Epcoritamab + GDP for Non-Hodgkin's Lymphoma

Recruiting at 3 trial locations

Overseen By Allison Lipps

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dipenkumar Modi

Must not be taking: Gemcitabine, Cisplatin, Epcoritamab

Disqualifiers: CNS involvement, Autoimmune disease, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 9 weeks

32 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, you cannot use any standard or experimental anti-large cell lymphoma therapy within 14 days before starting the trial treatment.

What data supports the effectiveness of the drug Epcoritamab + GDP for Non-Hodgkin's Lymphoma?

Research shows that the GDP regimen (gemcitabine, dexamethasone, and cisplatin) is effective for treating relapsed or refractory aggressive non-Hodgkin's lymphoma, with gemcitabine and cisplatin also being effective in some solid tumors. Additionally, cisplatin has shown activity as a single agent in non-Hodgkin's lymphoma. ^{1 2 3 4 5}

What safety data exists for Epcoritamab + GDP treatment in humans?

Cisplatin, a component of the treatment, can cause side effects like nausea, vomiting, and kidney issues, but these often resolve after stopping the drug. Other possible side effects include hearing loss and nerve damage, so careful monitoring is needed during treatment. ^{6 7 8 9 10}

What makes the drug Epcoritamab + GDP unique for treating Non-Hodgkin's Lymphoma?

The combination of Epcoritamab with GDP (Gemcitabine, Cisplatin, and Dexamethasone) is unique because it includes Epcoritamab, a novel bispecific antibody that targets CD3 and CD20, potentially enhancing the immune system's ability to attack lymphoma cells, which is different from traditional chemotherapy approaches. ^{3 11 12 13 14}

What is the purpose of this trial?

Subjects with relapsed large cell lymphoma will receive 3 cycles of combination therapy consisting of GDP and epcoritamab. Each cycle will last 21 days. GDP consists of gemcitabine 1000 mg/m2 IV on Days 1 and 8, cisplatin 75 mg/m2 IV on Day 1, and dexamethasone 40 mg orally on Days 1 through 4. Epcoritamab will be administered subcutaneously (SC) on Days 1, 8, and 15. Patients will receive granulocyte colony stimulating factor (G-CSF) between Day 8 through Day 10 of each cycle of combination therapy. Patients will then undergo radiology imaging for disease assessment. Patients may proceed to SCT(autologous or allogeneic) or CAR T-cell therapy or epcoritamab monotherapy upon completion of Cycle 3 per investigator discretion. The rationale for subjects not proceeding to autoSCT or CAR T-cell therapy will be captured in the eCRFs. Patients who do not undergo SCT or CAR T-cell therapy may have the option to receive study treatment with epcoritamab monotherapy following completion of Cycle 3. Epcoritamab monotherapy will be offered to selected subjects who become ineligible to undergo SCT or CAR T-cell therapy (such as social situation, change in subject decision). The decision to offer epcoritamab monotherapy will be per investigator's discretion. However, subjects must have demonstrated a response to the combination therapy (partial remission or complete remission) per disease assessment scans prior to offering epcoritamab monotherapy. Epcoritamab monotherapy should begin 2 weeks following Cycle 3 Day 15. Monotherapy will consist of epcoritamab 48 mg administered subcutaneously on Days 1 and 15 of each 28 day cycle for Cycle 4 to Cycle 9 or until unacceptable toxicity, or disease progression per the Lugano Criteria.

Research Team

Dipenkumar Modi, MD

Principal Investigator

Wayne State University

Eligibility Criteria

Adults over 18 with CD20+ relapsed large cell lymphoma, who've had at least one prior systemic therapy and are eligible for high dose chemotherapy and stem cell transplant. They must have measurable disease, adequate organ function, a life expectancy of more than 6 months, and agree to use contraception. HIV-positive patients can join if treated; those with hepatitis B or C must meet specific criteria.

Inclusion Criteria

I can understand and follow the study's procedures for its duration.

My lymphoma has returned and tests show it is CD20 positive.

I have been mostly active and able to care for myself in the last 28 days.

Exclusion Criteria

I have moderate to severe nerve pain or numbness.

I do not have any current infections or significant infections in the last 2 weeks.

Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the subject's safety, or being compliant with the study procedures

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 3 cycles of combination therapy consisting of GDP and epcoritamab. Each cycle lasts 21 days.

9 weeks

3 visits per cycle (in-person)

Radiology Imaging

Patients undergo radiology imaging for disease assessment after completion of Cycle 3.

1 week

Epcoritamab Monotherapy

Epcoritamab monotherapy is offered to selected subjects who become ineligible for SCT or CAR T-cell therapy, starting 2 weeks after Cycle 3 Day 15.

6 months

2 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment.

4 years

Treatment Details

Interventions

• Cisplatin
• Epcoritamab
• Gemcitabine

Trial Overview The trial tests Epcoritamab combined with GDP (gemcitabine, dexamethasone, cisplatin) chemotherapy in three cycles for treating relapsed large cell lymphoma. Afterward, patients may receive autoSCT/CAR T-cell therapy or continue epcoritamab alone based on the doctor's discretion.

Participant Groups

Group I: GDP + Epcoritamab + Epcoritamab Maintenance Experimental Treatment 2 Interventions

Cycles 1-3 (Cycle = 21 days) Epcoritamab will be administered by subcutaneous injection Days 1, 8, and 15 of each Cycle. Epcoritamab Day 1: 0.16mg, Day 8: 0.8mg, Day 15: 48mg except Cycle 2-Epcoritabab will administered at 48mg on Days 1, 8 and 15 Gemcitabine will be administered by IV infusion on Days 1 and 8 of each Cycle. Gemcitabine Days 1,8: 1,000mg/m\^2 Cisplatin will be administered by IV infusion on Day 1 of each Cycle. Cisplatin Day 1: 75mg/m\^2 Dexamethasone will be given by mouth on Days 1-4 of Cycle 1 ONLY. Dexamethasone Days 1-4: 40mg Cycles 4-9 (Cycle =28 Days) Epcoritamab will be administered by subcutaneous injection on Days 1, 8, and 15 of Cycles 4-9.

Group II: GDP + Epcoritamab + AutoSCT or CAR T-cell therapy Experimental Treatment 3 Interventions

Cycles 1-3 (Cycle = 21 days) Epcoritamab will be administered by subcutaneous injection Days 1, 8, and 15. Epcoritamab Day 1: 0.16mg, Day 8: 0.8mg, Day 15: 48mg except Cycle 2-Epcoritamab will administered at 48mg on Days 1, 8 and 15 Gemcitabine will be administered by IV infusion on Days 1 and 8. Gemcitabine Days 1,8: 1,000mg/m\^2 Cisplatin will be administered by IV infusion on Day 1. Cisplatin Day 1: 75mg/m\^2 Dexamethasone will be given by mouth on Days 1-4. Dexamethasone Days 1-4: 40mg After completion of Cycle 3 Autologous stem cell transplant (AutoSCT) OR CAR T-cell therapy

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

Dipenkumar Modi

Lead Sponsor

Trials

1

Recruited

30+

Genmab

Industry Sponsor

Trials

76

Recruited

15,300+

Dr. Jan van de Winkel

Genmab

Chief Executive Officer since 2010

PhD in Immunology, University of Utrecht

Dr. Judith Klimovsky

Genmab

Chief Medical Officer since 2019

MD, University of Copenhagen

Findings from Research

The GDP regimen (gemcitabine, dexamethasone, and cisplatin) demonstrated a 58.3% overall response rate in 24 patients with relapsed or refractory aggressive non-Hodgkin's lymphoma, indicating its efficacy as a salvage treatment.

The treatment was relatively well-tolerated, with no treatment-related deaths and mild non-hematologic toxicities, although 37.5% of patients experienced severe leucopenia, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of GDP regimen (gemcitabine, dexamethasone, and cisplatin) on relapsed or refractory aggressive non-Hodgkin's Lymphoma: a report of 24 cases]. Fan, Y., Huang, ZY., Luo, LH., et al.[2015]

The combination of gemcitabine, dexamethasone, and cisplatin (GDP) showed a promising overall response rate of 49% in patients with recurrent or refractory non-Hodgkin lymphoma, with 16% achieving complete responses after two treatment cycles.

Despite some significant toxicities, such as grade 3 and 4 neutropenia in 33% and 39% of patients respectively, the GDP regimen can be safely administered to outpatients, allowing many patients to proceed to stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine, dexamethasone, and cisplatin in patients with recurrent or refractory aggressive histology B-cell non-Hodgkin lymphoma: a Phase II study by the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG). Crump, M., Baetz, T., Couban, S., et al.[2022]

In a phase II study, cis-dichlorodiammineplatinum(II) (CDDP) demonstrated activity as a single agent in treating non-Hodgkin's lymphoma, with 3 out of 10 patients achieving partial remission lasting 7-15 weeks.

The combination of CDDP with ICRF-159 was not effective, as none of the 8 patients treated with this combination achieved an objective response, indicating it may not be a viable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

cis-dichlorodiammineplatinum(II) with and without ICRF-159 in non-Hodgkin's lymphoma. Corder, MP., Wiesenfeld, M., Maguire, LC., et al.[2013]

In a study of 69 patients with relapsed and refractory Hodgkin and Non-Hodgkin lymphoma, the GDP/R-GDP regimen effectively mobilized CD34+ stem cells in 98% of chemosensitive patients, allowing them to proceed to autologous stem cell transplantation.

The treatment demonstrated low toxicity, making it suitable for outpatient settings, and was particularly effective in patients with early-stage disease, suggesting its potential as a preferred option for stem cell mobilization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine, dexamethasone and cisplatin (GDP) is an effective and well-tolerated mobilization regimen for relapsed and refractory lymphoma: a single center experience Batgi, H., Başcı, S., Dal, MS., et al.[2022]

In a study involving 557 patients with advanced non-small-cell lung cancer (NSCLC), the combination of cisplatin and gemcitabine (CG) showed significantly better response rates compared to nonplatinum sequential doublets, with response rates of 42% for CG versus 27% for GV-VI.

While the triplet regimen (CGV) had higher toxicity rates, including increased instances of severe neutropenia and thrombocytopenia, the median survival and time to progression were similar across all treatment groups, supporting CG as a standard first-line treatment for advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin plus gemcitabine versus a cisplatin-based triplet versus nonplatinum sequential doublets in advanced non-small-cell lung cancer: a Spanish Lung Cancer Group phase III randomized trial. Alberola, V., Camps, C., Provencio, M., et al.[2022]

In a Phase I study involving 40 patients with urologic and gynecologic cancers, cis-diamminedichloroplatinum(II) (CIS-DDP) was found to have manageable side effects, primarily nausea, vomiting, and anorexia, which resolved quickly after stopping the treatment.

The study indicated low levels of hematopoietic and renal toxicities, with no reported cases of hearing disturbances or tinnitus, suggesting a favorable safety profile for CIS-DDP at doses of 50 mg/m2 for single administration and 20 mg/m2/day for five consecutive days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Phase I study of a new antineoplastic agent, cis-diamminedichloroplatinum (II)]. [2013]

Cis-dichlorodiammineplatinum(II) can cause serious side effects such as nephrotoxicity, gastrointestinal issues (like nausea and vomiting), and myelosuppression, highlighting the need for careful monitoring during treatment.

Other potential side effects include ototoxicity (which can lead to hearing loss), anaphylactic reactions, and peripheral neuropathies, indicating that while the drug may be effective, its safety profile requires close attention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxic effects of cis-dichlorodiammineplatinum(II) in man. Von Hoff, DD., Schilsky, R., Reichert, CM., et al.[2022]

In a Phase II study involving 77 patients with urologic malignancies, cis-diaminedichloroplatinum(II) (CIS-DDP) demonstrated significant efficacy, with overall response rates of 73.3% for testicular tumors and 50.0% for bladder tumors, indicating its potential as an effective treatment option.

However, the treatment was associated with considerable adverse effects, including gastrointestinal issues in 78.5% of patients, as well as myelosuppression and renal dysfunction, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Phase II study on cis-diamminedichloroplatinum (II) by a collaborative study]. [2013]

CI-973 shows promising efficacy in preclinical models, demonstrating activity comparable or superior to cisplatin and carboplatin, and is effective against cisplatin-resistant cancer cell lines.

In a phase I trial with 28 patients, CI-973 exhibited a favorable safety profile with no renal or auditory toxicity, although mild to moderate nausea and vomiting were common; the maximum tolerated dose was determined to be 290 mg/m2 for patients with good performance status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I clinical evaluation of [SP-4-3(R)]-[1,1-cyclobutanedicarboxylato(2-)](2-methyl-1,4- butanediamine-N,N1) platinum in patients with metastatic solid tumors. Theriault, RL., Cohen, IA., Esparza, L., et al.[2019]

A phase II trial of cisdiammino-dichloro platinum (CDDP) showed significant effectiveness against testis embryonic carcinoma, ovarian carcinoma, and epidermoid cancers, particularly in head and neck and cervical cancers.

While CDDP demonstrates strong anti-cancer activity, it is associated with notable toxicity primarily affecting the digestive and renal systems, leading to its use in combination therapies for the indicated tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cis-diammino-dichloro-platinum therapy of cancers; phase II therapeutic trial]. Hayat, M., Bayssas, M., Brulé, G., et al.[2013]

In a study involving 25 patients with advanced Hodgkin's disease and non-Hodgkin's lymphoma, cis-dichlorodiammineplatinum(II) showed limited efficacy, resulting in one complete response and two partial responses, indicating it may have some therapeutic potential.

The treatment was associated with significant myelosuppression, particularly leukopenia and thrombocytopenia, which were more severe than in previous studies, likely due to the patients' extensive prior treatments and the presence of tumor-bearing marrow.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II evaluation of cis-dichlorodiammineplatinum(II) in lymphomas: a Southwest Oncology Group Study. Rossof, AH., Coltman, CA., Jones, SE., et al.[2013]

The combination of carboplatin and cyclophosphamide is emerging as the preferred treatment for epithelial ovarian cancer due to its effectiveness and lower toxicity compared to cisplatin plus cyclophosphamide, based on several prospective studies.

Current clinical trials are exploring high-dose carboplatin regimens and combinations with other treatments, showing promise in improving survival rates for patients with advanced ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Recent advances in ovarian cancer chemotherapy]. Hatae, M., Onishi, Y., Kume, H., et al.[2018]

Cis-diamminedichloroplatinum(II) (cis-DDP) is a highly effective antineoplastic agent, particularly against non-seminomatous testicular cancer, bladder cancer, and head and neck tumors, with mild myelosuppression allowing for combination therapies.

Despite its potential for nephrotoxicity, this side effect can be managed through forced diuresis, making cis-DDP a viable option for combination chemotherapy in treating various cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cis-diamminedichloroplatinum(II). A new antineoplastic agent derived from the group of heavy metal complexes (author's transl)]. Osieka, R., Schmidt, CG.[2019]

Cis-diamminedichloroplatinum (DDP) has shown strong efficacy against germinal tumors of the testis and promising results in various epithelial cancers, including ovarian and bladder cancers, based on renewed clinical interest and research.

Recent advancements, such as induced diuresis to reduce nephrotoxicity and the identification of safer dosing strategies, suggest that DDP could have a significant future role in cancer treatment, although further investigation into its clinical potential and mechanisms of action is still needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platinum complexes in cancer chemotherapy. [2013]

References

1. China pubmed.ncbi.nlm.nih.gov

[Efficacy of GDP regimen (gemcitabine, dexamethasone, and cisplatin) on relapsed or refractory aggressive non-Hodgkin's Lymphoma: a report of 24 cases]. [2015]

2. United States pubmed.ncbi.nlm.nih.gov

Gemcitabine, dexamethasone, and cisplatin in patients with recurrent or refractory aggressive histology B-cell non-Hodgkin lymphoma: a Phase II study by the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG). [2022]

3. United States pubmed.ncbi.nlm.nih.gov

cis-dichlorodiammineplatinum(II) with and without ICRF-159 in non-Hodgkin's lymphoma. [2013]

4. Turkey pubmed.ncbi.nlm.nih.gov

Gemcitabine, dexamethasone and cisplatin (GDP) is an effective and well-tolerated mobilization regimen for relapsed and refractory lymphoma: a single center experience [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Cisplatin plus gemcitabine versus a cisplatin-based triplet versus nonplatinum sequential doublets in advanced non-small-cell lung cancer: a Spanish Lung Cancer Group phase III randomized trial. [2022]

6. Japan pubmed.ncbi.nlm.nih.gov

[Phase I study of a new antineoplastic agent, cis-diamminedichloroplatinum (II)]. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

Toxic effects of cis-dichlorodiammineplatinum(II) in man. [2022]

8. Japan pubmed.ncbi.nlm.nih.gov

[Phase II study on cis-diamminedichloroplatinum (II) by a collaborative study]. [2013]

9. Germany pubmed.ncbi.nlm.nih.gov

Phase I clinical evaluation of [SP-4-3(R)]-[1,1-cyclobutanedicarboxylato(2-)](2-methyl-1,4- butanediamine-N,N1) platinum in patients with metastatic solid tumors. [2019]

10. France pubmed.ncbi.nlm.nih.gov

[Cis-diammino-dichloro-platinum therapy of cancers; phase II therapeutic trial]. [2013]

11. United States pubmed.ncbi.nlm.nih.gov

Phase II evaluation of cis-dichlorodiammineplatinum(II) in lymphomas: a Southwest Oncology Group Study. [2013]

12. Japan pubmed.ncbi.nlm.nih.gov

[Recent advances in ovarian cancer chemotherapy]. [2018]

13. Germany pubmed.ncbi.nlm.nih.gov

[Cis-diamminedichloroplatinum(II). A new antineoplastic agent derived from the group of heavy metal complexes (author's transl)]. [2019]

14. Switzerland pubmed.ncbi.nlm.nih.gov

Platinum complexes in cancer chemotherapy. [2013]