Study of GC012F, CAR-T Therapy Targeting CD19 and BCMA in Chinese Participants With Relapsed or Refractory AL Amyloidosis

A Phase 1b Study of GC012F, a Chimeric Antigen Receptor T Cell Therapy Targeting CD19 and B-cell Maturation Antigen in Chinese Participants With Relapsed or Refractory AL Amyloidosis

This is a Phase 1b open-label, multicenter, non-randomized study of GC012F, a CD19/BCMA dual CAR T cell therapy, in adult participants with relapsed/refractory AL amyloidosis.

This is a Phase 1b, open-label, multicenter, non-randomized study to evaluate the safety, tolerability, and efficacy of GC012F in adult participants with relapsed/refractory AL amyloidosis. A single-arm design was chosen for the study due to the absence of approved therapies for use as a concurrent control for this patient population. In the study, the safety of different doses of GC012F will be evaluated and the RP2D will be selected based on the totality of clinical safety, preliminary efficacy, CK and PD data.

Inclusion Criteria:

1. Confirmed histopathological diagnosis of AL amyloidosis
2. One or more organs currently or historically impacted by AL amyloidosis according to consensus guidelines
3. Measurable hematologic disease: dFLC > 20 mg/L or serum M-protein > 5g/L
4. Relapsed disease or refractory disease defined as a need for additional therapy after at least 1 line of anti-plasma cell-directed therapy.
5. ECOG performance status of 0 to 1
6. Must be able and willing to adhere to the study visit schedule and other protocol requirements
7. Women of child-bearing potential (WCBP) must have a negative serum pregnancy test prior to treatment. All sexually active WCBP and all sexually active male subjects must agree to use effective methods of birth control throughout the study.

Exclusion Criteria:

1. Have any other form of amyloidosis other than AL amyloidosis

2. Mayo Stage IIIb AL amyloidosis

3. Oxygen saturation < 95% on room air

4. Systolic blood pressure <100mmHg

5. Cardiac exclusion criteria:

   1. Mayo Stage IIIb AL amyloidosis as defined by

      - NT-proBNP>8500ng/L, and

      • high sensitivity cardiac troponin T ≥ 50 ng/L cardiac Troponin T ≥ 0.035 ng/mL or cardiac Troponin I ≥ 0.1 ng/mL

   2. NT-proBNP levels as follows:

      - NT-proBNP ≥ 2000 ng/L (for dose escalation portion)

      • NT-proBNP < 2000 and > 8500 ng/L (for dose extension portion)

   3. NYHA class III or IV

5. Extensive GI involvement with evidence of active GI bleeding/risk of bleeding as determined by Investigator 6. Prior therapies:

1. CAR T cell therapy directed at any target
2. Prior BCMA-targeting therapy
3. Prior treatment with any approved or investigational T cell engaging therapies (including T cell-directed bispecific or trispecific therapies) at any target within the last 6 months.

7. Toxicity from previous anti-cancer or anti-PC-directed therapy did not resolve to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy.

8. Active plasma cell leukemia at the time of screening 9. Multiple myeloma defined as clonal bone marrow PCs ≥10% and any one or more of the following myeloma defining events (deemed as attributable to multiple myeloma by Investigator) 10. Seropositive for HIV 11. Serologic status reflecting active hepatitis B or C:

1. Positive HBsAg, or
2. Patients with positive core antibody (anti-HBc) and HBV-DNA positive.
3. Patients with positive hepatitis C antibody and HCV RNA positive.