EGFR exon 20 insertion driver mutations (Exon20ins) in non-small cell lung cancer (NSCLC) are insensitive to EGFR tyrosine kinase inhibitors (TKI). Amivantamab (JNJ-61186372), a bispecifi c antibody targeting EGFR-MET, has shown preclinical activity in TKI-sensitive EGFR-mutated NSCLC models and in an ongoing fi rst-inhuman study in patients with advanced NSCLC. However, the activity of amivantamab in Exon20ins-driven tumors has not yet been described. Ba/F3 cells and patient-derived cells/organoids/xenograft models harboring diverse Exon20ins were used to characterize the antitumor mechanism of amivantamab. Amivantamab inhibited proliferation by effectively downmodulating EGFR-MET levels and inducing immune-directed antitumor activity with increased IFN γ secretion in various models. Importantly, in vivo effi cacy of amivantamab was superior to cetuximab or poziotinib, an experimental Exon20ins-targeted TKI. Amivantamab produced robust tumor responses in two Exon20ins patients, highlighting the important translational nature of this preclinical work. These fi ndings provide mechanistic insight into the activity of amivantamab and support its continued clinical development in Exon20ins patients, an area of high unmet medical need. SIGNIFICANCE: Currently, there are no approved targeted therapies for EGFR Exon20ins-driven NSCLC. Preclinical data shown here, together with promising clinical activity in an ongoing phase I study, strongly support further clinical investigation of amivantamab in EGFR Exon20ins-driven NSCLC.

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The Internet of Things (IoT) is a rapidly emerging application space, poised to become the largest electronics market for the semiconductor industry. IoT devices are focused on sensing and actuating of our physical environment and have a nearly unlimited breadth of uses. In this paper, we explore the IoT application space and then identify two common challenges that exist across this space: ultra-low power operation and system design using modular, composable components. We survey recent low power techniques and discuss a low power bus that enables modular design. Finally, we conclude with three example ultra-low power, millimeter-scale IoT systems. IoT Application Space and ChallengesIoT devices are unique in that they are focused on physical interfaces, allowing them to sense and actuate the world around us. This is in contrast to previous computing platforms, such as desktop and handheld devices, which have primarily focused on human interfaces. These human interfaces require relatively large input and output devices and require the devices to be co-located with their users. In contrast, IoT devices receive input through sensors that are often highly miniaturized through MEMS technology and send out information through wired or wireless interfaces to mobile and cloud computers. This enables the placement of IoT devices in myrad new locations and applications where computing was previously absent. As a result, IoT presents the semiconductor industry with a market opportunity that may exceed that of all previous computing classes.The diversity of our physical environment results in a similarly diverse IoT application space that ranges from tiny implanted heart-rhythm monitors, to large, extremely long lifetime HVAC sensors, to sensors for oil reservoir diagnosis [1]. To categorize this wide application space we recognize four ontological properties that are critical in determining IoT device requirements: sensing modality, form factor (size), energy source / sensor lifetime, and connectivity. Table 1 lists example values for these properties. For instance, physical form factor can range from tiny millimeter size for implantable sensors to 10s of centimeters for infrastructure monitoring. Sensing modalities can include pressure, chemical, strain, and temperature, etc. In addition, the sensing modality can be characterized by measurement frequency and possible triggers , such as a timer, a detected event in the monitored value, or an external event such as a radio message.Similarly, communication connectivity is characterized by communication interval, distance, data rate/size, etc. Clearly the listed items are not exhaustive. Each property can take a very large number of possible values resulting in a highly varied application space. Some examples include 1) tiny sensors that measure temperature every 10 minutes using a secondary battery and harvesting with infrequent communication for studying Pika's in the Rocky mountains [2]; 2) continuous monitoring of brain activity in seizure patients with a contin...

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