Publications by authors named "Champiat S"

Article Synopsis
  • Tarlatamab, an immunotherapy targeting delta-like ligand 3, shows promising anticancer effects in small cell lung cancer (SCLC) based on the DeLLphi-300 and DeLLphi-301 trials, with manageable safety profiles.
  • In the extended follow-up of DeLLphi-300, the overall response rate was 25%, with a median duration of response of 11.2 months and a median overall survival of 17.5 months across 152 patients.
  • Among those receiving a specific dose regimen (10 mg every two weeks), 35.3% experienced a response, and notable intracranial tumor shrinkage was found in patients with existing brain lesions, highlighting tarlatam
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  • Patients with advanced tumors in phase I trials often have strong treatment hopes but limited options; local ablative stereotactic radiation therapy (SRT) can help manage disease progression when oligoprogressive resistance occurs.* -
  • A study analyzed 42 patients receiving SRT for oligoprogressive lesions, finding that SRT significantly extended progression-free survival (7.1 months) and time to the next treatment (12.8 months), with no severe toxicities reported.* -
  • The findings suggest that tumor characteristics, like aggressiveness and clonal diversity, can help distinguish between patients needing different management strategies after SRT, potentially enhancing treatment outcomes.*
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  • Antibody-drug conjugates (ADCs) are a promising cancer treatment that combines targeted monoclonal antibodies with potent drugs, relying on the expression levels of target proteins in cancer cells for effectiveness.
  • This review analyzes clinical trial results from January 2019 to May 2023, highlighting approved ADCs that show efficacy even in tumors with low levels of target protein expression.
  • It emphasizes the challenges in accurately assessing target protein levels due to inconsistent evaluation methods and the complexity of ADC behavior in the body, advocating for standardized approaches to improve future ADC therapies.
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Purpose: With liquid biopsy's widespread adoption in oncology, an increased number of clonal hematopoiesis-associated mutations (CHm) have been identified in patients with solid tumors. However, its impact on patient outcomes remains unclear. This study aimed to analyze and describe CHm in a cohort of phase I patients.

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T-cell engagers (TCE) are cancer immunotherapies that have recently demonstrated meaningful benefit for patients with hematological malignancies and solid tumors. The anticipated widespread use of T cell engagers poses implementation challenges and highlights the need for guidance to anticipate, mitigate, and manage adverse events. By mobilizing T-cells directly at the contact of tumor cells, TCE mount an obligatory and immediate anti-tumor immune response that could result in diverse reactions and adverse events.

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Chemotherapy associated with Immune Checkpoint Inhibitors is currently the standard of care in several tumor indications. This combination approach improves progression free survival (PFS), overall survival (OS) and complete pathological response (pCR) in several cancer types both in the early and metastatic approaches. However, the distinct spectrum of toxicities between cytotoxic side effects and immune related adverse events (irAEs) with similar clinical presentations and different management strategies remains a challenge in daily practice for healthcare professionals.

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Purpose: In this study, we report the results from the esophageal squamous cell carcinoma (SCC) cohort of a phase II, noncomparative, basket study evaluating the antitumor activity and safety of fibroblast activation protein-IL2 variant (FAP-IL2v) plus atezolizumab in patients with advanced/metastatic solid tumors (NCT03386721).

Patients And Methods: Eligible patients had an Eastern Cooperative Oncology Group performance status of 0 to 1; measurable metastatic, persistent, or recurrent esophageal SCC; progression on ≥1 prior therapy; and were checkpoint inhibitor-naïve. Patients received FAP-IL2v 10 mg plus atezolizumab 1,200 mg intravenously every 3 weeks, or FAP-IL2v weekly for 4 weeks and then every 2 weeks plus atezolizumab 840 mg intravenously every 2 weeks.

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Patients with advanced cancer, previously treated with immune checkpoint blockade therapy, may retain residual treatment when undergoing the initial infusion of experimental monotherapy in phase 1 clinical trials. ANV419, an antibody-cytokine fusion protein, combines interleukin-2 (IL-2) with an anti-IL-2 monoclonal antibody, aiming to stimulate the expansion of CD8 T and natural killer lymphocytes while restricting regulatory T lymphocytes. In the recent publication of the phase 1 dose escalation study of ANV419, a notable gap exists in detailed information regarding patients' prior antitumoral treatments, specifically programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) targeted monoclonal antibodies.

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More than half of cancer cases occur in patients aged 65 years or older. The efficacy and safety of antibody drug conjugates (ADCs) in older patients remains an unclear subject as available evidence is limited. Geriatric population is underrepresented in clinical trials.

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Cancer treatments have recently shifted from broad-spectrum cytotoxic therapies to more focused treatments, maximizing anticancerous activity while reducing toxicity to healthy cells. These modern anticancer therapies (MATs) encompass a wide range of innovative molecules that include immune checkpoint inhibitors and other targeted anticancer therapies, comprising antibody drug conjugates and inhibitors of signal transduction. Some MATs are associated with ocular surface adverse events that can cause severe discomfort and even lead to loss of vision.

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Background: Immune-checkpoint inhibitor (ICI) hepatitis, which does not improve with steroids and requires additional immunosuppressant, is defined as steroid-refractory ICI hepatitis. The outcome of patients with steroid-refractory ICI hepatitis remains poorly determined. Herein, we investigated the incidence, clinical features, and outcome of patients treated with second-line immunosuppressant for steroid-refractory ICI hepatitis.

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Background: Cytokine release syndrome (CRS) is a common adverse event of CAR T cell or bispecific antibody (bsAb) therapy. Anti-IL6/IL6R drugs are used in the management of auto-immune diseases. Some reports showed increased risk of bacterial infection in this context.

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Background: Phase I trials historically involved heavily pretreated patients (pts) with no more effective therapeutic options available and with poor expected outcomes. There are scare data regarding profile and outcomes of pts enrolled into modern phase I trials. Here, we sought to provide an overview of pts' profile and outcome into phase I trials at Gustave Roussy (GR).

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Purpose Of Review: This review presents the rationale for intratumoral immunotherapy, technical considerations and safety. Clinical results from the latest trials are provided and discussed.

Recent Findings: Intratumoral immunotherapy is feasible and safe in a wide range of cancer histologies and locations, including lung and liver.

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Immune-related adverse events (irAEs) associated with immune checkpoint inhibitor (ICI) therapy may vary substantially in their clinical presentation, including natural history, outcomes to treatment, and patterns. The application of clinical guidelines for irAE management can be challenging for practitioners due to a lack of common or consistently applied terminology. Furthermore, given the growing body of clinical experience and published data on irAEs, there is a greater appreciation for the heterogeneous natural histories, responses to treatment, and patterns of these toxicities, which is not currently reflected in irAE guidelines.

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Background: The phase I first-in-human study ENGAGE-1 evaluated the humanized IgG1 OX40 agonistic monoclonal antibody GSK3174998 alone (Part 1 (P1)) or in combination with pembrolizumab (Part 2 (P2)) in patients with advanced solid tumors.

Methods: GSK3174998 (0.003-10 mg/kg) ± pembrolizumab (200 mg) was administered intravenously every 3 weeks using a continuous reassessment method for dose escalation.

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Hyperprogression is a paradoxical cancer acceleration observed in a minority of patients upon immunotherapy. In this issue of Cancer Cell, Li et al demonstrate that hyperprogressive tumors upregulate the Wnt/β-catenin pathway. This activation was subsequent to an oncogenic FGF2-mediated autocrine loop generated by the IFNγ released by CD8 T cells upon PD-1/PD-L1 blockade.

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Purpose: The objective of the study is to propose the immunotherapy progression decision (iPD) score, a practical tool based on patient features that are available at the first evaluation of immunotherapy treatment, to help oncologists decide whether to continue the treatment or switch rapidly to another therapeutic line when facing a progressive disease patient at the first evaluation.

Experimental Design: This retrospective study included 107 patients with progressive disease at first evaluation according to RECIST 1.1.

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Article Synopsis
  • Tarlatamab (AMG 757) is a new treatment for small-cell lung cancer (SCLC) that targets DLL3 and CD3, leading to tumor destruction through T-cell activation.
  • In a phase I study involving 107 patients with relapsed/refractory SCLC, results showed a 23.4% objective response rate, with manageable safety issues and a median duration of response of 12.3 months.
  • The findings indicate that tarlatamab may be a promising treatment option for heavily pretreated SCLC patients, warranting further research, especially in patients with higher DLL3 expression.
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  • Recent studies indicate that combining cancer immunotherapy drugs can improve survival rates for patients with advanced mesothelioma who respond to treatment.
  • A trial involving pembrolizumab and nintedanib revealed that patients resistant to these treatments had active immune responses, but also exhibited genetic alterations linked to inflammation and immune suppression in their tumors.
  • Findings suggest that understanding the specific tumor biology of mesothelioma could lead to more effective, tailored combination therapies for better patient outcomes.
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Background: Generalised oedema was occasionally reported associated with immune checkpoint inhibitors (ICPIs). The purpose of this study is to investigate immune-related generalised oedema (ir-GE) drug related to ICPI, through frequency, clinical and pathological characteristics, and patient's outcome.

Patients And Methods: Objectives of the study were to report on ir-GE associated with ICPI to define frequency, associated signs and symptoms, pathological characteristics, severity, and response to corticosteroids.

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Introduction: Association of high body mass index (BMI) with longer survival has been reported in patients on immune checkpoint inhibitors (ICIs), but results are inconsistent. This 'obesity paradox' is potentially confounded by the effects of BMI change over time and of skeletal muscle depletion.

Methods: We conducted a secondary analysis of a prospective cohort, including consecutive patients receiving ICI treatment for melanoma (n = 411) and non-small cell lung cancer (NSCLC) (n = 389) in routine care.

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Article Synopsis
  • Anti-PD-(L)1 immunotherapies show promise in improving survival rates for various cancers, but they don't work for everyone, leading researchers to use machine learning to analyze patient data for better predictions of survival outcomes.
  • The study examined 33 baseline medical variables from 695 advanced cancer patients, creating a random forest model to identify factors that significantly affect overall survival when treated with anti-PD-(L)1 therapies versus other treatments.
  • Key findings revealed that high levels of serum lactate dehydrogenase (LDH) and liver metastases predicted poor survival rates; patients with these traits experienced significantly shorter overall survival times, indicating the need for better patient stratification in clinical trials.
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