A Phase Ib Study of Subcutaneous FL115 Monotherapy in Participants With Advanced Solid Tumors

An Open-label, Multicenter, Dose-escalation Phase Ib Clinical Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics and Pharmacodynamics of FL115 Injection Administered Subcutaneously as Monotherapy in Participants With Advanced Solid Tumours

This is an open-label, multicenter, dose-escalation Phase Ib clinical study to evaluate the safety, tolerability, efficacy, PK, and PD of FL115 injection administered subcutaneously as monotherapy in participants with advanced solid tumours. All enrolled participants will receive FL115 by subcutaneous injection. Each treatment cycle comprises 21 days, with administration once every 3 weeks (Q3W). Treatment will continue until initiation of new anti-tumour therapy, progressive disease (PD), unacceptable toxicity, death, withdrawal of informed consent, loss to follow-up, or study termination by the Sponsor, whichever occurs first.

Inclusion Criteria:

1. Male or female participants aged ≥18 and ≤80 years.
2. Able to understand and willing to sign the Participant Information and Consent Form (PICF).
3. Participants with histologically or cytologically confirmed locally advanced unresectable and/or metastatic solid tumours who have disease progression after standard therapy, are intolerant to standard therapy, or for whom no standard therapy is available.
4. The participant must have received and progressed on checkpoint inhibitors (CPIs).
5. At least 4 weeks since prior major surgery and recovered from its effects (per investigator judgment).
6. With at least one measurable lesion (according to RECIST v1.1).
7. ECOG score: 0 - 1.
8. Life expectancy ≥12 weeks (as judged by the investigator).
9. Adequate organ function.
10. Fertile subjects (male and female) and their partners agree to use acceptable, investigator-approved contraception during the study-required period.

Exclusion Criteria:

1. Prior Anti-tumour Therapy:

   1. Prior treatment with IL-2/IL-15 agonists;
   2. Prior anti-tumour therapy without completion of the required washout period before first dose;
   3. Participants who have previously received extensive radiotherapy;
   4. Prior treatment with 3 or more lines of checkpoint inhibitors (CPIs).

2. Other Prior Therapies and Recovery from Toxicities:

   1. Known or suspected allergy to FL115 or its excipients;
   2. Systemic immunomodulatory therapy within 4 weeks before first dose, except: hormone doses of ≤10 mg/day prednisone equivalent; topical, inhaled, or intranasal corticosteroids; prophylactic single use of corticosteroids before contrast-enhanced imaging for participants with contrast media allergy;
   3. History of allogeneic organ transplant or allogeneic peripheral blood stem cell (PBSC)/bone marrow transplant;
   4. Receipt of a live virus vaccine within 4 weeks prior to the first dose of the investigational product;
   5. Prior Grade ≥3 irAEs or irAEs leading to discontinuation of immunotherapy;
   6. AEs from prior anti-tumour therapy not recovered to baseline or Grade ≤1 (NCI-CTCAE v5.0) before first dose. Exceptions: alopecia (any grade), peripheral sensory neuropathy (≤Grade 2), hypothyroidism controlled with HRT, or other conditions specified as permissible in the inclusion/exclusion criteria may be enrolled; other AEs (≤Grade 2) approved by the investigator and Sponsor medical monitor.

3. Prior Medical and Surgical History:

   1. Participants with metastases to meninges, or symptomatic brain metastasis, or brain metastasis that has been stable for less than 4 weeks after treatment prior to the first dose , or with spinal cord compression or carcinomatous meningitis;

   2. Participants with other malignant diseases within 2 years prior to screening tests, other than the disease under study. Participants with curable local tumours (e.g., basal or squamous cell skin cancer, cervical or breast cancer in situ) may be enrolled after definitive cure;

   3. Active autoimmune disease or a known history of autoimmune disease requiring systemic hormones or immunosuppressants;

   4. Participants with a history of any of the following pulmonary toxicities:

      1. Clinically significant severe lung-specific diseases;
      2. Active interstitial lung disease (ILD) or interstitial pneumonitis; history of ILD or (non-infectious) pneumonitis requiring treatment with corticosteroids or other immunosuppressants;
      3. Active pulmonary tuberculosis infection within 1 year prior to enrolment, or a history of active pulmonary tuberculosis infection more than 1 year ago without standard treatment, as identified by medical history.

   5. Uncontrolled pleural effusion, pericardial effusion, or ascites as judged by the investigator ;

   6. History of clinically significant cardiovascular disorder;

   7. QT interval corrected for heart rate (QTcF) prolongation at baseline, defined as an average of three consecutive ECG measurements during screening of >470 ms for females and >450 ms for males, or a history of long QT syndrome ;

   8. Hepatic cirrhosis of Child-Pugh Class B or worse; or any degree of hepatic cirrhosis with a history of hepatic encephalopathy.

4. History of Infectious Diseases:

   1. Severe infection within 4 weeks prior to the first dose;
   2. Any confirmed active HIV, HBV or HCV infection.

5. Other Conditions:

   1. Pregnant or breastfeeding women;
   2. Known, documented, or suspected drug abuse;
   3. In the investigator's opinion, the participant is unsuitable for participation in this study for other reasons.