evaluating the safety and efficacy of nivolumab when combined with re-irradiation in 20 patients with recurrent HNSCC. Primary objectives: 1) Safety and tolerability of nivolumab administered concomitant with re-irradiation in HNSCC 2) To determine a safe dose of nivolumab when administered concomitant with re-irradiation. Progress: We have to date included 16 patients in the REPORT trial. The ALICE, ICON and REPORT trials include cutting edge translational sub-projects, building on extensive collection of biopsies and peripheral blood samples. Through a carefully assembled team, we are able to address a series of important challenges within the field. The methods for investigating biomarkers and immune responses are being established. This includes CyTOF, flow cytometry, gene profiling, IHC. We further aim at bringing CAR T cell therapy to solid cancers. To achieve this, we target unexplored tumor antigens and develop novel concepts for harnessing CAR T cells and countering tumor tolerance. We are developing CARs against new targets in prostate cancer and breast cancer, and explore combinatory strategies for increased therapeutic effectiveness.

nei

2018
Immunotherapy represents an important novel development within cancer treatment. In particular, antibodies blocking the immune checkpoints show remarkable clinical activity. In the present project, we conduct two clinical trials, investigating novel strategies for combing checkpoint inhibitors with immunogenic chemo- or radiotherapy.Immunotherapy with antibodies blocking the checkpoint PD-1/PD-L1 show remarkable clinical activity against several cancer forms. These drugs enhance the patient´s anti-tumor immune response. However, in most cancer forms, only a minority of patients respond. In the present project, we investigate novel strategies for combing checkpoint inhibitors with chemo-and radiotherapy. We have started two clinical trials: • ALICE: A randomized placebo-controlled phase II study evaluating PD-L1 blockade combined with immunogenic chemotherapy in patients with metastatic triple negative breast cancer (mTNBC) • REPORT: REirradiation and PD-1 blockade On Recurrent head and neck squamous cell carcinoma (HNSCC) Intriguingly, the host immune response is strongly predictive for the effect of chemotherapy in mTNBC. In the ALICE trial, we aim at releasing the brake on the immune response by combining PD1/PD-L1 blockade with selected chemotherapy known to induce immunogenic cell death. Radiotherapy also induces massive release of tumor antigens, accompanied by danger signals known to trigger the immune system. In REPORT, we explore the ability of PD1 blockade to harness this immune response. ALICE is a randomized, double-blind, placebo-controlled phase IIb study evaluating the efficacy and safety of atezolizumab when combined with immunogenic chemotherapy in subjects with metastatic TNBC. A total of 75 patients will be included and randomized 2:3, as follows: • Arm A (n=30): Chemo (Caelyx + cyclophosphamide) + placebo • Arm B (n=45): Chemo (Caelyx + cyclophosphamide) + atezolizumab Primary objectives: 1) Progression-free survival (when 90% have progressed) 2) Toxicity Secondary objectives: 3) Assessment of clinical response: Overall tumor response rate (ORR), duration of response (DR), durable tumor response rate (DRR; >6 months), overall survival (OS) 4) Immunological response 5) Health-related quality of life 6) Biomarkers for clinical response, toxicity and immune response 7) Characterization of tumor evolution and changes in immunological milieu Progress: Patient inclusion started August 2017. We have to date included 17 patients in the ALICE-trial. We have now opened new centers in Denmark (Copenhagen, Vejle) and at St Olav, and expect an improved enrollment rate from Jan 2019. REPORT is a singel-arm, open label phase I/II study evaluating the safety and efficacy of nivolumab when combined with re-irradiation in 20 patients with recurrent HNSCC. Primary objectives: 1) Safety and tolerability of nivolumab administered concomitant with re-irradiation in HNSCC 2) To determine a safe dose of nivolumab when administered concomitant with re-irradiation Secondary objectives: 3) Progression-free survival after 12 months 4) To evaluate tumor response (ORR, DOR, DRR) and overall survival 5) Immunological response 6) Biomarkers for clinical response, toxicity and immune response 7) To investigate tumor evolution and changes in microenvironment Progress: Patient inclusion started August 2017. We have to date included 8 patients in the REPORT trial. The ALICE and REPORT trials include cutting edge translational sub-projects, building on extensive collection of biopsies and peripheral blood samples. Through a carefully assembled team, we are able to address a series of important challenges within the field. The methods for investigating biomarkers and immune responses are being established. This includes CyTOF, flow cytometry, gene profiling, IHC, multimers.
2017
Immunotherapy represents an important novel development within cancer treatment. In particular, antibodies blocking the immune checkpoints show remarkable clinical activity. In the present project, we conduct two clinical trials, investigating novel strategies for combing checkpoint inhibitors with immunogenic chemo- or radiotherapy.Immunotherapy with antibodies blocking the checkpoint PD-1/PD-L1 show remarkable clinical activity against several cancer forms. These drugs enhance the patient´s anti-tumor immune response. However, in most cancer forms, only a minority of patients respond. In the present project, we investigate novel strategies for combing checkpoint inhibitors with chemo-and radiotherapy. We have in August 2017 started two clinical trials: • ALICE: A randomized placebo-controlled phase II study evaluating PD-L1 blockade combined with immunogenic chemotherapy in patients with metastatic triple negative breast cancer (mTNBC) • REPORT: REirradiation and PD-1 blockade On Recurrent head and neck squamous cell carcinoma (HNSCC) Intriguingly, the host immune response is strongly predictive for the effect of chemotherapy in mTNBC. In the ALICE trial, we aim at releasing the brake on the immune response by combining PD1/PD-L1 blockade with selected chemotherapy known to induce immunogenic cell death. Radiotherapy also induces massive release of tumor antigens, accompanied by danger signals known to trigger the immune system. In REPORT, we explore the ability of PD1 blockade to harness this immune response. ALICE is a randomized, double-blind, placebo-controlled phase IIb study evaluating the efficacy and safety of atezolizumab when combined with immunogenic chemotherapy in subjects with metastatic TNBC. A total of 75 patients will be included and randomized 2:3, as follows: • Arm A (n=30): Chemo (Caelyx + cyclophosphamide) + placebo • Arm B (n=45): Chemo (Caelyx + cyclophosphamide) + atezolizumab Primary objectives: 1) Progression-free survival (when 90% have progressed) 2) Toxicity Secondary objectives: 3) Assessment of clinical response: Overall tumor response rate (ORR), duration of response (DR), durable tumor response rate (DRR; >6 months), overall survival (OS) 4) Immunological response 5) Health-related quality of life 6) Biomarkers for clinical response, toxicity and immune response 7) Characterization of tumor evolution and changes in immunological milieu Progress: Patient inclusion started August 2017. We have to date included 8 patients in the ALICE-trial. The biobanking has been established. REPORT is a singel-arm, open label phase I/II study evaluating the safety and efficacy of nivolumab when combined with re-irradiation in 20 patients with recurrent HNSCC. Primary objectives: 1) Safety and tolerability of nivolumab administered concomitant with re-irradiation in HNSCC 2) To determine a safe dose of nivolumab when administered concomitant with re-irradiation Secondary objectives: 3) Progression-free survival after 12 months 4) To evaluate tumor response (ORR, DOR, DRR) and overall survival 5) Immunological response 6) Biomarkers for clinical response, toxicity and immune response 7) To investigate tumor evolution and changes in microenvironment Progress: Patient inclusion started August 2017. We have to date included 4 patients in the REPORT trial. The biobanking has been established. The ALICE and REPORT trials include cutting edge translational sub-projects, building on extensive collection of biopsies and peripheral blood samples. Through a carefully assembled team, we are able to address a series of important challenges within the field. The methods for investigating biomarkers and immune responses are being established. This includes CyTOF, flow cytometry, gene profiling, IHC, multimers.
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Jin Y, Lorvik KB, Jin Y, Beck C, Sike A, Persiconi I, Kvaløy E, Saatcioglu F, Dunn C, Kyte JA

Development of STEAP1 targeting chimeric antigen receptor for adoptive cell therapy against cancer.

Mol Ther Oncolytics 2022 Sep 15;26():189. Epub 2022 jun 22

PMID: 35860008

Kyte JA

Strategies for Improving the Efficacy of CAR T Cells in Solid Cancers.

Cancers (Basel) 2022 Jan 23;14(3). Epub 2022 jan 23

PMID: 35158839

Aamdal E, Skovlund E, Jacobsen KD, Straume O, Kersten C, Herlofsen O, Karlsen J, Hussain I, Amundsen A, Dalhaug A, Nyakas M, Hagene KT, Holmsen K, Aamdal S, Kaasa S, Guren TK, Kyte JA

Health-related quality of life in patients with advanced melanoma treated with ipilimumab: prognostic implications and changes during treatment.

ESMO Open 2022 Oct;7(5):100588. Epub 2022 sep 16

PMID: 36116420

Kyte JA, Andresen NK, Russnes HG, Fretland SØ, Falk RS, Lingjærde OC, Naume B

ICON: a randomized phase IIb study evaluating immunogenic chemotherapy combined with ipilimumab and nivolumab in patients with metastatic hormone receptor positive breast cancer.

J Transl Med 2020 07 03;18(1):269. Epub 2020 jul 3

PMID: 32620163

Kyte JA, Røssevold A, Falk RS, Naume B

ALICE: a randomized placebo-controlled phase II study evaluating atezolizumab combined with immunogenic chemotherapy in patients with metastatic triple-negative breast cancer.

J Transl Med 2020 06 23;18(1):252. Epub 2020 jun 23

PMID: 32576225

Brunsvig PF, Guren TK, Nyakas M, Steinfeldt-Reisse CH, Rasch W, Kyte JA, Juul HV, Aamdal S, Gaudernack G, Inderberg EM

Long-Term Outcomes of a Phase I Study With UV1, a Second Generation Telomerase Based Vaccine, in Patients With Advanced Non-Small Cell Lung Cancer.

Front Immunol 2020;11():572172. Epub 2020 nov 26

PMID: 33324397

Casey NP, Kyte JA, Fujiwara H

Use of RNA Interference with TCR Transfer to Enhance Safety and Efficiency.

Methods Mol Biol 2020;2115():327-349.

PMID: 32006409

Tekpli X, Lien T, Røssevold AH, Nebdal D, Borgen E, Ohnstad HO, Kyte JA, Vallon-Christersson J, Fongaard M, Due EU, Svartdal LG, Sveli MAT, Garred Ø, , Frigessi A, Sahlberg KK, Sørlie T, Russnes HG, Naume B, Kristensen VN

An independent poor-prognosis subtype of breast cancer defined by a distinct tumor immune microenvironment.

Nat Commun 2019 Dec 03;10(1):5499. Epub 2019 des 3

PMID: 31796750

Kyte JA, Fåne A, Pule M, Gaudernack G

Transient redirection of T cells for adoptive cell therapy with telomerase-specific T helper cell receptors isolated from long term survivors after cancer vaccination.

Oncoimmunology 2019;8(4):e1565236. Epub 2019 jan 19

PMID: 30906659

Doktorgrader
Andreas Hagen Røssevold

Immunotherapy and immunological biomarkers in breast cancer

Disputert:
februar 2024
Hovedveileder:
Jon Amund Kyte
Elin Aamdal

Treating metastatic melanoma with ipilimumab

Disputert:
juni 2022
Hovedveileder:
Jon Amund Kyte
Deltagere
  • Nikolai Andresen Doktorgradsstipendiat (annen finansiering)
  • Tormod Kyrre Guren Prosjektdeltaker
  • Elin Aamdal Doktorgradsstipendiat (annen finansiering)
  • Yixin Jin Postdoktorstipendiat (annen finansiering)
  • Kristina Berg Lorvik Postdoktorstipendiat (annen finansiering)
  • Claire Dunn Postdoktorstipendiat (annen finansiering)
  • Sudhir Chauhan Prosjektdeltaker
  • Sunil Raj Prosjektdeltaker
  • Christina Bjerre Prosjektdeltaker
  • Esmail Dorraji Postdoktorstipendiat (finansiert av denne bevilgning)
  • Andreas Hagen Røssevold Doktorgradsstipendiat (annen finansiering)
  • Ragnhild Sørum Falk Prosjektdeltaker
  • Vessela N. Kristensen Prosjektdeltaker
  • Hege Elisabeth Giercksky Russnes Prosjektdeltaker
  • Bjørnar Gilje Prosjektdeltaker
  • Åse Bratland Prosjektdeltaker
  • Bjørn Naume Prosjektdeltaker
  • Jon Amund Kyte Prosjektleder

eRapport er utarbeidet av Sølvi Lerfald og Reidar Thorstensen, Regionalt kompetansesenter for klinisk forskning, Helse Vest RHF, og videreutvikles av de fire RHF-ene i fellesskap, med støtte fra Helse Vest IKT

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