QUADvance: Advancing Allogeneic Quad-CAR01-T Therapy in Hard-to-Treat B-Cell Cancers

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Avencell Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

15 Dec 2025 → ongoing

Decision date (initial)

2025-10-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AvenCell Therapeutics Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacokinetic, Efficacy, Dose response, Safety, Pharmacodynamic

Phase Ia: To assess the safety and tolerability of different dose levels of Allo-QuadCAR01-T
Phase Ib: To assess the safety and tolerability of Allo-QuadCAR01-T and confirm the recommended Phase 2 dose (RP2D) of Allo-QuadCAR01-T
Phase II: To evaluate the clinical efficacy of Allo-QuadCAR01-T

Secondary objectives 18

1. Phase Ia: To determine the overall safety profile of Allo-QuadCAR01-T
2. Phase Ia: To evaluate the clinical efficacy of Allo-QuadCAR01-T
3. Phase Ia: To investigate pharmacokinetics (PK) of Allo-QuadCAR01-T in peripheral blood (PB) in patients after infusion of Allo-QuadCAR01-T
4. Phase Ia: To investigate the impact of Allo-QuadCAR01-T on measurable residual disease (MRD)
5. Phase Ia: To evaluate immunogenicity against Allo-QuadCAR01-T
6. Phase Ia: To evaluate host immune cell depletion and reconstitution resulting from lymphodepletion (LD)
7. Phase Ib: To evaluate the clinical efficacy of Allo-QuadCAR01-T
8. Phase Ib: To further evaluate the clinical efficacy of Allo-QuadCAR01-T
9. Phase Ib: To investigate PK of Allo-QuadCAR01-T in PB in patients after infusion of Allo-QuadCAR01-T
10. Phase Ib: To investigate the impact of Allo-QuadCAR01-T on MRD
11. Phase Ib: To evaluate immunogenicity against Allo-QuadCAR01-T
12. Phase Ib: To evaluate host immune cell depletion and reconstitution resulting from LD
13. Phase II: To assess the safety and tolerability of Allo-QuadCAR01-T
14. Phase II: To further evaluate the clinical efficacy of Allo-QuadCAR01-T
15. Phase II: To investigate PK of Allo-QuadCAR01-T in PB in patients after infusion of Allo-QuadCAR01-T
16. Phase II: To investigate the impact of Allo-QuadCAR01-T on MRD
17. Phase II: To evaluate immunogenicity against Allo-QuadCAR01-T
18. Phase II: To evaluate host immune cell depletion and reconstitution resulting from LD

Conditions and MedDRA coding

Relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL) or chronic lymphocytic leukaemia (CLL)

Regulatory references

Scientific advice from competent authorities

Paul-Ehrlich-Institut

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. 1. Male or female, ≥ 18 years old.
2. 2. Willing and able to give written informed consent.
3. 3. Have histologically confirmed R/R B-NHL or CLL, per WHO classification, expected to express CD19 and/or CD20, have received, deemed ineligible for, or have declined standard therapies reimbursed by their health care system, have received a minimum of 2 treatment lines, and have a clinical need for systemic treatment. • Large B-cell lymphoma (LBCL) (including e.g., diffuse large B-cell lymphoma (DLBCL), High-grade BCL (HGBL), transformed LBCL from indolent lymphoma or CLL, Primary mediastinal large B-cell lymphoma (PMBCL) – but not primary CNS lymphoma (PCNSL)) • Follicular lymphoma (FL) • Marginal zone lymphoma (MZL) • Mantle cell lymphoma (MCL) • Chronic lymphocytic leukemia/Small lymphocytic leukemia (CLL/SLL)
4. 4. For lymphomas (including SLL), measurable disease with at least 1 bi-dimensional measurable lesion (CT/MRI), longest diameter > 1.5 cm for nodal, > 1 cm for extra-nodal within a month of the treatment start, and after any anti-lymphoma therapies. Previously radiated lesions are eligible only if there is documented progression on the site after radiation therapy. Only MRD positivity is not considered eligible.
5. 5. For CLL, indication for treatment per iwCLL 2018 guideline and objectively measurable disease (e.g., lymphocytosis or measurable lesion, including lymphadenopathy, splenomegaly, and extra-nodal lesions, but not e.g., autoimmune manifestations only, or MRD positivity).
6. 6. Fresh or archival biopsy sample available (obtained after last systemic treatment line), or willingness to provide one for retrospective CD19/CD20 expression analysis. A patient may be included without biopsy material with Sponsor approval if the biopsy procedure would cause unacceptable safety risk or discomfort.
7. 7. HLA B and C types match 1 or more of the available IMP batches.
8. 8. ECOG 0 to 1.
9. 9. Adequate organ function: • Calculated CrCl ≥ 60 mL/min Note: CrCl must be calculated using the Cockcroft-Gault Method: CrCl = ((140 – age) × weight)/(72 × SCr)) [× 0.85 (if female)] CrCl = mL/minute; Age = years; Weight = kg; SCr = mg/dL • Direct bilirubin ≤ 1.5 × ULN (unless Gilbert’s syndrome) • AST/ALT ≤ 2.5 × ULN (up to 5 × ULN if elevation directly caused by lymphoma infiltration) • LVEF ≥ 45% (per local standard method, e.g., transthoracic echocardiography) • Oxygen saturation ≥ 92% on room air • Blood counts: - ANC ≥ 1.0 × 10^9 L (≥ 0.75 × 10^9 /L may be eligible with Sponsor approval) - Platelets ≥ 50 × 10^9 /L - Hb ≥ 7 g/dL Note: Lower levels may be allowed after Sponsor approval if cytopenia directly caused by lymphoma/CLL infiltration.
10. 10. Life expectancy of ≥ 3 months as assessed by the Investigator.
11. 11. Central venous access or willingness to have one.
12. 12. Weight is greater than the minimum weight required for a specific batch to ensure that the dose administered does not exceed 10^5 TCR+ cells/kg of patient weight.
13. 13. A woman of childbearing potential (WOCBP) may be enrolled if she has a negative serum pregnancy test at Screening visit and is willing to use a highly effective method of birth control (Pearl index of ≤ 1 required) resulting in a low failure rate (e.g., hormonal contraception, intrauterine device, total sexual abstinence, or sterilization) for at least 12 months after LD chemotherapy. Male patients must also practice a highly effective method of birth control and should not father a child or donate sperm for at least 6 months after end of LD chemotherapy.

Exclusion criteria 24

1. 1. Active CNS involvement (including PCNSL) is excluded from dose escalation cohorts. However, these individuals may be enrolled to established safe dose cohorts (i.e., backfill cohorts, dose expansion) with Sponsor approval.
2. 10. Active viral infection within 1 week of Screening or ongoing bacterial or fungal infection requiring hospitalization or intravenous antimicrobials, or any other ongoing infection that would have a significant impact on safety or trial conduct per Investigator or Sponsor judgement.
3. 11. Presence of hemorrhagic cystitis.
4. 12. Active neuro-autoimmune diseases, including MS, Guillain-Barré, ALS.
5. 2. Prior CAR-T treatment within 3 months of Screening, or ≥ Grade 3 ICAHT associated with prior CAR-T treatment. Note: ICAHT per EHA/EBMT recommendation, Grade 3: ANC ≤ 0.1 × 10^9 /L for 7 days, or ANC ≤ 0.5 × 10^9 /L for 14 days, or ANC ≤ 0.5 × 10^9 /L 30 days after the CAR-T administration or later.
6. 3. Hematological autologous hematopoietic stem cell transplantation within 3 months.
7. 4. Prior allogeneic hematopoietic stem cell transplantation or solid organ transplant.
8. 5. Prior therapy with dual CD19/CD20 targeting CAR-T.
9. 6. Known severe hypersensitivity reaction attributed to compounds of similar chemical or biologic composition to any agents used in trial.
10. 7. History of graft versus host disease (GvHD) or post-transplant lymphoproliferative disorder.
11. 8. Presence of autoantibodies against La/SS-B or presence or history of autoimmune diseases associated with such antibodies.
12. 9. History of other malignancy that could affect compliance with the protocol or interpretation of results, excluding: • History of curatively treated basal or squamous cell carcinoma of the skin, or in situ carcinoma of the cervix at any time prior to Screening. • Low-grade, early-stage prostate cancer (Gleason score ≤ 6, Stage 1 or 2) with no requirement for therapy at any time prior to Screening. • Current adjuvant endocrine therapy for non-metastatic, hormone receptor-positive breast cancer for 2 or more years prior to Screening. • Any other malignancy treated with curative intent and in remission without treatment for 2 years prior to Screening.
13. 13. Active or residual HBV, HCV, or syphilis.
14. 14. Active HIV disease. Individuals with positive HIV history may be included with Sponsor approval after Phase Ia dose escalation if: • Ongoing antiretroviral treatment for ≥ 6 months • Adherence to antiretroviral treatment per Investigator judgement and leading to good treatment response • Good treatment response, defined by absence of clinical symptoms (including infectious and constitutional), normal blood CD4+ count (at least 500 cells /μL), and undetected HIV RNA (≤ 50 copies /mL).
15. 15. Active or recent (within 6 months of Screening) cerebrovascular ischemia/hemorrhage, dementia, Parkinson’s disease, cerebellar disease, or autoimmune disease with CNS involvement that may impair ability to evaluate neurotoxicity or have an impact on trial safety per Sponsor or Investigator assessment.
16. 16. History of MI, cardiac angioplasty or stenting, unstable angina or other clinically significant cardiac disease within 6 months of Screening with an impact on trial safety per Sponsor or Investigator assessment.
17. 17. Primary immunodeficiency or history of autoimmune disease (e.g., Crohn’s disease, rheumatoid arthritis, systemic lupus) requiring systemic treatment within 1 year of Screening unless stable and not increasing safety risk per Investigator judgement and approved by the Sponsor.
18. 18. Other non-hematological toxicity from prior anti-cancer treatment that has not resolved to Grade ≤1 or baseline, except for peripheral neuropathy which is eligible up to Grade 2.
19. 19. Systemic immunosuppression within 28 days of Screening.
20. 20. Last systemic lymphoma or CLL treatment, including standard and investigational treatments, within 28 days or within 5 half-lives of Screening, whichever is shorter.
21. 21. Major surgery within 14 days of Screening.
22. 22. Local radiation within 28 days of Screening.
23. 23. Live vaccination within 28 days of Screening.
24. 24. Pregnant or breastfeeding. Note: Any period mentioned before Screening (i.e., within xx days/week “of Screening”) means time before the last day of Screening period (eligibility confirmation date by the Sponsor or delegate).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Phase Ia: Incidence of adverse events (AEs) defined as dose-limiting toxicity (DLTs)
2. Phase Ib: Incidence, type, and severity of all AEs, treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), and serious adverse events (SAEs)
3. Phase II: Complete response rate (CRR) through and including the Week 13 assessment visit

Secondary endpoints 18

1. Phase Ia: Incidence, type and severity of all AEs, TEAEs, TRAEs, and SAEs including DLTs; Define recommended dose(s) for Phase Ib
2. Phase Ia: CRR (including complete response with incomplete hematological recovery (CRi) in chronic lymphocytic leukemia (CLL)) through and including the Week 13 assessment; Duration of response (DOR)
3. Phase Ia: PK parameters of CAR-T (peak expansion, area under the concentration-time curve (AUC), persistence)
4. Phase Ia: MRD levels in responding patients
5. Phase Ia: Incidence of antidrug antibody (ADA)1 formation against anti-CD19/CD20 ECD and ADA2 formation against the RevCAR extracellular domain (ECD) of Allo-QuadCAR01-T
6. Phase Ia: Enumeration of host PB B-cell, T cell, and NK-cell numbers
7. Phase Ib: CRR through and including the Week 13 assessment
8. Phase Ib: • DOR on trial • Partial response rate (PRR) through and including the Week 13 assessment • Overall response rate (ORR) through and including the Week 13 assessment • Progression free survival (PFS) • Time to next treatment (TTNT) • Overall survival (OS)
9. Phase Ib: PK parameters of CAR-T (peak expansion, AUC, persistence)
10. Phase Ib: MRD levels in responding patients
11. Phase Ib: Incidence of ADA1 formation against anti-CD19/CD20 ECD and ADA2 formation against the RevCAR ECD of Allo-QuadCAR01-T
12. Phase Ib: Enumeration of host PB B-cell, T cell, and NK cell numbers
13. Phase II: Incidence, type, and severity of all AEs, TEAEs, TRAEs, and SAEs
14. Phase II: • DOR • PRR through and including the Week 13 assessment visit • ORR through and including the Week 13 assessment visit • PFS • TTNT • OS
15. Phase II: PK parameters of CAR-T (peak expansion, AUC, persistence)
16. Phase II: MRD levels in responding patients
17. Phase II: Incidence of ADA1 formation against anti-CD19/CD20 ECD and ADA2 formation against the RevCAR ECD of Allo-QuadCAR01-T
18. Phase II: Enumeration of host PB B-cell, T cell, and NK cell numbers

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Avencell Therapeutics Inc.

Sponsor organisation

Avencell Therapeutics Inc.

Address

500 Forge Road Suite 320

City

Watertown

Postcode

02472-2266

Country

United States

Scientific contact point

Organisation

Avencell Therapeutics Inc.

Contact name

CMO

Public contact point

Organisation

Avencell Therapeutics Inc.

Contact name

Clinical Trial Manager

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications