A Phase 2, Open-Label Study to Evaluate the Safety and Effects of HLX-1502 in Patients With Neurofibromatosis Type 1

Inclusion Criteria:

1. All participants must have a diagnosis of NF1 based on the 2021 revised consensuscriteria.

2. Participants must have PN(s) that are progressive OR are causing significantmorbidity, such as (but not limited to) head and neck lesions that are compromisingthe airway or great vessels, brachial or lumbar plexus lesions that are causingnerve compression and loss of function, lesions causing significant disfigurement (e.g., orbital lesions), lesions of the extremity that cause limb hypertrophy orloss of function, and painful lesions. Participants with paraspinal PN will beeligible for this trial. Histologic confirmation of tumor is not necessary butshould be considered if there are clinical or radiographic findings concerning formalignant transformation of a PN.

3. Measurable Disease: Participants must have measurable PN(s) amenable to volumetricMRI analysis. For the purpose of this study, the target lesion must be seen on atleast 3 consecutive MRI slices and the field of view must contain the entire tumorof interest. Tumors must be at least 3 mL in volume (most PN 3 cm in longestdiameter will meet this criteria). If the tumor is < 3 cm in longest diameter, theparticipant may still be eligible. Central review of the MRI of the target PN isrequired prior to enrollment to ensure that the tumor is measurable and amenable tovolumetric analysis.

4. Age: Participants must be ≥ 12 years of age at the time of study entry. Note:Although prior MEKi therapy is not a requirement, patients should be counseled onthe availability of FDA-approved MEKi therapies prior to enrollment.

5. Weight ≥ 42 kg.

6. Performance Level: Participants must have a Lansky (12-15 years of age) or Karnofsky (16+ years of age) score ≥ 50%.

7. Organ Function Requirements: Adequate Bone Marrow Function, Adequate Renal Function,Adequate Liver Function, Normal pancreatic function: amylase and lipase levels ≤ 1.5x ULN. Blood pressure within upper limit of normal as defined below based on theaverage of the 2nd and 3rd of a total of 3 consecutive measurements, 5 minutesapart. Antihypertensives are permissible to achieve blood pressure within ULN,however must be on stable antihypertensive regimen with no adjustments within 14days of enrollment.

8. Sexually active women of childbearing potential and fertile male participants andtheir partners must agree to use effective methods of contraception e.g., hormonaloral contraception, injectables, intrauterine device, surgical sterilizationincluding vasectomy, or hormonal implant with barrier methods (male condom, femalecondom, or diaphragm with spermicidal gel) during the course of the study and for 4months after the last dose of study treatment. Barrier methods alone areinsufficient. True sexual abstinence or evidence of surgical sterility (e.g.vasectomized partner, post-hysterectomy, menopause with last menstrual period >=12months prior to screening visit) are acceptable method of birth control. Persons ofchildbearing potential will be given a pregnancy test within 14 days prior to firstdose of study treatment and must have a negative urine or serum pregnancy test.

9. The participant is not planning to undergo surgery or other interventions/treatments for the target lesion, except protocol specified therapy, for theduration of the study.

10. The participant or the participant's legal authorized representative is able tounderstand the informed consent form describing the risks of the study andvoluntarily signs the informed consent document.

11. In the opinion of the investigator, the participant is willing and able to attendstudy visits, comply with the study procedures as specified in the protocol, andcomply with the administration of the study drug.

Exclusion Criteria:

1. Prior treatment with HLX-1502 for a PN.

2. The participant has used any of the following systemic medications/ therapies withinthe specified period prior to enrollment: MEK-inhibitors, other drugs in the TKIclass, HLX-1502, Participants may have received treatment for a PN or othertumor/malignancy but must have fully recovered to baseline or CTCAE ≤ Grade 1 fromacute toxicities from prior therapies except alopecia, Myelosuppressivechemotherapy, Hematopoietic growth factors, Biologic (anti-neoplastic agent),Investigational Drugs, Any other systemically administered anti-neoplastic agent andRadiation therapy.

3. Evidence of an NF1-related tumor such as optic pathway or other low-grade glioma,high-grade glioma, malignant peripheral nerve sheath tumor, or other cancer/tumorrequiring treatment with chemotherapy, biologic therapy, surgery or radiationtherapy.

4. Participants with high-grade glioma, malignant peripheral nerve sheath tumor, orother malignancy who received treatment in the last 12 months. Exceptions includebasal cell carcinoma of the skin and squamous cell carcinoma of the skin that haveundergone potentially curative therapy. If the investigator has any clinicalconcerns for ANNUBP/Atypical Neurofibroma or MPNST, a biopsy sample must be takenprior to study confirming eligibility.

5. Dental braces or prosthesis that interfere with volumetric analysis of theneurofibroma(s).

6. Surgery: Any major surgery within 12 weeks before starting the Treatment Period orforeseen during participation in the trial, any minor surgeries within 1 monthbefore first dose of study treatment and Participants must have complete woundhealing from major surgery or minor surgery before the first dose of studytreatment. Participants with clinically relevant ongoing complications from priorsurgery are not eligible.

7. Cataracts noted on ophthalmologic exam.

8. Cardiovascular disorders.

9. Other clinically significant disorders that would preclude safe study participation,including active infection, a known history of HIV seropositivity or knownimmunodeficiency or Known history of Hepatitis B or Hepatitis C.

10. Participants who require treatment with a drug that is a substrate of CYP1A2,CYP2C8, UGT1A1, UGT1A3 with a narrow therapeutic index during protocol therapy.

11. Known severe sensitivity to HLX-1502 or any excipient of HLX-1502 or history ofallergic reactions attributed to compounds of similar chemical or biologiccomposition to HLX-1502.

12. Known severe sensitivity to FD&C Yellow No. 5.

13. Participants receiving therapeutic anticoagulation with vitamin K antagonist.

14. Participants presently with iron deficiency and/or actively receiving ironreplacement or requiring treatment with copper or zinc for any indication at studybaseline.

15. Pregnant or breast-feeding women.

16. Unable or unwilling to swallow tablets.

17. Impairment of gastrointestinal function or gastrointestinal disease that maysignificantly alter ingestion and/or the absorption of HLX-1502.

18. Participants who have other medical, social or concurrent challenges that are likelyto negatively impact their ability to meet all of the trial obligations andtherefore may increase the risk of safe participation in the study.