Jad Chahoud, MD, MPH, MHA, is an associate member in the Department of Genitourinary Oncology and medical director of IPOP at Moffitt Cancer Center.

Jad Chahoud, MD, MPH

“We didn’t see…grade 3 CRS [effects], which was great. We [also] didn’t see any GVHD, which is great for patients receiving an allogeneic CAR T-cell therapy.”

Jad Chahoud, MD, MPH, an associate member of the Department of Genitourinary Oncology and medical director of IPOP at Moffitt Cancer Center, discussed safety data with the off-the-shelf, HLA-unmatched, CD70-directed CAR T-cell therapy ALLO-316 for the treatment of patients with advanced clear cell renal carcinoma (ccRCC).

, investigators presented data from the phase 1 TRAVERSE study (NCT04696731), which evaluated the safety profile of ALLO-316 in patients with CD70-positive ccRCC who had received prior PD-1 axis– and VEGF-targeted therapies.

Findings from TRAVERSE revealed that no patients experienced grade 3 or higher cytokine release syndrome (CRS), Chahoud said. All CRS events were limited to grade 1 or 2 in severity. Notably, no cases of graft-vs-host disease (GVHD) were observed, he added, underscoring the tolerability of allogeneic CAR T-cell therapy in this population.

A more clinically significant toxicity was immune effector cell–associated hemophagocytic lymphohistiocytosis (IEC-HS), Chahoud explained. Two patients experienced grade 3 or higher IEC-HS–like events, though none were fatal, he said. Importantly, a structured management approach was developed to address this complication, which allowed most patients to continue treatment successfully, according to Chahoud.

Additional treatment-emergent adverse effects included fatigue, loss of appetite, and nausea, which were generally manageable, he noted. Grade 3 or higher hematologic included neutropenia and thrombocytopenia. Interstitial lung disease (ILD) occurred in a small proportion of patients, with approximately 2 experiencing grade 3 ILD that required treatment discontinuation, he added.

Chahoud emphasized that no treatment-related deaths occurred in the study, and no new safety signals were identified. He concluded that ALLO-316 was associated with a manageable safety profile characterized by low-grade CRS, the absence of GVHD, and isolated cases of IEC-HS, which can be effectively addressed through proactive management strategies.

Videos

 Jad Chahoud, MD, MPH, discusses the safety profile of ALLO-316 for the treatment of patients with advanced clear cell renal carcinoma.

Dr Chahoud on the Safety of ALLO-316 in Advanced ccRCC

Dr Chahoud on ALLO-316 in Advanced Clear Cell Renal Cell Carcinoma

“These patients [can receive ALLO-316] and go on without any therapy, they just need to be monitored with repeat scans. [The long-term responders] are a sign that these CAR [T-cell therapies] do a good, long-lasting job.”

Jad Chahoud, MD, MPH, an associate member of the Department of Genitourinary Oncology and medical director of IPOP at Moffitt Cancer Center, discussed efficacy data with the off-the-shelf, HLA-unmatched, CD70 CAR T-cell therapy ALLO-316 for the treatment of patients with advanced clear cell renal carcinoma (ccRCC).

, investigators presented data from the phase 1 TRAVERSE study (NCT04696731), which examined ALLO-316 in patients with CD70-positive ccRCC who experienced disease progression after PD-1 axis and VEGF-targeted therapies. The patient population was heavily pretreated, with a median of 4 (range, 1-11) prior lines of therapy.

Findings from TRAVERSE revealed that patients with a CD70 tumor proportion score (TPS) of at least 50% who received ALLO-316 in phase 1a or 1b experienced a confirmed overall response rate (ORR) of 26% (n = 8/31), Chahoud said. Additionally, the confirmed ORR among patients treated in phase 1b with a CD70 TPS of at least 50% (n = 16) was 31%, he added. Forty-four percent of patients with a CD70 TPS of at least 50% treated in phase 1b experienced a reduction of over 30% in the diameter of baseline targeted lesions, he noted.

Regarding response duration, 1 patient out of 5 confirmed responders has remained in response for more than 1 year as of the May 2, 2025, data cutoff, Chahoud said. There are 2 additional patients who have been in response for 7 and 9 months, respectively, he added. Chahoud noted that patients can receive ALLO-316 as a one-time infusion and can continue without treatment while being monitored with repeat scans.

Jad Chahoud, MD, MPH, discusses the CAR T-cell therapy ALLO-316 in advanced clear cell renal carcinoma (ccRCC).

Jad Chahoud, MD, MPH, discusses the background and rationale for evaluating zanzalintinib plus nivolumab with or without relatlimab in ccRCC.

Dr Chahoud on the Rationale for Evaluating Zanzalintinib Plus Nivolumab With/Without Relatlimab in ccRCC

“STELLAR-002 is a phase [1], multiple-arm, dose escalation, dose expansion trial, trying to look at a new VEGF TKI, zanzalintinib, that has a shorter half-life, which usually helps a lot with the management of a lot of multi-TKI toxicities, in combination with nivolumab alone or in combination with relatlimab.”

Jad Chahoud, MD, MPH, an associate member in the Department of Genitourinary Oncology and medical director of IPOP at Moffitt Cancer Center, detailed the rationale for evaluating zanzalintinib (XL092) plus nivolumab (Opdivo) with or without relatlimab-rmbw (Opdualag) for the treatment of patients with previously untreated clear cell renal cell carcinoma (ccRCC).

The phase 1b STELLAR-002 trial (NCT05176483) evaluates the novel VEGF TKI, zanzalintinib, which has a shorter half-life and usually contributes toward the management of multi-TKI toxicities, Chahoud began. The regimen used in the study also includes nivolumab with or without relatlimab, he explained. Of note, many of the FDA-approved frontline therapies for ccRCC are a combination of immunotherapy plus VEGF TKIs or immunotherapy plus immunotherapy regimens, with no triplet regimens currently approved, he added.

The study includes patients at least 18 years of age with unresectable advanced or metastatic ccRCC who had not previously received systemic anticancer therapy for RCC. However, those who had previously received non-VEGF(R)–targeted adjuvant or neoadjuvant therapy are allowed on the study if disease recurrence occurred 6 months following the last dose. Additionally, patients from all IMDC risk groups are eligible. In the expansion cohort, patients are treated with either zanzalintinib at 100 mg daily plus nivolumab at 480 mg (n = 40) or zanzalintinib at the same dose level plus nivolumab at 480 mg and relatlimab at 480 mg every 4 weeks (n = 40).

The dual primary end points are safety and objective response rate per RECIST 1.1 criteria. The secondary end point is progression-free survival per RECIST 1.1 criteria.

At a median follow-up of 20.1 months (range, 17.7-26.7) in the doublet arm and 15.9 months (range, 11.3-17.3) in the triplet arm, reasons for discontinuation of all study treatment included radiographic progression (doublet, 33%; triplet, 23%), any treatment-emergent adverse effect (TEAE; 25%; 35%), AEs related to study treatment (8%; 20%), withdrawal of consent other than AE (3%; 3%), and physician decision (3%; 0%).

Dr Chahoud on Early Efficacy With Zanzalintinib Plus Nivolumab With/Without Relatlimab in ccRCC

"[We saw a] very deep, active response [with this regimen] that appears to be durable. Three-quarters of patients are still on study and in response, as of the data cutoff."

Jad Chahoud, MD, MPH, MHA, an associate member in the Department of Genitourinary Oncology and medical director of IPOP at Moffitt Cancer Center, discussed results from the dose-expansion cohort of the phase 1b STELLAR-002 study (NCT05176483), which evaluated zanzalintinib plus nivolumab (Opdivo) with or without relatlimab-rmbw (Opdualag) in patients with previously untreated clear cell renal cell carcinoma (ccRCC).

In the dose-escalation cohort, the investigators identified the recommended dose and assessed safety, Chahoud stated. Initial signals of activity were observed not only in patients with ccRCC but also in those with prostate and colorectal cancers, which informed the decision to advance into the dose-expansion cohorts, Chahoud explained.

, findings from the ccRCC cohort were presented. The zanzalintinib plus nivolumab doublet demonstrated an overall response rate (ORR) of 63% (95% CI, 46%-77%), comprised of an 8% complete response rate (CR) and 55% partial response rate (PR), Chahoud reported. One additional patient achieved a confirmed PR after the data cutoff, increasing the ORR to approximately 65%, Chahoud added.

In contrast, the triplet arm comprised of zanzalintinib plus nivolumab plus relatlimab showed a lower ORR of 40% (95% CI, 25%-57%), including 3% CR and 38% PR rates, Chahoud stated. At the time of the data cutoff, 5 patients in this arm had unconfirmed partial responses that may convert upon longer follow-up, he noted.

The doublet cohort had a longer median follow-up of 20.1 months compared with 15.9 months for the triplet cohort, Chahoud reported. The disease control rate was 90% (95% CI, 76%-97%) in both arms. The median time to treatment response was 2.1 months (range, 1.7-11.0) in the doublet arm and 3.6 months (range, 1.7-12.8) in the triplet cohort, Chahoud emphasized.

Regarding duration of response, the 12-month duration of response rate was 73.4% (95% CI, 50.0%-87.1%) with the doublet and 74.1% (95% CI, 39.1%-90.9%) with the triplet, Chahoud stated.

Jad Chahoud, MD, MPH, MHA, shares early-phase data with zanzalintinib plus nivolumab with or without relatlimab-rmbw in previously untreated ccRCC.

Jad Chahoud, MD, MPH, MHA

Articles

Dr Chahoud on the Safety of ALLO-316 in Advanced ccRCC

Dr Chahoud on ALLO-316 in Advanced Clear Cell Renal Cell Carcinoma

Dr Chahoud on the Rationale for Evaluating Zanzalintinib Plus Nivolumab With/Without Relatlimab in ccRCC

Dr Chahoud on Early Efficacy With Zanzalintinib Plus Nivolumab With/Without Relatlimab in ccRCC