Testing a new drug for advanced solid tumors that express c-Kit

A Phase 1 Dose Escalation and Expansion Study of the c-Kit Specific Antibody-Drug Conjugate NN3201 in Subjects With Advanced and/or Metastatic Solid Tumors Known to Express c-Kit

This study is testing a new drug for people with advanced solid tumors that have a specific marker called c-Kit to see if it is safe and how well it works.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 67 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Novelty Nobility, Inc. (industry)
• Drugs / interventions: imatinib, chemotherapy, immunotherapy, radiation, prednisone
• Locations: 5 sites (Ann Arbor, Michigan and 4 other locations)
• Trial ID: NCT06805825 on ClinicalTrials.gov

What this trial studies

This open-label clinical trial evaluates the safety and tolerability of NN3201, a c-Kit targeting antibody-drug conjugate, in patients with advanced and/or metastatic solid tumors known to express c-Kit. The study consists of two parts: a dose escalation phase to determine the maximum tolerated dose and an expansion phase to further assess safety at the recommended dose. Eligible patients include those with gastrointestinal stromal tumors, small-cell lung cancer, adenoid cystic carcinoma, uveal melanoma, neuroendocrine tumors, and certain renal cell carcinomas who have previously received treatment or are ineligible for standard therapies.

Who should consider this trial

Good fit: Ideal candidates are patients with advanced or metastatic solid tumors that express c-Kit and have either received prior treatment or are intolerant to standard therapies.

Not a fit: Patients with early-stage tumors or those who do not express c-Kit may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat solid tumors expressing c-Kit.

How similar studies have performed: Other studies targeting c-Kit have shown promise, suggesting potential for success with this approach.

Eligibility criteria

Key Inclusion Criteria:

Subjects must meet the following criteria to be eligible for enrollment into the study:

1. Histologically or cytologically confirmed locally advanced, metastatic, and/or unresectable GIST, SCLC, ACC, uveal melanoma, NET ChRCC or ccRCC.
2. Subjects must have received the following treatment:

   Part A (Dose Escalation):

   i. Treatment with imatinib for GIST (at least one line of therapy with imatinib)

   or

   ii. Progressive/refractory, ineligible, or intolerant to available standard therapy (or subject declines standard therapy) for c-Kit-associated solid tumors (ACC, uveal melanoma, NET ChRCC or ccRCC)

   Part B (Dose Expansion):

   i. Treatment with imatinib for GIST (at least one line of therapy with imatinib) or

   ii. Progressive/refractory, ineligible, or intolerant to available standard therapy (or subject declines standard therapy) for Extensive stage SCLC or

   iii. Progressive/refractory, ineligible, or intolerant to available standard therapy (or subject declines standard therapy) for c-Kit-associated solid tumors (ACC, uveal melanoma, NET or ChRCC or ccRCC).
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4. Life expectancy ≥ 3 months before starting NN3201 in the opinion of the Investigator.
5. Age ≥ 18 years.
6. Laboratory values demonstrating adequately functioning kidney, liver and bone marrow (hematology).
7. Adequate heart function as measured by ECHO/MUGA scan.
8. Time between prior anticancer therapy including investigational agents and first dose of NN3201 as below:

   1. Cytotoxic chemotherapy - At least 21 days
   2. Non-cytotoxic chemotherapy (e.g., small molecule inhibitor) - At least 14 days
   3. Nitrosoureas - At least 6 weeks
   4. Monoclonal antibody(ies) - At least 28 days
   5. Radiotherapy - At least 14 days from local site radiation therapy
9. Negative Serum/urine pregnancy test (for subjects of childbearing potential)
10. All subjects of childbearing potential must agree to use contraception throughout the study and for additional 120 days after the last dose of assigned treatment. Subjects must refrain from donating sperm during the same period or Subjects who do not have childbearing potential are confirmed post-menopausal or sterile.
11. Voluntary agreement to provide written informed consent and have willingness and ability to comply with all aspects of the protocol.

Key Exclusion Criteria:

1. Has received prior therapy with a c-Kit agent (except GIST subjects).
2. Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms.
3. A condition requiring systemic treatment with corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to administration of study drugs (inhaled corticosteroids are allowed).
4. Any prior treatment-related (i.e., chemotherapy, immunotherapy, radiotherapy) clinically significant toxicities that have not resolved to Grade ≤ 1 or prior treatment-related toxicities that are clinically unstable and clinically significant at Study Entry, Day -2 to Cycle 1 Day 1.
5. Major surgery within 30 days before the first dose of study drug treatment in Cycle 1 on Day 1 (port placement for venous access is not considered major surgery).
6. Significant cardiovascular impairment.
7. Significant screening electrocardiogram (ECG) abnormalities.
8. Known active and clinically significant bacterial, fungal, or viral infection.
9. Uncontrolled hypertension defined as systolic blood pressure ≥ 160mmHg and/or diastolic blood pressure ≥ 100mmHg, despite optimal medical management.
10. Venous thrombosis or pulmonary embolism within the last 3 months prior to the screening.
11. Ongoing or active infection requiring intravenous treatment with anti-infective therapy or systemic therapy and/or any identified active COVID-19 infection.
12. Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the subject's participation in this study.
13. People who are pregnant or breastfeeding.

Other inclusion and exclusion criteria must also be met to be eligible to participate in this study.

Where this trial is running

Ann Arbor, Michigan and 4 other locations

• University of Michigan Hospitals — Ann Arbor, Michigan, United States (RECRUITING)
• Case Comprehensive Cancer Center — Cleveland, Ohio, United States (RECRUITING)
• Oregon Health & Science University — Portland, Oregon, United States (RECRUITING)
• The University of Texas MD Anderson Cancer Center — Houston, Texas, United States (RECRUITING)
• NEXT Virginia — Fairfax, Virginia, United States (ACTIVE_NOT_RECRUITING)

Study contacts

• Principal investigator: Sunil Sharma, MD — Novelty Nobility
• Study coordinator: Clinical Trial Lead

Conditions: Gastrointestinal Stromal Tumors, Small-cell Lung Cancer, Adenoid Cystic Carcinoma, Uveal Melanoma, Neuroendocrine Tumors, Chromophobe Renal Cell Carcinoma, Clear Cell Renal Cell Carcinoma, GIST