NK cell therapy with epcoritamab and tafasitamab for relapsed or treatment‑resistant B‑cell lymphoma

Phase I/II Trial of ONC-PluReceptor NK Cells With Epcoritamab and Tafasitamab for Patients With Recurrent or Refractory B-cell Non-Hodgkin Lymphoma

This trial will try whether adding donor-derived ONC-PluReceptor NK cells to the antibodies epcoritamab and tafasitamab helps control relapsed or refractory CD19/CD20-positive B‑cell non‑Hodgkin lymphoma.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: M.D. Anderson Cancer Center (Academic / other)
• Drugs / interventions: alemtuzumab, CAR-T, Radiation, epcoritamab, tafasitamab
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT07283679 on ClinicalTrials.gov

What this trial studies

This phase 1/2 trial gives umbilical cord‑blood‑derived NK cells engineered with the ONC‑PluReceptor construct together with the monoclonal antibodies epcoritamab and tafasitamab to adults with relapsed or refractory CD19/CD20‑positive B‑cell non‑Hodgkin lymphoma. Phase 1 uses dose escalation to establish safety and the recommended phase II dose, followed by phase 2 to measure response rates and duration of response at that dose. Investigators will monitor for treatment‑related toxicities, track persistence of infused donor NK cells in recipients, and perform detailed immune reconstitution studies. Secondary endpoints include overall and complete response rates, progression‑free survival, and overall survival.

Who should consider this trial

Good fit: Adults aged 18–80 with relapsed or refractory CD19‑ or CD20‑positive diffuse large B‑cell lymphoma or follicular lymphoma who have failed at least two prior therapies (or transplant) and meet organ function and performance‑status requirements are the intended participants.

Not a fit: Patients whose tumors lack CD19/CD20 expression, who have inadequate organ function or performance status, uncontrolled infections, or who cannot travel to the Houston site are unlikely to benefit or to be eligible.

Why it matters

Potential benefit: If successful, the combination could offer a new option that induces remissions in patients whose lymphoma has returned or not responded to multiple prior therapies, including those who cannot receive or failed CAR‑T therapy.

How similar studies have performed: Early‑phase studies of engineered NK cells and of antibodies such as epcoritamab or tafasitamab have shown promising responses in B‑cell lymphomas, but the specific combination of cord‑blood ONC‑PluReceptor NK cells with both antibodies is novel and has limited prior clinical data.

Eligibility criteria

Inclusion Criteria:

1. Patients with R/R DLBCL or FL with all of the following:

   Failure of \>/= 2 prior lines of therapy, or an autologous or allogeneic stem cell transplant.

   Prior failure of CAR-T or not eligible for CAR-T cells.
2. Tumor biopsy positive for CD19 or CD20 at \>/= 1% by immunohistochemistry or flow cytometry.
3. Age 18-80 years.
4. Karnofsky performance status \>/=60%.
5. Absolute neutrophil count \>/=500/mm3 and platelet count \>/=50,000/mm3.
6. Serum creatinine clearance (CrCl) \>/=30 ml/min, estimated using the Cockcroft-Gault equation:

   Estimated creatinine clearance = (140-age \[years\]) x weight (kg) (x Fa) / serum creatinine (mg/dL) x 72 \[a where F=0.85 for females and F=1 for males\].
7. Adequate hepatic function (ALT and/or AST \</=3 x upper limit of normal (ULN); bilirubin and ALP \</=2 x ULN). Patients with cancer involvement of the liver and elevation of ALT, AST, bilirubin, and/or ALP \</= 5 x ULN are eligible, per PI discretion.
8. Adequate pulmonary function with FEV1, FVC and DLCO (corrected for hemoglobin and volume) \>/=50%.
9. Adequate cardiac function with left ventricular ejection fraction \>/=40%, and no uncontrolled arrhythmias or symptomatic cardiac disease.
10. If female of child-bearing potential, she must not be pregnant or breastfeeding and required to have a negative urine or serum pregnancy test prior to enrollment.
11. Female participants of non-childbearing potential must meet at least one of the following criteria:

    i. Postmenopausal (no menses in greater than or equal to 12 consecutive months).

    ii. History of hysterectomy or bilateral salpingo-oophorectomy. iii. Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).

    o Subjects who are of childbearing potential, sexually active, and at risk of pregnancy must agree to use a highly effective method of contraception for the duration of the active treatment and at least 3 months post-completion of the study therapy. See Appendix B. Highly effective methods of contraception include the following:

    iv. Hormonal contraception (i.e., birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

    o Men treated or enrolled in this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of study agent administration. Men who are able to have children must use effective birth control while in the study. If the male participant fathers a child or suspects that he has fathered a child while in the study, he must immediately notify his doctor.
12. Agree to sign the consent to the long-term follow-up protocol PA17-0843 to fulfill the institutional responsibilities to various regulatory agencies

Exclusion Criteria:

1. Lymphoma in CR with no measurable sites of disease.
2. Major surgery \<4 weeks prior to first dose of study drug.
3. Any other severe or uncontrolled disease or condition that might increase the risk associated with study participation.
4. Any other malignancy known to be active, with the exception of treated cervical intra-epithelial neoplasia and non-melanoma skin cancer.
5. Grade \>/= 3 non-hematologic toxicity from prior therapy that has not improved to grade \</= 2.
6. Active hepatitis B, either active carrier (HBsAg +) or viremic (HBV DNA.\>/=10,000 copies/mL, or \>/=2,000 IU/mL), or hepatitis C (detectable viral load by HCV RNA PCR)
7. Active infection requiring parenteral antibiotics.
8. HIV infection.
9. Treatment within prior 2 weeks with any anti-cancer agent, investigational or approved.
10. Active central nervous system (CNS) involvement (untreated parenchymal brain metastasis or positive cytology of cerebrospinal fluid).
11. Life expectancy \</= 6 months.
12. Active and uncontrolled neurological disorder.
13. Patients receiving systemic steroid therapy at the time of enrollment (physiological substitutive doses are allowed), or have received antithymocyte globulin or lymphocyte immune globulin within 14 days of enrollment or alemtuzumab within 28 days of enrollment.
14. Patients receiving immunosuppressive therapy.

Where this trial is running

Houston, Texas

• The University of Texas M. D. Anderson Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Yago Nieto, MD,PHD — M.D. Anderson Cancer Center
• Study coordinator: Yago Nieto, MD,PHD

Conditions Recurrent B-Cell Non-Hodgkin Lymphoma; Refractory B-cell Non-Hodgkin Lymphoma