2020 Areas of Interest for Pembrolizumab Bladder Cancer

2020 Areas of Interest for Pembrolizumab Bladder Cancer Early Stage:
  • Pembrolizumab in combination with novel agents/strategies (e.g. intravesical drugs/devices, other systemic agents, alternative surgical techniques/technology, etc.) for the treatment of NMIBC
  • Novel strategies for bladder preservation with pembrolizumab combinations
  • Studies that include objectives to investigate biological mechanisms of pembrolizumab response or resistance Late Stage:
  • Pembrolizumab combinations in the perioperative setting for MIBC (i.e. olaparib, chemotherapy, targeted therapy, novel agents, etc.)
  • Studies that include objectives to investigate biological mechanisms of pembrolizumab response or resistance
  • Novel combinations in PD-1/PD-L1 refractory population Breast Cancer
  • Use of pembrolizumab after progression on prior PD-1/L1 inhibitor or other IO
  • Novel pembrolizumab combinations, such as with other IOs, AKTi, ADCs, TKIs, etc.
  • Studies in well-established clinically relevant biomarker subsets Colorectal Cancer
  • Pembrolizumab novel* combinations for metastatic MSI-H or MSS CRC with strong scientific/pre-clinical rationale, including but not limited to combination partners with immune or metabolic targets *excluding chemo-only combinations, RT only combinations, or VEGF only combinations
  • GI/ Gastric Pancreatic Cancer
  • Pembrolizumab combinations, including standard of care, chemotherapy, or novel agents, with strong biological and clinical rationale and have established safety
  • Incorporation of novel biomarker strategies are desirable with higher interest in metastatic disease. Innovative trial design for earlier stages of disease will be considered.
  • Pembrolizumab in combination with olaparib or novel agents, with higher interest in metastatic disease. Esophageal and gastric Cancer (Highest interest in PD-L1–negative and MSS tumors)
  • Pembrolizumab combination therapy, including novel agents, with strong biological and clinical rationale that potentially address resistance pathways and have established safety
  • Pembrolizumab in combination with olaparib or lenvatinib (excluding chemoradiation approaches)
  • Concurrent chemoradiation strategies
  • Incorporation of novel biomarker strategies for patient selection
  • Exploration of drug sequencing with pembrolizumab for resensitization Gynaecological Cancers Ovarian cancer
  • Combination therapies in recurrent ovarian cancer
  • Particular interest in post IO / post PARPi
  • Rare histologies Cervical cancer
  • Combination therapies in recurrent cervical cancer
  • Post PD1
  • Rare histologies Endometrial cancer
  • Combination therapies in recurrent endometrial cancer
  • Novel pembrolizumab combinations
  • Rare histologies Vulvar cancer
  • Combination therapies
  • Hematological Malignancies Classical Hodgkin’s Lymphoma
  • Frontline pembrolizumab as monotherapy or in combinations (sequential or concurrent) in young adults, adults and elderly with Hodgkin lymphoma
  • Pembrolizumab monotherapy/combinations as maintenance (consolidative therapy) post Autologous Stem Cell Transplant
  • Pembrolizumab in novel combinations in relapsed/ refractory setting Non-Hodgkin’s Lymphoma
  • Novel pembrolizumab containing combinations with chemotherapy or nonchemotherapy agents (including cell-based therapies) in frontline and relapsed/ refractory settings in Diffuse Large B-Cell Lymphoma, Primary Mediastinal B-Cell Lymphoma, and Follicular Lymphoma Multiple Myeloma
  • Novel pembrolizumab containing (no IMiD or carfilzomib) combinations with focus on bispecific Antibodies, Antibody-Drug Conjugates, or cell-based therapies in the relapsed/refractory setting Head & Neck Cancers HNSCC
  • Novel combinations in HNSCC
  • Novel combinations in sinonasal carcinomas, including adjuvant therapy
  • Larynx preservation studies
  • Pembrolizumab + olaparib in platinum-sensitive HNSCC
  • Pembrolizumab + chemo or novel combinations in platinum-refractory population
  • Pembrolizumab + chemo or novel combinations in PD1-refractory population NPC
  • Pembrolizumab + chemo or novel combinations in platinum-refractory population
  • Pembrolizumab + chemo or novel combinations in PD1-refractory population
  • Combinations with pembrolizumab in curative setting, including CCRT Salivary Gland and Thyroid Carcinomas
  • Novel combinations in salivary gland and thyroid carcinomas, including adjuvant therapy in inoperable salivary gland carcinoma Cutaneous SCC
  • Pembrolizumab +/- other agents in long term stable immunocompromised cSCC (controlled HIV)
  • Neoadjuvant therapy in cutaneous SCC
  • Hepatobiliary Cancers Hepatocellular Cancers
  • Neoadjuvant/window of opportunity studies in early stages of HCC
  • I/O-I/O combinations with pembrolizumab in advanced disease
  • Strategies to improve pembrolizumab efficacy in advanced and early stages of disease
  • Strategies to re-sensitize after PD on pembrolizumab with addition of new agents Biliary Cancers
  • Pembrolizumab combinations in preselected molecular subsets (including but not limited to IDH, FGFR, HER-2)
  • Neoadjuvant/window of opportunity studies in early stages of biliary cancer
  • I/O-I/O combinations with pembrolizumab in advanced disease
  • Strategies to improve pembrolizumab efficacy in advanced and early stages of disease Thoracic Malignancies NSCLC
  • Novel neoadjuvant combinations
  • Novel combinations in IO pre-exposed patients
  • I/O, I/O combinations
  • Overcoming specific mechanism of resistance (e.g. LKB-1)
  • Novel combinations in mutation driven patients
  • VEGFRi and EGFRmut
  • Non-EGFRmut tumors
  • Novel TKI +pembro for non-EGFR, non-ALK mutation driven patients
  • Novel combinations in special populations (brain mets, PS=2, autoimmune disorders)
  • VEGFRi combination in patients with brain metastases SCLC
  • Novel combinations in 1L
  • Determining mechanisms to improve response and outcomes in 1L based on biology of disease
  • Determining mechanisms of resistance
  • Novel combinations in I/O pre-exposed patients Mesothelioma
  • Novel combination in 1L and in 2L
  • Determining mechanisms to improve response and outcomes
  • Novel combinations in I/O pre-exposed patients
  • Melanoma
  • Novel combinations for patients with high-risk melanoma, with emphasis on those with a detailed/described mechanism. Examples include, but are not limited to:
  • PD-1/CTLA-4 resistant/refractory patients
  • Mucosal/Acral melanoma
  • Uveal melanoma
  • Brain metastases
  • Neoadjuvant/adjuvant therapy
  • Real world data on treatment patterns and outcomes in patients excluded from clinical trials Merkel Cell Carcinoma
  • Novel combinations in Merkel cell carcinoma (including neoadjuvant) Innovative Strategies
  • Pembrolizumab-based combinations in advanced cancers with a high unmet medical need. Lenvatinib + pembrolizumab or olaparib + pembrolizumab combinations are encouraged. Proposals with a translational rationale/evidence or component (e.g. neoadjuvant) are highly encouraged.
  • Prostate Cancer
  • Neo-adjuvant or adjuvant studies of pembrolizumab as monotherapy and in combination
  • Combinations of interest include, but not limited to TGFß antagonists, CDK-12 mutation, targeted radiation assets (e.g. PSMA-Actinium, and Thorium), olaparib, novel immune checkpoint agents, VISTA, and nano-particle delivery therapeutics
  • Primary disease, high risk after primary definitive therapy and locally advanced/metastatic disease
  • Combinations with oncolytic viral assets, radiation, PARP inhibition, CDK-12 mutation positive patient population etc.
  • Novel combinations of pembrolizumab for small cell / neuroendocrine-like differentiated disease
  • Studies that include objectives to investigate biological mechanisms of pembrolizumab response or resistance
  • Studies evaluating biochemical failure
  • Renal Cell Carcinoma
  • Pembrolizumab combinations with novel mechanisms of action
  • Combinations of interest include but not limited to metabolic pathways, epigenetic pathways, targeting of the myeloid compartment and other emerging immune and non-immune pathways
  • Pembrolizumab combination studies in patients with clear cell and non-clear cell histologies, who are treatment naïve and patients who received prior treatment (including IO and/or TKI).
  • Studies that include objectives to investigate biological mechanisms of pembrolizumab response or resistance Preclinical
  • Evaluation of PD-1 Pathway Mechanism of Action
  • Understand the mechanistic basis for response/resistance to anti-PD-1. There is particular interest in studies assessing:
  • Cell Types
  • Immune cells: B cells (investigation of the role of PD-1 signaling in the humoral response), gamma delta T cells, natural killer (NK) cells, antigen presenting cells, exhausted T cells
  • Associated cells: Fibroblast reticular cells (FRCs), cancer associated fibroblasts (CAFs)
  • Tumor cells: intrinsic mechanisms that provide sensitivity or resistance to PD-1 inhibitors
  • Pathways
  • Angiogenesis, hypoxia, epithelial-mesenchymal transition (EMT), antigen presentation and machinery
  • Pembrolizumab combinations
  • Identify mechanisms of action associated with reported clinical response to anti-PD-1 combination treatment (reverse translational studies)
  • Targeting the tumor-stromal-immune cell axis:
  • Identify mechanisms of action that modulate the tumor stroma
  • Identify mechanisms of action that modulate vasculature to enhance immune cell trafficking
  • Mechanical and biophysical aspects of the tumor micro-environment
  • Evaluate the contribution of tumor intrinsic pathways to immune escape
  • Identify mechanisms of action that modulate immune suppressive cell function natural killer (NK) cells, B cells (including tumor resident B cells), myeloid cells (MDSCs, DCs, TAMs)
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