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Oliver Maracic: Could Co-Targeting ALK with FAK/PYK2 Help Mitigate the High VTE Burden Seen in ALK with NSCLC
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Apr 30, 2026, 16:56

Oliver Maracic: Could Co-Targeting ALK with FAK/PYK2 Help Mitigate the High VTE Burden Seen in ALK with NSCLC

Oliver Maracic, Independent Oncology and Metabolic Disease Strategist, shared a post on LinkedIn about a recent article by Caroline Kamali published in JTO Clinical and Research Reports, adding:

“Could co-targeting ALK with FAK/PYK2 help mitigate the high VTE burden seen in ALK with NSCLC, arguably one of the highest-risk solid tumor settings for thrombosis?

The 36.1% VTE incidence (≈69% PE, many late-onset) in advanced ALK with NSCLC is striking. Risk factors such as adrenal metastases, leukocytosis, and anemia, point to a disease-specific thrombo-inflammatory biology that pure ALK TKIs have not addressed.

Importantly, prophylactic anticoagulation is not standard for ambulatory patients on targeted therapy (per NCCN/ASCO/ISTH; risk-adapted only), so these rates reflect current real-world management.

Notably, the elevated VTE risk appears to be a feature of the disease biology itself, not mitigated by successive generations of ALK inhibitors.

This raises a focused hypothesis: co-targeting ALK with FAK/PYK2 may modulate upstream drivers of cancer-associated immunothrombosis. PYK2 regulates platelet activation, NETosis, leukocyte–platelet aggregates, and endothelial adhesion.

Given the high inflammatory tone of ALK with tumors, FAK/PYK2 inhibition could plausibly dampen the pro-thrombotic state.

Critically, this is not an alternative to anticoagulation, but a complementary approach. Anticoagulants act downstream on the coagulation cascade, whereas FAK/PYK2 targeting addresses the upstream biology generating thrombotic risk, a layer not currently targeted in standard care.

There is already clinical proof-of-feasibility for this biology. CT-707 (conteltinib), a triple ALK/FAK/PYK2 inhibitor, has shown robust efficacy with manageable safety in early-phase studies, demonstrating that simultaneous ALK with FAK/PYK2 inhibition is deliverable in patients.

In parallel, defactinib (dual FAK/PYK2; FDA-approved in LGSOC) supports pathway tractability and safety, making it a feasible partner to test alongside ALK inhibitors in NSCLC.
BBB penetrant plus

Can ALK inhibition combined with FAK/PYK2 meaningfully modulate the thrombo-inflammatory biology, and thus VTE risk, intrinsic to ALK with NSCLC?

Based on dr. Liu X post.”

Title: Risk Factors for Developing Venous Thromboembolism in Patients with Advanced ALK-Rearranged Non-Small Cell Lung Cancer

Authors: Caroline Kamali, Georgios Tsakonas, Rolf Lewensohn, Lena Kanter, Hanna Vikman, Anders Berglund, Elena Nedbaylo, Per Hydbring, Kristina Viktorsson, Luigi De Petris, Simon Ekman

Oliver Maracic

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ALK Anders Berglund anemia anticoagulants ASCO Blood Caroline Kamali conteltinib Elena Nedbaylo FAK Georgios Tsakonas Hanna Vikman Health Hematology Hemostasis Hemostasis News Hemostasis Today ISTH JTO Clinical and Research Reports Kristina Viktorsson Lena Kanter leukocytosis LGSOC Luigi De Petris Medicine NCCN Netosis NSCLC Oliver Maracic PE Per Hydbring Platelet PYK2 Rolf Lewensohn Simon Ekman TKI VTE
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