Precision Medicine in Oncology®

Bispecific antibodies have become an interesting new class of agents in the lung cancer pipeline, most recently with the developments of amivantamab-vmjw, zenocutuzumab, and tarlatamab.

Multicancer early detection tests yielded high specificity and accuracy in predicting cancer signal origin and identified cancer signals in multiple tumor types.

The FDA has approved the FoundationOne Liquid CDx for use as a companion diagnostic to assist in the identification of patients with metastatic non–small cell lung cancer whose tumors harbor MET exon 14 skipping mutations and who could derive benefit from treatment with capmatinib.

The lead novel candidate, the WEE1 inhibitor adavosertib, has been tested in more than 50 completed or ongoing clinical studies but has yet to proceed to a phase 3 trial despite showing promising safety and efficacy as monotherapy and in combination with a range of other cancer therapies.

During the past decade, a growing number of PD-1/PD-L1 inhibitors gained FDA approval to treat a wide range of cancer types. Their stimulatory counterparts also emerged as sought-after anticancer targets but have proved much more challenging to manipulate therapeutically.

The FDA has approved FoundationOne CDx for use as a companion diagnostic for brigatinib, which was approved for the treatment of adult patients with ALK-positive, metastatic non–small cell lung cancer.

NRG1 fusions, which are often first detected by RNA-based sequencing, confer a more molecularly, pathologically, and clinically diverse subtype of lung cancer compared with historical hypotheses.

Next-generation sequencing plays a critical role in the diagnosis of patients with myeloid malignancies, but it also plays a necessary role in the identification of passenger mutations and subclonal events that go beyond founding drivers.

Streamlined processes afforded by in-house genomic testing have the potential to provide clinical, collaborative, and financial benefits.

Alison Schram, MD, discusses the results of the phase 1/2 eNRGy trial, which were presented during the 2021 ASCO Annual Meeting, in NRG1 fusion–positive solid tumors.

Several distinct subgroups have been identified within the myelodysplastic syndrome genomic landscape and have notable clinical features and discrete evolution patterns that provide proof of concept for next-generation disease classification and prognosis.

Dual blockade of the RAF/MEK and FAK pathways presents an opportunity for investigators to enhance and expand the number of patients with recurrent low-grade serous ovarian cancer who can benefit from targeted therapies.

Multiple FDA approvals and an increasing number of clinical trials examining molecular target–based therapeutics, including second- or even third-generation drugs against a well-defined target, present an ever-widening array of drugs for routine cancer care based on the discovery of specific molecular targets within the tumor or within the germline.

Among the pioneering targets for antibody therapy was CD20, the pursuit of which ultimately led to the first FDA-approved mAb for cancer therapy, rituximab, and defined a new era in the management of B-cell malignancies.

Kaiku Health has announced that they are partnering with the global healthcare company Novartis to develop a digital patient monitoring and management system specifically for patients with melanoma who are receiving BRAF/MEK combination therapies.

In an effort to build on the efficacy demonstrated with ruxolitinib, investigators are evaluating combination therapies—specifically the dual inhibition of the JAK-STAT and BET pathways using pelabresib, a novel BET inhibitor.

Larotrectinib has demonstrated efficacious responses and disease control in patients with TRK fusion–positive central nervous system tumors.

Selumetinib did not elicit clinical activity in pediatric and young adult patients with refractory cancers who had actionable mutations in the RAS/RAF/MAPK1/2-ERK pathway.

The highly selective, central nervous system-active TRK inhibitor larotrectinib yielded promising response rates in patients with TRK fusion cancer, including in those with CNS metastases at baseline.

Pralsetinib demonstrated robust and durable anti-tumor activity, as well as a tolerable safety profile, in heavily pretreated patients with multiple RET fusion–positive advanced solid tumors.

Zenocutuzumab represents a promising novel targeted therapeutic option for patients with NRG1 fusion–positive cancers.

Sotorasib provided continued durable clinical benefit in patients with pretreated KRAS p.G12C–mutated non–small cell lung cancer.

The investigational SHP2 inhibitor TNO155 demonstrated encouraging safety and tolerability, and consistent evidence of SHP2 inhibition in patients with advanced solid tumors.

Melissa (Kah Poh) Loh, BMedSci, MBBCh, BAO, discusses the challenges of utilizing geriatric assessment in oncology and steps that the ACCC resources can provide to institutions that want to incorporate geriatric assessment into practice.

The FDA has approved the Guardant360 CDx assay as a companion diagnostic for tumor mutation profiling to identify patients with locally advanced or metastatic non–small cell lung cancer whose tumors harbor the KRAS G12C mutation and may derive benefit from sotorasib.

The FDA has approved infigratinib for the treatment of patients with previously treated locally advanced or metastatic cholangiocarcinoma harboring an FGFR2 fusion or rearrangement.

Artios Pharma, a company devoted to developing precision medicine–based treatments based on DNA damage response mechanisms, is entering into a global research collaboration with Novartis to develop next-generation DDR targets that will synergize with Novartis’ radioligand therapies.

Daiichi Sankyo Inc. is collaborating with Guardant Health Inc. to develop a companion diagnostic for fam-trastuzumab deruxtecan-nxki, which is being studied to treat patients with advanced metastatic HER2-mutated non‒small cell lung cancer.

Mark A. Socinski, MD, discusses the utility of circulating tumor DNA testing in lung cancer.

The FDA has granted approval to the Guardant360 CDx liquid biopsy assay as the first companion diagnostic for amivantamab-vmjw to determine which patients with locally advanced or metastatic non–small cell lung cancer harboring EGFR exon 20 insertion mutations may derive benefit from the agent after progressing on, or after, platinum-based chemotherapy.