Stereotactic ablative body radiotherapy (SABR) combined with immunotherapy (L19-IL2) versus standard of care in stage IV NSCLC patients, ImmunoSABR: a multicentre, randomised controlled open-label phase II trial

Lieverse, Ritsaert; Limbergen, Evert J. Van; Oberije, Cary; Troost, Esther G.C.; Hadrup, Sine Reker; Dingemans, Anne‐Marie C.; Hendriks, L.; Eckert, Franziska; Hiley, Crispin; Dooms, Christophe; Lievens, Yolande; Jong, Monique C. de; Bussink, Johan; Geets, Xavier; Valentini, Vincenzo; Elia, Giuliano; Neri, Dario; Billiet, Charlotte; Abdollahi, Amir; Pasquier, David; Boisselier, P.; Yaromina, Ala; Ruysscher, Dirk De; Dubois, Ludwig; Lambin, Philippe

doi:10.1186/s12885-020-07055-1

Cited by 37 publications

(31 citation statements)

References 71 publications

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“…These studies provide important information for the design of clinical trials, suggesting that IO should be combined concurrently with fRT or it should be administered shortly after ablative radiation doses, depending on the type of IO. The clinical translation of these results can be demonstrated by the recently started international multicentric randomized Phase 2 trial ImmunoSABR (NCT03705403), where L19–IL2 is combined with ablative radiation doses in a sequential manner [ 102 ].…”

Section: Window Of Opportunity To Achieve Synergy Between Radiothementioning

confidence: 99%

“…We have demonstrated in several preclinical studies the ability of RT to synergize with L19–IL2 and to induce durable systemic antitumor responses [ 96 , 97 , 149 ]. Our promising results prompted us to conduct clinical trials investigating the toxicity, which is deemed safe or tolerable, and therapeutic efficacy of this combination [ 102 , 150 ] (NCT02735850, NCT03705403, NCT04604470).…”

Section: Immunotherapeutic Options and Conventional Radiotherapymentioning

confidence: 99%

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Charged Particle and Conventional Radiotherapy: Current Implications as Partner for Immunotherapy

Marcus

Lieverse

Klein

et al. 2021

Cancers

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Radiotherapy (RT) has been shown to interfere with inflammatory signals and to enhance tumor immunogenicity via, e.g., immunogenic cell death, thereby potentially augmenting the therapeutic efficacy of immunotherapy. Conventional RT consists predominantly of high energy photon beams. Hypofractionated RT regimens administered, e.g., by stereotactic body radiation therapy (SBRT), are increasingly investigated in combination with cancer immunotherapy within clinical trials. Despite intensive preclinical studies, the optimal dose per fraction and dose schemes for elaboration of RT induced immunogenic potential remain inconclusive. Compared to the scenario of combined immune checkpoint inhibition (ICI) and RT, multimodal therapies utilizing other immunotherapy principles such as adoptive transfer of immune cells, vaccination strategies, targeted immune-cytokines and agonists are underrepresented in both preclinical and clinical settings. Despite the clinical success of ICI and RT combination, e.g., prolonging overall survival in locally advanced lung cancer, curative outcomes are still not achieved for most cancer entities studied. Charged particle RT (PRT) has gained interest as it may enhance tumor immunogenicity compared to conventional RT due to its unique biological and physical properties. However, whether PRT in combination with immune therapy will elicit superior antitumor effects both locally and systemically needs to be further investigated. In this review, the immunological effects of RT in the tumor microenvironment are summarized to understand their implications for immunotherapy combinations. Attention will be given to the various immunotherapeutic interventions that have been co-administered with RT so far. Furthermore, the theoretical basis and first evidences supporting a favorable immunogenicity profile of PRT will be examined.

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Section: Window Of Opportunity To Achieve Synergy Between Radiothementioning

confidence: 99%

Section: Immunotherapeutic Options and Conventional Radiotherapymentioning

confidence: 99%

Charged Particle and Conventional Radiotherapy: Current Implications as Partner for Immunotherapy

Marcus

Lieverse

Klein

et al. 2021

Cancers

Self Cite

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“…A clinical phase II study recently demonstrated that hu14.18-IL2 given in combination with GM-CSF and the differentiation inducing agent isotretinoin is safe and tolerable, and showed anti-tumor activity in patients with relapsed/ refractory neuroblastoma (135). Several other IL2-antibody fusions have advanced to clinical trials, including huKS-IL2 (136), NHS-IL2 (128) and L19-IL2 (137). The combination of RT (5 x 4 Gy) followed by NHS-IL2 after first-line chemotherapy in metastatic non-small cell lung cancer (NSCLC) patients was well tolerated (128).…”

Section: Future Perspective: Multifunctional Antibody Development and In Situ Tumor Ablationmentioning

confidence: 99%

Immune Modulation Plus Tumor Ablation: Adjuvants and Antibodies to Prime and Boost Anti-Tumor Immunity In Situ

et al. 2021

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In situ tumor ablation techniques, like radiotherapy, cryo- and heat-based thermal ablation are successfully applied in oncology for local destruction of tumor masses. Although diverse in technology and mechanism of inducing cell death, ablative techniques share one key feature: they generate tumor debris which remains in situ. This tumor debris functions as an unbiased source of tumor antigens available to the immune system and has led to the concept of in situ cancer vaccination. Most studies, however, report generally modest tumor-directed immune responses following local tumor ablation as stand-alone treatment. Tumors have evolved mechanisms to create an immunosuppressive tumor microenvironment (TME), parts of which may admix with the antigen depot. Provision of immune stimuli, as well as approaches that counteract the immunosuppressive TME, have shown to be key to boost ablation-induced anti-tumor immunity. Recent advances in protein engineering have yielded novel multifunctional antibody formats. These multifunctional antibodies can provide a combination of distinct effector functions or allow for delivery of immunomodulators specifically to the relevant locations, thereby mitigating potential toxic side effects. This review provides an update on immune activation strategies that have been tested to act in concert with tumor debris to achieve in situ cancer vaccination. We further provide a rationale for multifunctional antibody formats to be applied together with in situ ablation to boost anti-tumor immunity for local and systemic tumor control.

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“…This concept is related to the wider definition of “oligometastatic” disease (“oligo” = “few”) that refers to a limited number of metastases and/or metastatic sites characterized by a more indolent behavior than a polymetastatic disease [ 5 , 6 ]. Although there is no consensus on the appropriate cut off to define the oligometastatic state, generally up to 3–5 lesions in 1–3 organs are defined in international guidelines and are commonly accepted [ 7 , 8 , 9 ].…”

Section: Definition and Biology Of Oligoprogression In Ansclcmentioning

confidence: 99%

Beyond First-Line Immunotherapy: Potential Therapeutic Strategies Based on Different Pattern Progressions: Oligo and Systemic Progression

Prelaj

Pircher

Massa

et al. 2021

Cancers

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First-line immune-checkpoint inhibitor (ICI)-based therapy has deeply changed the treatment landscape and prognosis in advanced non-small cell lung cancer (aNSCLC) patients with no targetable alterations. Nonetheless, a percentage of patients progressed on ICI as monotherapy or combinations. Open questions remain on patients’ selection, the identification of biomarkers of primary resistance to immunotherapy and the treatment strategies to overcome secondary resistance to first-line immunotherapy. Local ablative approaches are the main therapeutic strategies in oligoprogressive disease, and their role is emerging in patients treated with immunotherapy. Many therapeutic strategies can be adapted in aNSCLC patients with systemic progression to personalize the treatment approach according to re-characterization of the tumors, previous ICI response, and type of progression. This review’s aim is to highlight and discuss the current and potential therapeutic approaches beyond first-line ICI-based therapy in aNSCLC patients based on the pattern of disease progression (oligoprogression versus systemic progression).

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Stereotactic ablative body radiotherapy (SABR) combined with immunotherapy (L19-IL2) versus standard of care in stage IV NSCLC patients, ImmunoSABR: a multicentre, randomised controlled open-label phase II trial

Cited by 37 publications

References 71 publications

Charged Particle and Conventional Radiotherapy: Current Implications as Partner for Immunotherapy

Charged Particle and Conventional Radiotherapy: Current Implications as Partner for Immunotherapy

Immune Modulation Plus Tumor Ablation: Adjuvants and Antibodies to Prime and Boost Anti-Tumor Immunity In Situ

Beyond First-Line Immunotherapy: Potential Therapeutic Strategies Based on Different Pattern Progressions: Oligo and Systemic Progression

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