Study of JANX008 in Subjects With Advanced or Metastatic Solid Tumor Malignancies

Study Overview
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Brief Summary
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This study is a first-in-human (FIH), Phase 1/1b, open-label, multicenter dose escalation and dose expansion study to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary anti-tumor activity of JANX008 in adult subjects with advanced or metastatic carcinoma expressing EGFR.

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

Conditions
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Non-Small Cell Lung Cancer, Renal Cell Carcinoma, Squamous Cell Carcinoma of the Head and Neck, Colorectal Carcinoma

Intervention / Treatment
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* Drug: JANX008


Participation Criteria
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Eligibility Criteria
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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, or RCC 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation<br>Subjects will be dosed weekly during each 21-day cycle. Dosage per cohort will increase to determine the maximum tolerable dose. | Drug: JANX008<br>* JANX008 is dosed via IV weekly in a 21-day cycle<br>|
| Experimental: Backfill Expansion<br>Subjects will be dosed weekly during each 21-day cycle. Subjects will be dosed at levels previously declared tolerable. | Drug: JANX008<br>* JANX008 is dosed via IV weekly in a 21-day cycle<br>|
| Experimental: Expansion<br>Subjects will be dosed weekly during each 21-day cycle. Subjects will be dosed at the preliminary recommended Phase 2 dose (RP2D). | Drug: JANX008<br>* JANX008 is dosed via IV weekly in a 21-day cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Dose Limiting Toxicities (DLT) |  | 21 days | 
| Incidence of Adverse Events (AE) and Serious Adverse Events (SAE) |  | Up to 4 years | 
| Incidence of Clinically Significant Laboratory Abnormalities |  | Up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration time curve from time 0 to last timepoint prior to next dose JANX008 (AUC last) |  | Pre-dose and at multiple timepoints post-dose on Days 1, 2, 4, 8, 9, 15, 16, 18 up to end of treatment (Up to 4 years) | 
| Maximum observed concentration of JANX008 (Cmax) |  | Pre-dose and at multiple timepoints post-dose on Days 1, 2, 4, 8, 9, 15, 16, 18 up to end of treatment (Up to 4 years) | 
| Number of participants who develop anti-drug antibodies against JANX008 |  | Up to 4 years | 
| Overall Response Rate | Proportion of participants who achieve a complete response or partial response per RECIST v1.1 | Up to 4 years | 
| Duration of Response | Time from documentation of CR or PR to disease progression per RECIST v1.1 | Up to 4 years | 
| Progression Free Survival | Time from treatment initiation to disease progression per RECIST v1.1 | Up to 4 years | 
| Correlation of EGFR expression level with anti-tumor activity and safety |  | Up to 4 years |