RUTKOWSKI

"This trial will be open and activated in 23 countries, including [the] US and [countries within the] EU, and more than 700 patients will be included. From my perspective, [this study is[ very attractive."

Piotr Rutkowski, MD, a professor of surgical oncology, head of the Department of Soft Tissue/Bone Sarcoma and Melanoma, and the plenipotentiary director of the Institute for Clinical Trials at the Maria Sklodowska-Curie National Research Institute of Oncology, discussed the design and objectives of the NivoReach study (NCT06587451), a phase 3 trial evaluating the proposed nivolumab (Opdivo) biosimilar JPB898 in combination with ipilimumab (Yervoy) vs reference nivolumab plus ipilimumab in patients with untreated, unresectable stage III or metastatic stage IV melanoma.

To conduct the study, investigators are enrolling approximately 720 patients across approximately 23 countries, including the United States (US) and nations within the European Union (EU). Patients must have an ECOG performance status of 0 or 1; those with active brain metastases, uveal melanoma, or other untreated or progressive malignancies will be excluded. Eligible patients will be randomly assigned 2:1 to receive either JPB898 or EU/US-authorized nivolumab, each combined with ipilimumab. Randomization is stratified by 

 V600 mutation status, PD-L1 expression, and metastasis stage.

In the 12-week induction phase, all patients will receive nivolumab at 3 mg/kg plus ipilimumab at 1 mg/kg every 3 weeks. Rutkowski highlighted the rationale for this dosing approach, referencing prior data from the phase 3b/4 CheckMate 511 trial (NCT02714218) that demonstrated a favorable toxicity profile and comparable efficacy with lower-dose ipilimumab. He emphasized the potential clinical appeal of such a regimen in routine practice, particularly if a biosimilar option like JPB898 is shown to perform comparably to the reference product.

During the maintenance phase, patients will receive fixed-dose JPB898 or reference nivolumab monotherapy at 480 mg every 4 weeks from week 16 to week 48. The coprimary pharmacokinetic end points include area under the serum concentration–time curve after the first and fourth induction doses. The primary efficacy end point is best overall response (complete or partial) assessed at 28 weeks, with additional secondary end points of safety, immunogenicity, and further efficacy outcomes up to 52 weeks.

Videos

Piotr Rutkowski, MD, discusses a trial evaluating the nivolumab biosimilar JPB898 plus ipilimumab in stage III or metastatic stage IV melanoma.

Dr Rutkowski on JPB898 With Ipilimumab in Stage III or Metastatic Stage IV Melanoma

Dr Rutkowski on the Safety Profile of Avelumab Plus Axitinib in GIST

Piotr Rutkowski, MD, professor, Surgical Oncology, Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland, discusses the safety findings and clinical implications from the phase 2 AXAGIST trial (NCT04258956), which evaluated avelumab (Bavencio) in combination with axitinib (Inlyta) in patients with unresectable or metastatic gastrointestinal stromal tumors (GIST) who progressed on standard therapies.

Rutkowski explains that no new safety signals were identified in the AXAGIST trial. The majority of patients experienced adverse events (AEs), but most were grade 1 or 2 and were manageable. Rutkowski notes that immune-related AEs, commonly associated with PD-L1 inhibitors like avelumab, were mainly related to thyroid dysfunction. These events were manageable with standard interventions.

Notably, the safety profile of the avelumab and axitinib combination was consistent with that observed in previous studies, such as the phase 3 JAVELIN Renal 101 trial (NCT02684006). In this trial, avelumab plus axitinib also demonstrated a significantly longer progression-free survival (PFS) with avelumab plus axitinib than with sunitinib in patients with previously untreated advanced renal cell carcinoma (RCC) regardless of PD-L1 expression.

The AXAGIST trial enrolled a heavily pretreated population of patients with GIST who progressed on standard therapies, including TKIs such as imatinib (Gleevec) and sunitinib (Sutent). Although not all TKIs have been fully explored in this setting, the combination of axitinib, with its antiangiogenic and immunomodulatory effects, and avelumab, a PD-L1 inhibitor, could serve as an effective approach for certain subgroups of patients with GIST, Rurkowski suggests.

Rutkowski states that the AXAGIST trial represents the largest study exploring the combination of immunotherapy and TKI in this patient population to date. Study findings demonstrate that the combination was well tolerated and may provide an effective therapeutic option for patients with GIST who have limited treatment choices. This study may pave the way for future investigations of immunotherapy combinations in this setting, particularly for those with specific molecular subtypes of GIST.

Piotr Rutkowski, MD, discusses the safety and clinical implications of avelumab in combination with axitinib in unresectable or metastatic GIST

Dr Rutkowski on Avelumab Plus Axitinib in Unresectable/Metastatic GIST

Piotr Rutkowski, MD, professor, Surgical Oncology, Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, discusses findings from the phase 2 AXAGIST trial (NCT04258956), a single arm study of avelumab (Bavencio) in combination with axitinib (Inlyta) in patients with unresectable/metastatic gastrointestinal stromal tumor (GIST) who had progressed on standard therapy.

For patients who have progressed following treatment with imatinib (Gleevec), therapeutic options are typically limited, and adding more than a traditional TKI is often desired, Rutkowski begins. Axitinib, known for its antiangiogenic properties, also exerts an immunomodulatory effect, according to Rutkowski. This drug acts on KIT and PDGFR α/β, with an additional effect on VEGFR, making it a suitable candidate for combination therapy with avelumab, an anti–PD-L1 drug, he explains.

The rationale for combining these agents stems from evidence that this combination has been safe and effective in other cancer types, such as renal cell carcinoma, Rutkowski explains. Patients eligible for AXAGIST must have experienced disease progression within 3 months prior to enrollment, have had an ECOG performance status of 2 or lower, and have received prior therapy with imatinib and sunitinib (Sutent), without prior treatment with axitinib or avelumab. In this trial, the maximum treatment duration was 2 years, and the primary end point was theprogression-free survival (PFS) rate at 3 months. The 3-month PFS rate in evaluable patients (n = 56) was 57.1%, and the median PFS was 4.6 months (95% CI, 2.9-6.4). Additionally, the disease control rate was 69.6%, a significant outcome for this heavily pretreated patient population, he reports.

Importantly, the median overall survival (OS) was 14.2 months (95% CI, 9.2-26.3), which is particularly notable in patients who have undergone multiple prior lines of treatment, Rutkowski expands. At 12 months, 59.3% of patients were still alive, indicating promising long-term benefits with the combination, he emphasizes. Overall, the combination of avelumab and axitinib appears to be a highly promising therapeutic option for the third- or fourth-line management of GIST, he says. These findings indicate that this combination could represent a valuable treatment strategy for patients who have exhausted other options, Rutkowski concludes.

Piotr Rutkowski, MD, discusses an investigation of avelumab in combination with axitinib in patients with unresectable/metastatic GIST after progression.

Piotr Rutkowski, MD

Articles

Dr Rutkowski on JPB898 With Ipilimumab in Stage III or Metastatic Stage IV Melanoma

Dr Rutkowski on the Safety Profile of Avelumab Plus Axitinib in GIST

Dr Rutkowski on Avelumab Plus Axitinib in Unresectable/Metastatic GIST