An Open-Label, Multicenter, Phase 1/1b Study of JANX008 in Subjects with Advanced or Metastatic Solid Tumor Malignancies

Overview

JANX008 (EGFR-TRACTr; EGFRxCD3-TRACTr) is a tumor-activated, bispecific T‑cell engager targeting EGFR and CD3 that is being evaluated in an open‑label, first‑in‑human Phase 1/1b trial for adults with advanced/metastatic EGFR‑expressing solid tumors (including NSCLC, RCC, CRC, SCCHN, SCLC, PDAC, and TNBC). The trial (NCT05783622) began in April 2023 and remains recruiting as of updates posted July–August 2025. (clinicaltrials.ucsd.edu)

Mechanism of action

JANX008 is a tri‑specific protein engineered with: - EGFR‑binding and CD3‑binding domains to redirect T cells to EGFR‑expressing tumor cells. - An albumin‑binding domain to extend half‑life. - Two peptide “masks” linked by tumor‑protease–cleavable sequences that suppress binding to EGFR and CD3 in circulation; proteolysis in the tumor microenvironment unmasks activity, aiming to reduce cytokine release syndrome (CRS) and on‑target, off‑tumor EGFR toxicities. Preclinical studies demonstrated cleavage‑dependent T‑cell killing and favorable tolerability in non‑human primates. (aacrjournals.org)

Clinical development

• Study design: Phase 1/1b, dose‑escalation with backfill and expansion cohorts; weekly IV dosing on 21‑day cycles; primary endpoints include DLTs and safety; secondary endpoints include ORR (RECIST v1.1), DoR, PFS, PK/PD, and immunogenicity. (clinicaltrials.ucsd.edu)
• Status/timelines: Recruiting across multiple U.S. centers; estimated primary completion January 2026 and study completion October 2027 (as listed on registry aggregators). Company reports ongoing enrollment and that additional program updates are planned in the second half of 2025. (cdek.pharmacy.purdue.edu)

Efficacy

Human efficacy data are preliminary. In a company‑reported interim update with data cut February 12, 2024 (n=11 across tumor types; dose levels up to 1.25 mg weekly), one patient with NSCLC treated at 0.15 mg weekly had a confirmed partial response by RECIST, including 100% reduction of the target lung lesion and elimination of liver metastasis; this response was maintained through week‑18 at the time of the report. A patient with RCC had a 12% tumor reduction with clinical benefit. No response rates by cohort or tumor‑specific ORR were reported. (businesswire.com)

Safety

In the same interim dataset (as of February 12, 2024; 11 heavily pretreated subjects): - CRS: Grade 1 CRS in 2/11 patients; no Grade ≥2 CRS observed. - Other AEs: Most treatment‑related AEs were Grade 1–2, mainly in cycle 1. - No treatment‑related serious AEs or dose‑limiting toxicities were observed at doses up to 1.25 mg weekly (noted as above the projected MTD of the parental, unmasked TCE). (investors.januxrx.com)

Notes and context

• As of October 2025, there are no peer‑reviewed clinical efficacy/safety publications for JANX008; available human data are from company press releases and website disclosures. Preclinical mechanistic details are described in an AACR‑published abstract. (aacrjournals.org)

Further reading

• Trial registry and key details: NCT05783622 (institutional mirror page with study synopsis, eligibility, and sites). (clinicaltrials.ucsd.edu)
• Company interim clinical update for JANX008 (February 26, 2024). (businesswire.com)
• Company investor page summarizing early JANX008 safety observations. (investors.januxrx.com)
• Preclinical abstract: “Preclinical activity and safety profile of JANX008, a novel EGFR‑targeting tumor‑activated T‑cell engager” (AACR/Cancer Immunology Research, abstract B04). (aacrjournals.org)
• Company clinical‑trials overview for JANX008 (links through to NCT05783622). (januxrx.com)

Disclaimer: Investigational agent; safety and efficacy have not been established. All clinical findings above reflect early, small‑sample, company‑reported data and may evolve with ongoing dose‑escalation and planned expansions. (investors.januxrx.com)

Last updated: Oct 2025

Inclusion Criteria:

* Subjects ≥18 years of age at the time of signing informed consent

* Histologically or cytologically documented locally advanced or metastatic NSCLC, SCCHN, CRC, RCC, SCLC, PDAC, TNBC

* Progressed or was intolerant to all available therapies known to confer clinical benefit appropriate for the tumor type

* Adequate organ function

* At least 1 measurable lesion per RECIST 1.1

Exclusion Criteria:

* Treatment with anti-cancer therapy within 28 days or ≤5 elimination half-lives, whichever is earlier, before enrollment

* Prior treatment with EGFR-targeted bispecific T cell engager or CAR-T cell therapy

* Prior treatment with CD3 engaging bispecific antibodies

* Clinically significant cardiovascular diseases

* Active clinically significant infection (bacterial, viral, fungal, mycobacteria, or other)

* On supplemental oxygen

* Any medical condition or clinical laboratory abnormality likely to interfere with assessment of safety or efficacy of study treatment