A Phase 1/2, Multicenter, Open Label, Dose Escalation and Dose Expansion Study of JK06, a 5T4 Antibody Drug Conjugate, in Patients with Unresectable Locally Advanced or Metastatic Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Salubris Biotherapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

14 Oct 2025 → ongoing

Decision date (initial)

2024-07-18

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Salubris Biotherapeutics, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacokinetic, Therapy, Efficacy, Dose response, Safety

The primary objective of Dose Escalation is to:
• Evaluate the safety, tolerability, MTD/OBD, and/or DLTs of JK06

The primary objectives of Cohort Expansion are to:
• Characterize safety, tolerability and benefit-risk across dose levels to establish a safe and optimized recommended Phase 2 dose (RP2D) of JK06 monotherapy
• Evaluate the preliminary anti-tumor activity of JK06 as measured by ORR in advanced NSCLC and breast cancer patients

Secondary objectives 2

1. The main secondary objectives of Dose Escalation are to: • Characterize the PK of JK06. • Assess the immunogenicity (ADA) of JK06. • Evaluate the preliminary anti-tumor activity of JK06 as measured by ORR according to standard Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Eisenhauer 2009).
2. The main secondary objectives of Cohort Expansion are to: • Further evaluate the efficacy of JK06 by assessing the duration of response (DoR), disease control rate (DCR) and PFS. • Further evaluate the safety of JK06. • Further evaluate the PK of JK06 at specific doses.

Conditions and MedDRA coding

Unresectable, Locally Advanced or Metastatic Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Age ≥ 18 years old.
2. Signed informed consent and willing and able to comply with study procedures and scheduled visits.
3. For Dose Escalation, patients with one of the following histologically diagnosed unresectable, locally advanced, or metastatic tumor types: • Non-small cell lung cancer (NSCLC) • Clear cell or papillary renal cell carcinoma (RCC). • Urothelial bladder cancer (UC). • Head and neck squamous cell cancer (HNSCC). • Breast cancer. • Gastric cancer or gastroesophageal junction adenocarcinoma (GC/GEJ). • Epithelial ovarian cancer. • Cervical cancer. • Endometrial adenocarcinoma. • Prostate cancer. • Soft tissue sarcoma (except any liposarcoma or angiosarcoma). For the escalation cohorts, patients must have experienced progressive disease on or be intolerant to an established standard systemic anti-cancer therapy for a given tumor type or have been intolerant to such therapy, or in the opinion of the Investigator have been considered ineligible for a particular form of standard therapy on medical grounds. Patients must have no available proven curative or life prolonging therapies.
4. For Cohort Expansion, specific cohorts are as follows: a. NSCLC cohort (limited to squamous and non-squamous carcinoma histology only): i. Patients must have received no more than 3 prior lines of therapy in the metastatic setting, including programmed death-1/programmed death-ligand 1 (PD-[L]1) therapy and platinum-based chemotherapy as indicated and locally approved. ii. Patients must have been tested as per standard of care as clinically indicated for relevant tumor mutations, translocation or other genomic aberrations (e.g., epidermal growth factor receptor [EGFR], ROS1, anaplastic lymphoma kinase [ALK] mutations or fusions, etc.) for which an approved targeted therapy is available. – If present, patients must have progressed on or be intolerant to mutation-specific treatment. Note: Targeted therapies for the same actionable mutation count as 1 line of therapy. b. EGFR Mutation Cohort: i. NSCLC patients that have previously had an EGFR mutation detected. ii. Must meet other eligibility criteria outlined in 4a. c. Squamous Carcinoma Cohort: i. NSCLC patients that have squamous cell histology. ii. Must meet other eligibility criteria outlined in 4a. d. Breast cancer cohort: histologically confirmed diagnosis of advanced and/or metastatic breast adenocarcinoma. Patients must have had recurrence, progression or intolerance to standard therapy as noted here: i. HER2-negative/hormone receptor-positive breast cancer: consisting of at least 2 prior standard regimens for metastatic disease but no more than 4 regimens. Hormonal, including therapies for ESR1 mutant breast cancer, and targeted regimens without concomitant chemotherapy will not be counted as lines of therapy, including but not limited to CDK, PI3K, and AKT-targeted therapies. ii. HER2-positive breast cancer: consisting of at least 3 prior standard anti-HER2 targeted treatments in the metastatic setting. iii. Triple-negative breast cancer: consisting of at least 2 prior standard regimens for metastatic disease but no more than 4 regimens. NOTE: Patients who are inappropriate candidates for or have refused treatment with these regimens are also eligible e. Basket cohort: patients with histologically diagnosed unresectable, locally advanced or metastatic tumor types listed here and have experienced progressive disease on an established standard systemic anti-cancer therapy for a given tumor type or have been intolerant or is ineligible to such therapy per investigator’s assessment (specific restrictions by tumor type are noted): i. Prostate cancer: adenocarcinoma without the presence of dominant histopathological features representative of sarcomatoid, spindle cell, or neuroendocrine small cell components, has been treated with ≥ 1 prior taxane regimen (e.g., docetaxel, cabazitaxel), and has documented progressive metastatic castration-resistant prostate cancer (mCRPC) disease according to the following (at least 2 of 3): – Serum prostate-specific antigen (PSA) progression defined as 2 consecutive increases in PSA over a previous reference value with minimal value ≥ 2 ng/mL – Soft tissue progression as defined by RECIST 1.1 – Progression of bone disease as defined by PCWG3 criteria ii. Endometrial cancer: restricted to clear cell or papillary adenocarcinoma iii. Esophageal cancer: restricted to squamous cell carcinoma iv. Cervical cancer
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
6. Life expectancy ≥ 12 weeks.
7. Measurable disease as per RECIST 1.1 criteria and documented by computed tomography (CT) and/or magnetic resonance imaging (MRI); for prostate cancer cohort, measurable disease or bone lesions that are evaluable according to PCWG3 criteria. Note: Target lesions treated previously with radiation must demonstrate clear evidence of radiographic progression since the completion of prior radiotherapy and prior to study enrollment.
8. Acceptable laboratory parameters: • Albumin ≥ 2.8 g/dL. • Platelet count ≥ 100, 000. • Hemoglobin ≥ 9.0 g/dL. • Absolute neutrophil count ≥ 1,500/μL. • ALT/AST ≤ 3.0 times ULN. − ALT/AST ≤ 5 × ULN for patients with liver metastases. Total bilirubin ≤ 1.5 ULN or ≤ 3 x ULN for patients with Gilbert’s disease. • Direct bilirubin ≤ 1.5 ULN for patients with total bilirubin > 1.5 ULN. • Creatinine ≤ 1.8 mg/dL. − Or calculated/measured creatinine clearance > 30 mL/minute.
9. Identification of an archival tumor sample (i.e., tissue block (formalin-fixed paraffin-embedded [FFPE]) or a series of approximately 10-15 slides).
10. Consent to pre-treatment fresh tumor biopsy for patients enrolled in the backfill part of Dose Escalation and all eligible patients enrolled in Cohort Expansion. Those patients for whom only bone biopsies are available or feasible will be exempted from this requirement.
11. Women of childbearing potential (WOCBP) not surgically sterilized and between menarche and 1 year post menopause must: • Have a negative serum or urine pregnancy test performed within 72 hours prior to the initiation of study drug administration. • Be willing to use 2 forms of effective contraception throughout the study, starting with the screening and through 217 days after the last dose of JK06. − A comprehensive list of all highly effective birth control methods is included in Appendix 2. • Abstinence is considered a highly effective method if this is the established and preferred contraception method for the patient and is defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods], withdrawal, spermicides only, and lactational amenorrhea method are not acceptable methods of contraception. Female and male condoms should not be used together
12. Male patients with partners of childbearing potential, even if surgically sterilized (i.e., status post-vasectomy) must agree to: • Use effective barrier contraception from the time of consent through 217 days after discontinuation; or • Agree to practice true abstinence, if this is the established and preferred contraception method by the patient and is defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. Periodic abstinence [e.g., calendar, symptothermal, post-ovulation methods], withdrawal, spermicides only, and lactational amenorrhea method are not acceptable methods of contraception. Female and male condoms should not be used together. • In addition, male patients should also have their partners use contraception (as documented for female patients in Appendix 2) for the same period.
13. Central nervous system (CNS) metastases must have been treated, be asymptomatic for ≥ 14 days, and meet the following at the time of enrollment: • No concurrent treatment for CNS disease (e.g., surgery, radiation, corticosteroids ≥ 10 mg prednisone/day or equivalent). • No concurrent or history of leptomeningeal disease or cord compression.
14. Must be willing and able to comply with clinic visits and procedures outlined in the study protocol.
15. Concurrent use of hormones for breast cancer or for non-cancer related conditions (e.g., insulin for diabetes, hormone replacement therapy) is acceptable. Bisphosphonates or RANK-L inhibitors or analogues are permitted for supportive care of patients with bone metastases.

Exclusion criteria 16

1. Patients with symptomatic or unstable CNS primary tumor or metastases and/or carcinomatous meningitis. Patients with documented treated CNS metastases stable for at least 4 weeks may be enrolled at the discretion of the investigator.
2. Any serious underlying medical or psychiatric condition that would preclude understanding and rendering of informed consent or impair the ability of the patient to receive or tolerate the planned treatment.
3. Recent or ongoing serious infection including the following: • Any uncontrolled Grade ≥3 (per CTCAE v5.0) viral, bacterial, or fungal infection within 2 weeks prior to the first dose of JK06. Routine antimicrobial prophylaxis is allowed. • Uncontrolled infection with human immunodeficiency virus (HIV). Patients on stable highly active antiretroviral therapy (HAART) with undetectable viral load and normal CD4 counts for at least 6 months prior to study entry are eligible. Serological testing for HIV at screening is not required. • Known to be positive for hepatitis B (HBV) surface antigen, or any other positive test for hepatitis B indicating acute or chronic infection. Patients who are or have received anti-HBV therapy and have undetectable HBV DNA for at least 6 months prior to study entry are eligible. Serological testing for HBV at screening is not required. • Known active hepatitis C (HCV) as determined by positive serology and confirmed by polymerase chain reaction (PCR). Patients on or having received antiviral therapy are eligible provided they are virus-free by PCR for at least 6 months prior to study entry. Serological testing for HCV at screening is not required. • Known active or latent tuberculosis (testing at screening not required).
4. Prior systemic anti-cancer treatment: • For cytotoxic chemotherapy, small molecule inhibitors, radiation, or similar investigational treatments, ≤ 2 weeks or 5 half-lives, whichever is shorter. • For monoclonal antibodies or similar experimental therapies: ≤ 3 weeks or 5 half-lives, whichever is shorter. • Antibody drug conjugates and radioimmunoconjugates or other similar experimental therapies ≤ 6 weeks or 5 half-lives, whichever is shorter. •Any prior treatment targeting 5T4.
5. Ascites or pleural effusions requiring large volume para- or pleurocentesis within 4 weeks of treatment initiation.
6. Pregnant or nursing.
7. Therapeutic anticoagulation for a thromboembolic event that occurred within 3 months of dosing; prophylactic anticoagulation is permitted.
8. Major surgery within 6 weeks from treatment initiation.
9. Clinically significant cardiovascular/vascular disease ≤ 6 months before first dose: • Myocardial infarction or unstable angina. • Clinically significant cardiac arrhythmias. • Uncontrolled hypertension: systolic blood pressure (SBP) > 180 mmHg, diastolic blood pressure (DBP) > 100 mmHg. Pulmonary embolism, symptomatic cerebrovascular events or any other serious cardiac condition (e.g., pericardial effusion or restrictive cardiomyopathy). • QTcF prolongation > 480 msec. • Congestive heart failure (New York Heart Association class III-IV). • Myocarditis/clinically significant pericarditis.
10. Clinically significant gastrointestinal disorders including: • Gastrointestinal perforation or unhealed ulcerations < 6 months prior to study drug administration. Patients must have documented evidence (e.g., upper endoscopy, colonoscopy) of completely healed area of prior perforation. • Clinically significant gastrointestinal bleeding < 3 months prior to study drug administration. • Pancreatitis < 6 months prior to study drug administration. • History of Crohn’s disease or ulcerative colitis.
11. Clinically significant pulmonary compromise requiring supplemental oxygen use.
12. Grade ≥2 peripheral neuropathy at time of study entry.
13. Vaccination with any live virus vaccine within 4 weeks prior to the initiation of study drug administration. Inactivated annual influenza vaccination is allowed.
14. Known hypersensitivity to JK06 or any excipient.
15. Second primary invasive malignancy not in remission for ≥ 1 year. Exceptions include non-melanoma skin cancer, cervical carcinoma in situ, resected melanoma in situ, or any malignancy considered to be indolent and never required therapy.
16. Active pneumonitis/interstitial lung disease (ILD) or history of drug-induced or radiation-induced pneumonitis/ILD that requires ongoing systemic corticosteroid treatment or has not fully resolved at study entry. Note: Asymptomatic, radiographic findings consistent with chronic fibrotic change (e.g., post-treatment scarring) without clinical evidence of active pneumonitis do not constitute exclusion.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. For Dose Escalation : MTD/OBD and/or DLT during the DLT evaluation period and all serious adverse events, adverse events tabulated/reported by type, grade, and frequency for the entire study duration.
2. For Cohort Expansion: • RP2D based on the totality of the data and primarily based on the ORR and AE & SAE. • ORR according to RECIST 1.1 (Eisenhauser 2009) or PCWG3 criteria (Scher 2016).

Secondary endpoints 2

1. For dose Escalation : •PK (analysis of Cmax, AUC, Tmax, and t½ following treatment completion). • ADA status. • ORR according to standard RECIST 1.1 criteria (Eisenhauer 2009).
2. For Cohort Expansion: •Evaluate DoR, DCR, and PFS according to RECIST 1.1 (Eisenhauer 2009) or PCWG3 criteria (Scher 2016). • Evaluate AEs/SAEs tabulated by tumor type. • PK (analysis of maximum observed drug concentration [Cmax], AUC, time to maximum observed drug concentration (Tmax), and terminal elimination half-life (t½) following treatment completion) evaluation by dose and tumor type.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Salubris Biotherapeutics Inc.

Sponsor organisation

Salubris Biotherapeutics Inc.

Address

45 West Watkins Mill Road Suite E

City

Gaithersburg

Postcode

20878-4026

Country

United States

Scientific contact point

Organisation

Salubris Biotherapeutics Inc.

Contact name

Naimish Pandya

Public contact point

Organisation

Salubris Biotherapeutics Inc.

Contact name

Naimish Pandya

Third parties 3

Locations

2 EU/EEA countries · 14 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 4 · Art. 38 CTR

Urgent safety measures 1 · Art. 54 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 35 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications