GC012F dual CD19/BCMA CAR-T therapy for adults with relapsed or refractory AL amyloidosis in China

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 study will try a dual-target CAR-T treatment called GC012F in Chinese adults whose AL amyloidosis has come back or not responded to previous therapies.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 9 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Gracell Biotechnologies (Shanghai) Co., Ltd. (Industry-sponsored)
• Drugs / interventions: CAR T
• Locations: 9 sites (Beijing and 8 other locations)
• Trial ID: NCT07250269 on ClinicalTrials.gov

What this trial studies

This Phase 1b, open-label, multicenter, single-arm study gives escalating doses of GC012F — a CAR-T product targeting both CD19 and BCMA — to adults with relapsed or refractory AL amyloidosis to characterize safety and select a recommended Phase 2 dose. Participants are treated at several sites in Beijing and followed for safety, hematologic response (dFLC, M-protein), pharmacodynamic and pharmacokinetic markers, and organ function. A single-arm design was chosen because there are no approved therapies suitable as concurrent controls for this population. Dose selection will be based on the totality of clinical safety, preliminary efficacy, and biomarker data.

Who should consider this trial

Good fit: Adults in China with histologically confirmed AL amyloidosis, measurable hematologic disease (dFLC > 20 mg/L or serum M-protein > 5 g/L), relapsed or refractory after at least one prior anti-plasma-cell therapy, ECOG 0–1, and able to attend Beijing study visits are ideal candidates.

Not a fit: Patients with other types of amyloidosis, Mayo Stage IIIb cardiac disease, oxygen saturation <95% on room air, systolic blood pressure <100 mmHg, or significant comorbidities are excluded and unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, GC012F could produce deep blood-level remissions and lead to recovery of organ function for patients with relapsed or refractory AL amyloidosis.

How similar studies have performed: CAR-T therapies targeting BCMA and CD19 have produced high response rates in multiple myeloma and early case reports and small series suggest potential activity in AL amyloidosis, but large-scale controlled data in AL are limited.

Eligibility criteria

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 (Wechalekar, 2013)
   2. NT-proBNP levels as follows:

NT-proBNP ≥ 2000 ng/L (for dose escalation portion) NT-proBNP \< 2000 and \> 5000 ng/L (for dose extension portion) c. High-sensitivity cardiac troponin T \> 75 ng/L d. 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) (Rajkumar, 2014) 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.

Where this trial is running

Beijing and 8 other locations

• Research Site — Beijing, China (Recruiting)
• Research Site — Beijing, China (Recruiting)
• Research Site — Beijing, China (Recruiting)
• Research Site — Changchun, China (Recruiting)
• Research Site — Guangzhou, China (Recruiting)
• Research Site — Hangzhou, China (Not_yet_recruiting)
• Research Site — Suzhou, China (Recruiting)
• Research Site — Wenzhou, China (Recruiting)
• Research Site — Wuhan, China (Not_yet_recruiting)

Study contacts

• Study coordinator: AstraZeneca Clinical Study Information Center

Conditions Relapsed/Refractory AL Amyloidosis