Autologous CD30.CAR-T in Combination With Nivolumab in cHL Patients After Failure of Frontline Therapy (ACTION)

Phase 1b Study Evaluating the Safety and Efficacy of Autologous CD30.CAR-T in Combination With PD-1 Checkpoint Inhibitor (Nivolumab) in Relapsed or Refractory Classical Hodgkin Lymphoma Patients After Failure of Frontline Therapy (ACTION)

This is a Phase 1b, multicenter, open-label, single arm study to evaluate the safety and efficacy of the combination therapy, CD30.CAR-T and the programmed cell death protein-1 (PD-1) checkpoint inhibitor, nivolumab, in patients aged 12 years of age and above with relapsed or refractory classical Hodgkin lymphoma (cHL) following failure of standard frontline therapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Classical Hodgkin Lymphoma; Hodgkin Disease Recurrent; Hodgkin Disease Refractory
• Intervention / Treatment: Drug: Nivolumab; Drug: Autologous CD30.CAR-T; Drug: Fludarabine; Drug: Bendamustine

Detailed Description

Upon successful leukapheresis to produce CD30.CAR-T cells, patients will enter the treatment phase of the study. Treatments will include 4 cycles of nivolumab and CD30.CAR-T infusion (preceded by lymphodepletion chemotherapy). Patients will then enter the post-treatment follow-up phase of the study, whereby patients will undergo either autologous stem cell transplant or continue to receive up to 6 additional treatment cycles of nivolumab. Patients will be followed for response assessments and safety monitoring until end of study (EOS); approximately 3 years after leukapheresis. Long-term follow-up will continue with additional safety monitoring and survival for up to 15 years after Leukapheresis.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Trials Tessa; Phone Number: +65 63840755; Email: clinicaltrials@tessacell.com

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Lineberger Comprehensive Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed ICF
2. Male or female patients who are 12 years of age and above
3. Relapsed or refractory CD30+ cHL following failure of a standard frontline chemotherapy
4. At least 1 lesion, which must be fluordeoxyglucose positron emission tomography (FDG-PET) avid and measurable by PET-CT scan
5. Adequate laboratory parameters including hematologic, renal, hepatic, and coagulation function
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1, or equivalent either Karnofsky performance status (for patients ≥ 16 years of age) or Lansky performance status (for patients < 16 years of age)
7. Anticipated life expectancy > 12 weeks
8. No active infections including COVID 19 at Screening

Exclusion Criteria:

1. Evidence of lymphomatous involvement of the central nervous system (CNS)
2. Presence of clinically relevant or active seizure disorder, stroke, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with central nervous system (CNS) involvement
3. Symptomatic cardiovascular disease: Class III or IV according to the New York Heart Association (NYHA) Functional Classification
4. Active uncontrolled bleeding or a known bleeding diathesis
5. Inadequate pulmonary function defined as oxygen saturation by pulse oximetry < 90% on room air
6. Echocardiogram (ECHO) or Multi-gated Acquisition (MUGA) scan with left ventricular ejection fraction (LVEF) < 45%
7. Prior receipt of salvage therapy, for relapsed or refractory cHL, including allogeneic or ASCT
8. Prior receipt of investigational CD30.CAR-T cells
9. Receiving any investigational agents or any tumor vaccines
10. Receiving any live/attenuated vaccines
11. Ongoing treatment with immunosuppressive drugs or chronic systemic corticosteroids
12. Unresolved > Grade 1 non-hematologic toxicity associated with any prior treatments
13. Previous history of known or suspected autoimmune disease within the past 5 years
14. Active interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
15. Evidence of human immunodeficiency virus (HIV) infection
16. Evidence of active viral infection with hepatitis B virus (HBV)
17. Evidence of active viral infection with hepatitis C virus (HCV)
18. Active second malignancy or history of another malignancy within the last 3 years
19. History of hypersensitivity reactions to murine protein-containing products or other product excipients
20. Any allergic or adverse reaction to nivolumab, fludarabine, or bendamustine that precludes treatment with these agents
21. History of a significant irAE from prior immune checkpoint inhibitor therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nivolumab and CD30.CAR-T; Study treatment will include 4 cycles of nivolumab and a single CD30.CAR-T infusion (preceded by lymphodepletion chemotherapy of Fludarabine and Bendamustine).	Drug: Nivolumab; Dose: 480 mg or 6 mg/kg Q4W; Other Names: Opdivo; Drug: Autologous CD30.CAR-T; Dose: 2 x 10e8 cells/m2; Other Names: CD30-directed CAR-T cells; Drug: Fludarabine; Dose: 30 mg/m2/day x 3 days; Other Names: Fludara; Drug: Bendamustine; Dose: 70 mg/m2/day x 3 days; Other Names: Treanda; Bendeka

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of autologous CD30.CAR-T in combination with nivolumab	DLT	From first dose of nivolumab (Cycle 1) to end of nivolumab Cycle 4 (each cycle is 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-tumor activity using CR rate of autologous CD30.CAR-T in combination with nivolumab	CR rate	Up to end of 10 weeks post-CD30.CAR-T treatment
Overall response rate	ORR	Through study completion, an average of 3 years from Leukapheresis
Duration of response	DOR	Through study completion, an average of 3 years from Leukapheresis
Progression-free survival	PFS	Through study completion, an average of 3 years from Leukapheresis

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	OS	Through study completion, an average of 3 years from Leukapheresis
Pharmacokinetics - Maximum concentration (Cmax)	Maximum concentration of CD30.CAR-T	Through study completion, an average of 3 years from Leukapheresis
Pharmacokinetics - Time of maximum concentration (Tmax)	Time to peak concentration of CD30.CAR-T in the blood	Through study completion, an average of 3 years from Leukapheresis
Pharmacokinetics - Area under the curve	Area under the curve of CD30.CAR-T in the blood	Through study completion, an average of 3 years from Leukapheresis

Collaborators and Investigators

• Sponsor: Tessa Therapeutics
• Collaborators: Bristol-Myers Squibb
• Investigators: Principal Investigator: Sairah Ahmed, MD, M.D. Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2022
• Primary Completion (Anticipated): December 15, 2025
• Study Completion (Anticipated): December 15, 2037

Study Registration Dates

• First Submitted: April 8, 2022
• First Submitted That Met QC Criteria: April 24, 2022
• First Posted (Actual): April 29, 2022

Study Record Updates

• Last Update Posted (Actual): April 3, 2023
• Last Update Submitted That Met QC Criteria: March 31, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: cHL
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Bendamustine Hydrochloride; Fludarabine
• Other Study ID Numbers: TESSCAR003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No