Salubris Biotherapeutics announced encouraging Phase 1 dose escalation results for JK06, a novel 5T4-targeted antibody drug conjugate (ADC), at the European Society for Medical Oncology (ESMO) Congress. The first-in-class quadrivalent, biparatopic ADC demonstrated notable antitumor activity in heavily pretreated patients with advanced solid tumors, particularly showing promise in non-small cell lung cancer (NSCLC) and breast cancer.
Clinical Trial Design and Patient Population
The Phase 1/2 open-label, dose-escalation study (NCT06667960) enrolled 34 patients in Europe with advanced relapsed/refractory solid tumors. Patients received JK06 once every three weeks across five dose levels ranging from 1.5 to 8.0 mg/kg. Among the enrolled patients, 29 were response-evaluable, all having failed standard of care therapy. The patient population was heavily pretreated, with 83% having received three or more prior lines of treatment and 59% having received four or more prior lines of therapy at enrollment.
Efficacy Results Show Promise in NSCLC
Among the 29 response-evaluable patients, six achieved confirmed partial responses (PRs), representing an overall response rate of 21%. The most striking results were observed in NSCLC patients, where five of 13 evaluable patients attained confirmed PRs, yielding an objective response rate of 38%. The longest duration of response in NSCLC patients lasted 30 weeks.
In breast cancer patients, one of seven response-evaluable patients achieved a confirmed PR with a duration of response lasting 18 weeks. Partial responses were observed across multiple dose levels: 3.0 mg/kg (1 NSCLC), 4.5 mg/kg (3 NSCLC and 1 breast cancer), and 6.0 mg/kg (1 NSCLC).
Safety Profile Supports Continued Development
JK06 demonstrated a generally well-tolerated safety profile with predominantly low-grade (Grades 1 and 2) manageable toxicities. Common adverse events included fatigue, alopecia, decreased appetite, dry eye, and diarrhea. Among treatment-related adverse events occurring in at least 5% of patients, only limited Grade 3 or higher events were observed.
At lower dose levels (1.5-3.0 mg/kg) in 12 patients, one patient experienced Grade 3 peripheral neuropathy. At the 4.5 mg/kg dose level in 15 patients, one patient developed Grade 3 keratitis. At higher dose levels (6.0-8.0 mg/kg) in seven patients, adverse events included one patient each with Grade 3 fatigue, Grade 3 ALT increase, and one Grade 5 pneumonitis event.
Pharmacokinetic analysis revealed favorable free monomethyl auristatin E (MMAE) levels at dose levels up to 4.5 mg/kg, supporting the therapeutic window for JK06.
Novel Mechanism and Target Profile
JK06 represents a first-in-class quadrivalent, biparatopic ADC that selectively targets 5T4 with an MMAE payload. The 5T4 target is an oncofetal protein overexpressed in a wide range of solid tumors, including NSCLC, breast, renal, and genitourinary cancers. This overexpression is associated with more aggressive tumor progression and reduced survival outcomes.
The biparatopic design of JK06 enables picomolar affinity for 5T4 and rapid internalization. Combined with stable, site-specific payload conjugation, JK06 demonstrated robust efficacy and a clean safety profile in non-clinical studies.
Next Steps and Future Development
"We are encouraged by the promising preliminary data demonstrating the combination of safety and efficacy of JK06 among heavily pre-treated metastatic solid tumors, including in NSCLC and breast cancer, supporting our belief that JK06 has the potential to be a first-in-class, differentiated therapy for patients with 5T4-expressing cancers," said Sam Murphy, Chief Executive Officer of Salubris Biotherapeutics.
The company is advancing the study into dose expansion with tumor-specific cohorts for NSCLC and breast cancer. The ongoing cohort expansion phase, which is currently enrolling, will determine the recommended Phase 2 dose for further development. Salubris also plans to continue exploring activity in other solid tumors known to overexpress 5T4.
