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Biotechnology company Peptilogics announced today that it has completed a $78 million financing round to support a phase 2/3 trial of its investigational treatment for prosthetic joint infections (PJIs).

The upcoming randomized controlled trial will enroll 240 patients beginning in December to determine whether zaloganan, an antibacterial and antibiofilm peptide developed by the Pittsburgh-based company, is superior to the current standard of care for PJIs in reducing clinical failure rates. The trial will also evaluate hospitalization duration, readmission rates, and the need for additional surgical procedures. Failure rates for current approaches range from 15% to 50%.

An estimated 45,000 PJI cases occur in the United States each year, and more are expected as the population ages and the number of knee and hip replacements rises. 

Drug targets biofilms

Zaloganan works by targeting and disrupting bacterial membranes and has demonstrated broad-spectrum activity against a wide range of pathogens. In a phase 1 trial in patients with PJIs, which are mediated by biofilms from the causative pathogens that grow on implanted hardware, 13 of 14 patients who received zaloganan irrigation during debridement, antibiotics, and implant retention procedures remained infection-free at 12 months.

“Biofilm is the common enemy and the reason why existing standard-of-care surgical interventions fail, even with systemic antibiotics,” Peptilogics CEO Nick Pachuda, DPM, said in the press release. “Zaloganan quickly penetrates the biofilm locally and kills the hiding bacteria.”

Among the investors in the Series B2 financing round is the AMR Action Fund, which was launched in 2020 to help companies developing promising treatments for antibiotic-resistant infections.   

“Periprosthetic joint infections are a striking example of how antimicrobial resistance is rapidly undermining modern medicine,” said AMR Action Fund CEO Henry Skinner, PhD. “The financial costs, diminished quality of life, and mortality associated with such infections are frankly unacceptable, and we are pleased to support the Peptilogics team as they advance zaloganan through the clinic and toward patients in need.”

In January the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) awarded Peptilogics $3.3 million to develop a slow-release version of zaloganan.

Introduction

Chimeric antigen receptor (CAR) T-cell therapy is a treatment option for patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) after first-line treatment and who are ineligible for autologous hematopoietic cell transplantation (autoHCT). However, access to CAR T-cell therapy remains a challenge. Additional treatment options are still needed, especially for those who are not candidates for CAR T-cell therapy. Epcoritamab (Epkinly; Genmab), a CD20 × CD3 bispecific antibody (BsAb), plus gemcitabine and oxaliplatin (Epcor-GemOx), has been evaluated in the phase 1b/2 EPCORE NHL-2 trial (NCT04663347), and glofitamab (Columvi; Genentech/Roche), a CD20 × CD3 BsAb, plus GemOx, has been evaluated in the phase 3 randomized STARGLO trial (NCT04408638). These 2 regimens provide off-the-shelf treatment options for a patient population that has historically faced low overall and complete response rates of 26% and 7%, respectively.^1-3 Herein, we focus on considerations for operationalizing Epcor-GemOx in practice for the oncology pharmacist. Areas of emphasis should include an understanding of optimizing patient selection based on comparative efficacy and safety outcomes with similar regimens, therapy sequencing for R/R DLBCL, and toxicity prevention and management with a thorough program of monitoring, prevention, and early treatment. These are particularly important in the setting of rapid clinical development of these BsAb agents—as clinical use is examined in a growing number of hematologic malignancies—an increasing variety of combination regimens, and earlier lines of therapy.^3-11

EPCORE NHL-2 Trial Overview

Study Design and Population

EPCORE NHL-2 is a global, open-label, phase 1b/2 trial investigating epcoritamab-based regimens for treatment of DLBCL and follicular lymphoma in various settings (such as treatment-naive, R/R, and maintenance).³ Arm 5 of the EPCORE NHL-2 trial evaluated Epcor-GemOx for treatment of adult patients (≥ 18 years) with histologically confirmed R/R DLBCL, notably including double- and triple-hit lymphoma with DLBCL morphology. Enrolled patients had to have at least 1 prior systemic therapy and not be candidates for autoHCT due to age, performance status, comorbidities, or previous failure of autoHCT.

Treatment Schedule and Administration

Epcor-GemOx was administered for four 28-day cycles, followed by epcoritamab monotherapy until disease progression or intolerance. Step-up dosing of epcoritamab occurred with cycle 1, and the full dose of epcoritamab was 48 mg. GemOx was administered on days 1 and 15 of cycles 1 to 4. The timing and administration order of medications aimed to maximize efficacy and safety.^3,12,13

Key Points

• Cycle length: 28 days
• Treatment duration: Epcoritamab was continued until disease progression or unacceptable toxicity.
• Agents by cycle and day of treatment:
  • Cycle 1
    • Day 1: Epcoritamab 0.16 mg subcutaneously (step-up dose 1) plus gemcitabine 1000 mg/m² intravenously (IV) and oxaliplatin 100 mg/m² IV (GemOx)
    • Day 8: Epcoritamab 0.8 mg subcutaneously (step-up dose 2)
    • Day 15: Epcoritamab 48 mg subcutaneously (first treatment dose) plus GemOx
      • Hospitalization for cytokine release syndrome (CRS) monitoring was required for the first treatment dose (C1D15) and for 24 hours after administration. Hospitalization for subsequent doses could be considered in the event of grade 2 or greater CRS events and/or need for repriming in the case of a dose delay. The epcoritamab package insert currently recommends that patients with DLBCL or high-grade B-cell lymphoma be hospitalized for 24 hours after administration of the C1D15 dose of 48 mg.
    • Day 22: Epcoritamab 48 mg subcutaneously
  • Cycles 2 and 3
    • Day 1: Epcoritamab 48 mg subcutaneously plus GemOx
    • Day 8: Epcoritamab 48 mg subcutaneously
    • Day 15: Epcoritamab 48 mg subcutaneously plus GemOx
    • Day 22: Epcoritamab 48 mg subcutaneously
  • Cycle 4
    • Day 1 and 15: Epcoritamab 48 mg subcutaneously plus GemOx
  • Cycles 5 to 9:
    • Day 1 and 15: Epcoritamab 48 mg subcutaneously
  • Cycles 10
    • Day 1: Epcoritamab 48 mg subcutaneously
• Administration order: GemOx was administered prior to epcoritamab (and epcoritamab-associated premedications)

Supportive Care

Similar to other BsAb-based regimens, Epcor-GemOx requires premedications for initial doses to reduce the risk of CRS; these include corticosteroids, antihistamines, and antipyretics. Other supportive care that pharmacists should consider includes granulocyte colony-stimulating factor (G-CSF) prophylaxis and infection prophylaxis.^3,12-16

Key Points

• Premedications for epcoritamab were required for cycle 1 and could have been omitted for subsequent cycles if grade 2 or 3 CRS did not occur with the prior dose of epcoritamab.
  • Glucocorticoid (eg, dexamethasone 15 mg orally or IV or equivalent)
    • Dexamethasone was preferred over prednisolone, as it is a superior corticosteroid for prevention of CRS and is associated with lower rates of CRS.^16,17 In practice, a dose of dexamethasone 16 mg is commonly utilized given the availability of the 4-mg tablet strength.
  • Antihistamine (eg, diphenhydramine 50 mg orally or IV)
  • Antipyretic (eg, acetaminophen 650 or 1000 mg orally)
• Emetogenicity on days of combination therapy necessitates 2 or more antiemetic premedications.
  • Moderate risk: oxaliplatin
  • Low risk: epcoritamab, gemcitabine
• Tumor lysis syndrome (TLS) prophylaxis was determined by institutional standards. TLS risk is dependent on factors like baseline tumor burden and renal impairment. In practice, common prophylactic measures include hydration (usually 2-3 L/day; either orally or IV depending on TLS risk) and antihyperuricemic agent (eg, allopurinol) for patients with high risk of TLS.
• G-CSF was mandated in arm 5 with recurrent grade 3 or higher neutropenia; otherwise, G-CSF was optional. Primary prophylaxis could be considered with GemOx cycles, which are known to be myelosuppressive. Vaccines were recommended to be administered at least 4 weeks prior to the start of treatment.

Anti-infective prophylaxis for viral, fungal, bacterial, or Pneumocystis Jirovecii (PJP) infections was allowed and dependent on patient risk factors; however, PJP prophylaxis is also required per the epcoritamab labeling for standard-of-care practice. For arm 5, the protocol required antiviral prophylaxis for patients with a history of recurrent herpes virus infections, prior herpes infection during a prior line of therapy, or neutropenia and/or a CD4+ cell count less than 200 cells/µL. PJP prophylaxis was mandated if 4 or more consecutive days of corticosteroids were administered (eg, during cycle 1) and for those at an increased risk (eg, patients with a low CD4+ cell count < 350 cells/µL). Prophylaxis for hepatitis B reactivation was mandated if a baseline positive hepatitis B virus core antibody was reported.

Dose Adjustments and Treatment Interruptions

In addition to often institution-directed supportive care measures, the EPCORE NHL-2 protocol provided direction on dose reductions and treatment holds. Assessment of complete blood count thresholds and TLS-related laboratory values will impact need for dose modification.^3,12,13

Key Points

1. Platelet threshold for GemOx: ≥ 75,000/μL. If bone marrow infiltration or splenomegaly, ≥ 50,000/μL.
2. Absolute neutrophil count threshold: ≥ 1,000/μL
3. Hemoglobin threshold: > 8 g/dL
4. Oxaliplatin dose modification: Reduce to 75 mg/m² (25%) for neurotoxicity or hematologic toxicity. Consider longer infusion up to 6 hours for pharyngolaryngeal dysesthesia.

Prohibited and Restricted Medications

The EPCORE NHL-2 protocol prohibited certain medications during and after treatment, with the aim of limiting undue toxicities. Oncology pharmacists should screen for and advise on prevention of these interactions.³

Key Points

Prohibited therapies:

• Live vaccines from 28 days pretreatment to 3 months posttreatment
• Immunostimulatory agents
• Investigational agents

Use with caution:

Herbal preparations

Efficacy and Safety Outcomes

The primary end point was overall response rate (ORR), which included complete response (CR) and partial response. Secondary end points included complete response rate (CRR), time to response, progression-free survival (PFS), and duration of response. The data cutoff date was December 15, 2023, and median follow-up for efficacy was 13.2 months.

1. In the overall population, ORR by independent review committee assessment was 85% (CRR, 61%). First response for the overall population was seen at a median of 1.5 months (range, 0.9-3), with about an additional month of therapy for median time to CR (2.6 months [range, 1.3-22.1]).
2. The median PFS for the overall population and for patients with a CR was 11.2 months (95% CI, 8.0-14.7) and 26.7 months (95% CI, 11.7-not reached [NR]), respectively, while the median overall survival (OS) was 21.6 months (95% CI, 11.6-NR) for the overall population and NR (95% CI, NR-NR) for patients with CR.
3. 12-month PFS and OS rates were 44% (95% CI, 31.7%-55.5%) and 56.6% (95% CI, 45.5%-66.3%), respectively.
4. Notably, patients who were less heavily pretreated (1 prior line of therapy) demonstrated higher CR rates and higher 12-month PFS and OS rates compared with the cohort with more than2 lines of therapy. CRR was relatively lower for subgroups including those who received prior CAR T-cell therapy and prior autoHCT. Time to response was similar.
5. Understanding the utility of measuring minimal residual disease negativity for R/R DBLCL is ongoing; exploratory findings were reported or are planned in EPCORE NHL-2 and other trials.^3,9

In addition to the efficacy outcomes above, safety was a secondary objective assessed in 103 patients.

1. CRS: Fifty-two percent (n = 54) of patients experienced CRS; most events were grades 1 to 2, with only 1 patient developing grade 3 CRS. Thirty-nine percent of patients experienced CRS with the first treatment dose. All events resolved, and none led to epcoritamab discontinuation. Twenty-three percent of patients (n = 24) with CRS events were treated with tocilizumab, while 16.5% (n = 17) were treated with corticosteroids.
2. ICANS: Three percent (n = 3) of patients experienced immune effector cell–associated neurotoxicity syndrome (ICANS); 1 event was grade 3 or higher.
3. Infections: All-grade events occurred in 72% of assessed patients (29% grade > 3). Related grade 5 events: COVID-19 infection (n = 5), lung infection and COVID-19 (n = 2), enterocolitis (n = 1), and Escherichia coli sepsis (n = 1).
4. No clinical TLS events were reported.

Treatment Monitoring Requirements

Successful implementation of Epcor-GemOx requires close attention to clinical and laboratory assessments. A growing body of consensus guidance, systemic reviews, and retrospective data highlights the importance of early recognition and intervention for infections, CRS, and ICANS associated with BsAb-related regimens.^15-18 Robust institutional protocols for toxicity prevention and management should be utilized to achieve this objective.

Highlights of Trial Differences

The STARGLO (Glofit-GemOx) and EPCORE NHL-2 (arm 5) (Epcor-GemOx) trials support regimens that are both used to treat patients with R/R DLBCL who are transplant-ineligible.^1,3,19 Factors to consider for treatment selection beyond comparative efficacy and safety outcomes include administration logistics, patient preference, insurance coverage, and enrolled patient characteristics. Some topline differences between the 2 regimens are highlighted in Table 1.^20,21

Conclusion

The EPCORE NHL-2 trial demonstrates continued progress in interrogating and improving historically poor outcomes for patients with R/R DLBCL who are transplant-ineligible. With Epcor-GemOx, patients have the option for a regimen with a subcutaneously administered BsAb and that is off the shelf, with promising efficacy end points and tolerable safety outcomes. Oncology pharmacists are well positioned to apply their expertise. Opportunities include, but are not limited to, optimizing patient selection for this regimen, educating on sequencing of therapies, informing builds of evidence-based therapeutic and supportive care plans in the electronic health record, ensuring smooth transitions of care, and limiting safety events by ensuring appropriate monitoring, prevention, and management of toxicities like infections, CRS, and ICANS. This background will ensure that pharmacy teams will continue to lead the rollout and delivery of additional CD20 × CD3 BsAb-based regimens on the horizon with ongoing trials evaluating epcoritamab and glofitamab in frontline management of DLBCL, particularly epcoritamab-R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone; EPCORE DLBCL-2 trial; NCT05578976)²² and glofitamab-Pola-R-CHP (polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone; SKYGLO trial; NCT06047080).²³

REFERENCES

1. Abramson JS, Ku M, Hertzberg M, et al. Glofitamab plus gemcitabine and oxaliplatin (GemOx) versus rituximab-GemOx for relapsed or refractory diffuse large B-cell lymphoma (STARGLO): a global phase 3, randomised, open-label trial. Lancet. 2024;404(10466):1940-1954. doi:10.1016/S0140-6736(24)01774-4

2. Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130(16):1800-1808. doi:10.1182/blood-2017-03-769620

3. Brody JD, Jørgensen J, Belada D, et al. Epcoritamab plus GemOx in transplant-ineligible relapsed/refractory DLBCL: results from the EPCORE NHL-2 trial. Blood. 2025;145(15):1621-1631. doi:10.1182/blood.2024026830

4. Safety and efficacy trial of epcoritamab combinations in subjects with B-cell non-Hodgkin lymphoma (B-NHL) (EPCORE™ NHL-2). ClinicalTrials.gov. Updated September 3, 2025. Accessed September 9, 2025. https://clinicaltrials.gov/study/NCT04663347

5. A phase III study evaluating glofitamab in combination with gemcitabine + oxaliplatin vs rituximab in combination with gemcitabine + oxaliplatin in participants with relapsed/​refractory diffuse large B-cell lymphoma. ClinicalTrials.gov. Updated July 14, 2025. Accessed September 9, 2025. https://clinicaltrials.gov/study/NCT04408638 

6. Linton KM, Vitolo U, Jurczak W, et al. Epcoritamab monotherapy in patients with relapsed or refractory follicular lymphoma (EPCORE NHL-1): a phase 2 cohort of a single-arm, multicentre study. Lancet Haematol. 2024;11(8):e593-e605. doi:10.1016/S2352-3026(24)00166-2

7. Phillips TJ, Carlo-Stella C, Morschhauser F, et al. Glofitamab in relapsed/refractory mantle cell lymphoma: results from a phase I/II study. J Clin Oncol. 2024;43(4):318-328. doi:10.1200/JCO.23.02470

8. Minson A, Verner E, Giri P, et al. A randomized phase 2, investigator-led trial of glofitamab-R-CHOP or glofitamab-polatuzumab vedotin-R-CHP (COALITION) in younger patients with high burden, high-risk large B-cell lymphoma demonstrates safety, uncompromised chemotherapy intensity, a high rate of durable remissions, and unique FDG-PET response characteristics. Blood. 2024;144(suppl 1):582. doi:10.1182/blood-2024-204930

9. Minson A, Verner E, Giri P, et al. Glofitamab combined with Pola-R-CHP or R-CHOP as first therapy in younger patients with high-risk large B-cell lymphoma: results from the COALITION study. J Clin Oncol. 2025;43(23):2595-2605. doi:10.1200/JCO-25-00481

10. Advani RH, Dickinson MJ, Fox CP, et al. SKYGLO: a global phase III randomized study evaluating glofitamab plus polatuzumab vedotin + rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) versus Pola-R-CHP in previously untreated patients with large B-cell lymphoma (LBCL). Blood. 2024;144(suppl 1):1718.1. doi:10.1182/blood-2024-194000

11. Sehn LH, Chamuleau M, Lenz G, et al. Phase 3 trial of subcutaneous epcoritamab + R-CHOP versus R-CHOP in patients (pts) with newly diagnosed diffuse large B-cell lymphoma (DLBCL): EPCORE DLBCL-2. J Clin Oncol. 2023;41(suppl 16). doi:10.1200/JCO.2023.41.16_suppl.TPS759

12. Epkinly. Prescribing information. Genmab US Inc; 2024. Accessed September 15, 2025. https://www.genmab-pi.com/prescribing-information/epkinly-pi.pdf

13. Gazyva. Prescribing information. Genentech Inc; 2022. Accessed September 15, 2025. https://www.gene.com/download/pdf/gazyva_prescribing.pdf

14. Vose JM, Feldman T, Chamuleau MED, et al. Mitigating the risk of cytokine release syndrome (CRS): preliminary results from a DLBCL Cohort of Epcore NHL-1. Blood. 2023;142(suppl 1):1729. doi:10.1182/blood-2023-180333

15. Crombie JL, Graff T, Falchi L, et al. Consensus recommendations on the management of toxicity associated with CD3×CD20 bispecific antibody therapy. Blood. 2024;143(16):1565-1575. doi:10.1182/blood.2023022432

16. Bastos-Oreiro M, Iacoboni G, Navarro Garces V, et al. Real-world management patterns of acute toxicity following bispecific antibody therapy for patients with B-cell lymphoma – the Geltamo (Spanish Lymphoma Group) Experience. Blood. 2024;144(suppl 1):3109-3109.

17. Yang X, Ahmed I, Nachar V, et al. Risk factors for cytokine release syndrome in patients receiving bispecific antibodies for B-Cell lymphoma: a single-center, retrospective cohort study. Blood. 2024;144(suppl 1):4477.

18. Bangolo A, Amoozgar B, Mansour C, et al. Comprehensive review of early and late toxicities in CAR T-cell therapy and bispecific antibody treatments for hematologic malignancies. Cancers (Basel). 2025;17(2).

19. Gurion R, Mazza IA, Thieblemont C, et al. Fixed-duration epcoritamab plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL): updated results from arm 1 of the Epcore NHL-5 Trial. Blood. 2024;144(suppl 1):3110.

20. Vose JM, Feldman T, Chamuleau MED, et al. Mitigating the risk of cytokine release syndrome (CRS): preliminary results from a DLBCL cohort of Epcore NHL-1. Blood. 2023;142(suppl 1):1729. doi:10.1182/blood-2023-180333

21. Abramson JS, Ku M, Hertzberg M, et al. Glofitamab plus gemcitabine and oxaliplatin (Glofit-GemOx) in patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): 2-year (yr) follow-up of STARGLO. J Clin Oncol. 2025;43(suppl 16):7015. doi:10.1200/JCO.2025.43.16_suppl.7015

22. A study to evaluate change in disease activity of subcutaneous (SC) epcoritamab combined with intravenous and oral rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (R-CHOP) or R-CHOP in adult participants with newly diagnosed diffuse large B-cell lymphoma (DLBCL) (EPCORE DLBCL-2). ClinicalTrials.gov. Updated January 23, 2025. Accessed September 9, 2025. https://clinicaltrials.gov/study/NCT05578976

23. An open-label study comparing glofitamab and polatuzumab vedotin + rituximab, cyclophosphamide, doxorubicin, and prednisone versus Pola-R-CHP in previously untreated patients with large B-cell lymphoma. ClinicalTrials.gov. Updated September 3, 2025. Accessed September 9, 2025. https://clinicaltrials.gov/study/NCT06047080

“Cleaner flight is possible, but it requires changing how we think about both risk and return,” Victor said. “We need new institutions, incentives, and partnerships that reward innovation, not just incrementalism.”

The commentary, written by a multinational team of scholars, also highlights a broader lesson for climate policy: global decarbonization goals such as “net zero by 2050” sound bold and ambitious.  But when it becomes clear that they can’t be met these goals make it harder to focus on the practical steps needed today to drive change in real-world markets.

Ultimately, the paper argues for action that begins now. By developing better tools to evaluate climate-friendly investments and by rewarding companies willing to take calculated risks on breakthrough technologies, governments, investors and industry leaders can accelerate real progress toward decarbonization. 

The paper was co-authored by Thomas Conlon of University College Dublin, Philipp Goedeking of Johannes Gutenberg University of Mainz (Germany) and Andreas W. Schäfer of University College London. 

Read the full article, “Mobilizing Capital and Technology for a Clean Aviation Industry,” in Science.  

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