®, has been with MJH Life Sciences since June 2023. She graduated with a B.A. in Communication Studies from Rowan University. Outside of work, Ashley enjoys spending time with family and friends, reading new novels by Asian American authors, and working on the manuscript of her New Adult novel.

Ashley Chan

The dual-targeting CAR T-cell therapy KITE-363 showed positive response rates and manageable side effects in relapsed or refractory B-cell lymphoma.

Among patients with relapsed/refractory B-cell lymphoma, the anti-CD19/CD20 CAR T-cell therapy KITE-363 showcased high response rates with a manageable safety profile, according to results from a first-in-human phase 1 study presented during the 

Safety data indicated that no dose-limiting toxicities were reported in phase 1a. Grade 3 (severe) or higher side effects were experienced by 2 patients who received the agent at dose level 1 (DL1; 3 patients), which was 0.5 x 10⁶ CAR T cells/kg. Grade 3 or higher side effects were reported in six patients who received dose level 2 (DL2; 8 patients), which was 1 x 10⁶ CAR T cells/kg. In those who received dose level 3 (DL3; 26 patients), which was 2 x 10⁶ CAR T cells/kg, the most common grade 3 or higher side effects included decreased white blood cell count (11 patients), neutropenia (8 patients) and decreased neutrophil count (11 patients).

Moreover, one grade 3 case of cytokine release syndrome (CRS) was reported in a patient with nodular lymphocyte-predominant Hodgkin lymphoma; the duration of the event was one day. Three grade 3 immune effector cell–associated neurotoxicity syndrome (ICANS) events were observed: one in the DL2 group, which had a duration of four days, and two in the DL3 group, which had durations of one and two days, respectively. Notably, no grade 3 or higher CRS or ICANS events were observed in those with primary refractory large B-cell lymphoma who received the CAR T-cell therapy at DL3 (15 patients).

In patients without prior exposure to CAR T-cell therapy who received KITE-363 at DL3 (23 patients), the objective response rate was 87%, and this was comprised of a complete response rate of 78% and a partial response rate of 9%. Four percent of patients had stable disease and 9% had progressive disease. Within this group, those with large B-cell lymphoma who had previously received at least two lines of therapy (seven patients) experienced an objective response rate and complete response rate of 100% each. Those with primary refractory large B-cell lymphoma (15 patients) experienced an objective response rate of 80% and a complete response rate of 67%. Of the 3 patients who had prior CAR T exposure and received DL3, one achieved a complete response.

Among those who received KITE-363 at DL1 and DL2 (11 patients), the objective response rate was 64%, with a complete response rate of 36% and a partial response rate of 27%. Nine percent experienced stable disease and 27% had progressive disease.

“These results support KITE-363 as a promising therapeutic approach for patients with relapsed/refractory B-cell lymphoma including those with highly refractory large B-cell lymphoma,” Saurabh Dahiya, MD, FACP, an associate professor of medicine at Stanford University School of Medicine in Stanford, California, said in a presentation of the data.

Keeping Up With KITE-363 and Its Evaluation in R/R B-Cell Lymphoma
The bicistronic, lentiviral-encoded autologous CAR T-cell therapy, KITE-363, is dual targeted. The anti-CD19 and anti-CD20 CAR possess a CD28 costimulatory domain and a 4-1BB costimulatory domain, respectively. “Dual targeting has the potential to address tumor heterogeneity and improve the durability of responses by preventing CD19-negative relapses,” Dahiya noted.

The open-label, multicenter, phase 1 study utilized a 3 plus 3 study design. It was comprised of a phase 1a dose-escalation portion and a phase 1b dose-expansion portion. For phase 1a, patients had histologically confirmed relapsed/refractory B-cell lymphoma by World Health Organization criteria following more than two lines of therapy or second-line primary refractory disease. Phase 1b only enrolled patients with relapsed/refractory large B-cell lymphoma, which included those with second-line primary refractory disease. All patients were at least 18 years of age and had an ECOG performance status of 0 or 1.

They were excluded if they had Richter transformation, central nervous system involvement of lymphoma, active infection, or a central nervous system disorder of clinical significance. Those with clinically significant autoimmune or cardiac disease were also excluded.

The primary end points for phase 1a and phase 1b were incidence of dose-limiting toxicities and objective response rate, respectively. Secondary end points included complete response rate, duration of response, progression-free survival, time to next treatment, overall survival, safety, and levels of CAR T cells and cytokines in the blood.

After screening, patients were enrolled and underwent leukapheresis. This was followed by optional bridging therapy, which was comprised of corticosteroids with or without local radiation therapy per investigator discretion. From day –five to –three, patients received lymphodepleting chemotherapy comprised of cyclophosphamide at 300 milligrams per square meter (mg/m²) daily and fludarabine at 30 mg/m² daily for three days. On day 0, patients were infused with KITE-363 at one of the three dose levels. For DL3, the median time from leukapheresis to infusion with the CAR T-cell therapy was 27 days. The first post-infusion response assessment was conducted on day 28.

A total of 41 patients were enrolled and underwent leukapheresis. Three of these patients were not treated, and the remaining 38 went on to receive lymphodepleting chemotherapy. Because one patient did not meet protocol-required eligibility to receive KITE-363, a total of 37 patients received the CAR T-cell therapy.

At the data cutoff date of March 18, 2025, the median follow-up in those who received treatment (37 patients) was 12.4 months. The median follow-up for those in the DL3 group was 11.1 months.

The median age for all treated patients was 62 years, with 46% aged 65 years or older and 11% aged 75 years or older. In the DL3 group, the median age was 60.5 years, with 42% aged 65 years or older and 12% aged 75 years or older. More than half of patients were male (65%), most were White (78%), most were not Hispanic or Latino (86%) and had an ECOG performance status of 1 (60%). Moreover, 73% of all treated patients had stage III or 4 disease at study entry, as did 65% of those in the DL3 group.

In all treated patients, the most common histologic subtype was large B-cell lymphoma (92%), followed by indolent non-Hodgkin lymphoma (5%) and nodular lymphocyte-predominant Hodgkin lymphoma (3%). In the DL3 group, the most common histologic subtype was also large B-cell lymphoma (96%), followed by nodular lymphocyte-predominant Hodgkin lymphoma (4%). Nineteen percent of all treated patients and 15% of those in the DL3 group had bulky disease, which was defined as at least 7.5 centimeters. Dahiya noted that patients had tumors that were positive for CD19 and/or CD20, with most patients (78%) having tumors that were positive for both. Thirteen percent of patients had tumors that were positive for 1 antigen.

In all treated patients, 46% were primary refractory and 54% had received two or more prior regimens. Nineteen percent received prior CD19-targeted CAR T-cell therapy, 14% previously underwent autologous stem cell transplant and 57% had received bridging therapy. In the DL3 group, 58% were primary refractory and 42% had received at least two prior lines of treatment. In the 15 patients who were primary refractory, four experienced partial responses as best response to frontline treatment and 11 experienced progressive disease. Prior CD19-targeted CAR T-cell therapy and prior autologous stem cell transplant were received by 12% and 15% of patients, respectively. Fifty-eight percent of patients in this group received bridging therapy.

The median duration of complete response, defined as duration of response of all patients who achieved a complete response as best response, was not reached. The duration of complete response rate at 6 months was 71.4%. “Data beyond 6 months is heavily impacted by censoring,” Dahiya noted. “Longer follow-up is needed.” Nine of the 37 patients who received treatment died; 8 died due to progressive disease.

Among those who received the CAR T-cell therapy at DL3, all patients experienced any-grade side effects. Eighty-one percent of these effects were grade 3 or higher. Any-grade and grade 3 or higher serious side effects were reported in 54% and 38% of patients, respectively. Any-grade cardiac disorders were experienced by 35% of patients; 4% were grade 3 or higher. Any-grade infections occurred in 42% of patients; 15% were grade 3 or higher. Hematologic side effects included neutropenia (any grade, 38%; grade 3 or higher, 31%), thrombocytopenia (8%; 4%) and anemia (31%; 15%). Hypogammaglobulinemia occurred in 15% of patients.

In those who received KITE-363 at DL1 or DL2, grade 1 or 2 CRS occurred in 64% of patients and grade 3 ICANS occurred in 9%. The median time to onset of CRS was six days and the median duration was three days. The median time to onset of ICANS was also 6sixdays and the median duration was six days. CRS was managed with Actemra in 45% of patients and corticosteroids in 27%. ICANS was managed with corticosteroids in 9% and Kineret in 9%.

In those who received the agent at DL3, grade 1 (mild) or 2 (moderate) CRS occurred in 88% and grade 3 CRS occurred in 4%. The median time to onset was 3.5 days and the median duration was five days. Most events were managed with Actemra (88%), followed by corticosteroids (65%) and Kineret (4%). Grade 1 or 2 ICANS was experienced by 38%; this effect was grade 3 for 8%. The median time to onset was six days and the median duration was 4.5 days. These effects were largely managed with corticosteroids (38%) followed by Kineret (15%).

Additional Revelations and Take-Home Message

“KITE-363 cell expansion was dose dependent, with markedly robust expansion observed in DL3, appearing greater than 3- to 5-fold higher than with Yescarta,” Dahiya said. Post-infusion peak levels of serum analytes were also linked with KITE-363 pharmacokinetics and reduced toxicity.

Due to these early results, the robust CAR T-cell expansion and the acceptable toxicity profile, the agent is also under development for patients with autoimmune disease, Dahiya concluded.

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Articles

KITE-363, an anti-CD19/CD20 CAR T-cell therapy, demonstrated high response rates and a manageable safety profile in relapsed/refractory B-cell lymphoma patients during a phase 1 study. The study revealed no dose-limiting toxicities, with varying side effects across different dose levels. The therapy showed promising efficacy, particularly at dose level 3, with high objective and complete response rates. The dual-targeting approach of KITE-363 aims to address tumor heterogeneity and improve response durability. The study's findings support further development of KITE-363 for relapsed/refractory B-cell lymphoma and autoimmune diseases.

KITE-363 Shows High Response in B-Cell Lymphoma With Manageable Safety

Camizestrant and continued therapy with CDK4/6 inhibition benefits patients who present with ESR1-mutated, ER+, HER2– advanced breast cancer: © stock.adobe.com.

Among patients with patients with ESR1-mutated, estrogen receptor (ER)–positive, HER2-negative advanced breast cancer, camizestrant plus continued therapy with CDK4/6 inhibition significantly improved progression-free survival outcomes compared with continued therapy with an aromatase inhibitor (AI) and CDK4/6 inhibitor when given prior to disease progression on frontline therapy.

These findings were derived from the phase 3 SERENA-6 trial, data from which was shared in a press briefing at the 

The median investigator-assessed progression-free survival was 16.0 months with camizestrant plus CDK4/6 inhibition (157 patients treated) versus 9.2 months with continued AI/CDK4/6 inhibition (158 patients treated). The 12- and 24-month progression-free survival rates in the camizestrant arm were 60.7% and 29.7%, respectively, versus 33.4% and 5.4% in the continued AI/CDK4/6 inhibition arm.

“SERENA-6 is the first global registrational phase 3 study to demonstrate the clinical utility of circulating tumor DNA [ctDNA] monitoring to detect and treat emerging resistance ahead of disease progression,” Dr. Nicholas C. Turner, lead study author and director of The Royal Marsden and Institute of Cancer and National Institute for Health and Care Research Biomedical Research Centre in London, United Kingdom, said in the press briefing.

Echoing the significance of these findings, Dr. Eleonora Teplinsky,, stated, “When patients progress on scans, we’re already behind. We’re switching therapy, and we’ve already lost control [of the disease]. What this study does is [adopt] an early switch approach before we see disease progression on imaging, allowing us to stay ahead of the curve.” Teplinsky is head of Breast and Gynecologic Medical Oncology at Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, and a clinical assistant professor of medicine at The Icahn School of Medicine at Mount Sinai in New York, New York.

Turner started the presentation by acknowledging the present unmet need for patients with ESR1-mutant, advanced hormone receptor–positive breast cancer. Although rare at diagnosis, comprising less than 5% of advanced cases, ESR1 mutations will develop in approximately 40% of cases, resulting in disease progression on frontline therapy with an AI and CDK4/6 inhibitor.

However, ESR1 mutations can be isolated in ctDNA approximately 6 months before progression. 

Camizestrant is a next-generation oral selective ER degrader and complete ER antagonist that’s designed to inhibit and degrade the mutant and wild-type forms of the ER. Previously, the FDA granted fast track designation to the agent for the population enrolled in SERENA-6. By coupling the use of ctDNA with early integration of camizestrant ahead of disease progression, investigators theorized they could prolong the clinical benefit of frontline treatment.

The randomized, double-blind, placebo-controlled SERENA-6 trial enrolled female and male patients with ER-positive, HER2-negative advanced breast cancer who had received at least 6 months of an AI in combination with a CDK4/6 inhibitor as initial endocrine-based therapy for advanced disease. Patients also needed to have a detectable ESR1 mutation in their ctDNA without evidence of disease progression. 

A total of 3,325 patients who were receiving frontline therapy with an AI and CDK4/6 inhibitor for at least 6 months were screened. ESR1 mutation testing (3,256 patients total) was evaluated in ctDNA with the Guardant360 CDx assay every 2 to 3 months at the time of routine staging scans. A total of 548 patients had detectable ESR1 mutations, 51% of whom were positive on the first test, 38% of whom were positive after two to five tests, and 11% of whom were positive after the fifth test. A total of 233 patients discontinued the study due to screening failure (200 patients) or consent withdrawal, lost follow-up, or other reasons (33 patients).

A total of 315 patients were randomly assigned to 75 milligrams (mg) of camizestrant daily plus continued CDK4/6 inhibition and placebo for the AI or continued AI with anastrozole or letrozole plus CDK4/6 inhibition and placebo for camizestrant. Treatment was continued until disease progression, unacceptable toxicity, and patient withdrawal or death.

The primary end point was investigator-assessed progression-free survival by RECIST 1.1 criteria. Secondary end points included time to second disease progression or death, overall survival, safety, and patient-reported outcomes.

Patients were stratified by visceral disease (yes versus no), detection of ESR1 mutation (mutation detected at first test versus a subsequent test), time from initiation of CDK4/6 inhibition plus an AI to randomization (< 18 months versus ≥ 18 months), and choice of CDK4/6 inhibitor (Ibrance [Palbociclib] versus Kisqali [ribociclib] versus Verzenio [abemaciclib]).

Secondary End Points and Trial Significance

Time to deterioration in global health status/quality of life was also presented. The median time to deterioration according to the European Organization for Research and Treatment of Cancer 30-item quality of life questionnaire was 23.0 months with camizestrant (107 patients) versus 6.4 months with continued AI/CDK4/6 inhibition (95 patients).

Turner noted that the camizestrant regimen also had a low rate of treatment discontinuations resulting from side effects.

“[These data highlight the] potential for a new treatment strategy in oncology to treat developing resistance before it causes progression,” Turner said in conclusion.

Elaborating on the novelty of the study design, Teplinsky explained, “Allowing patients to remain on first-line endocrine therapy for hormone receptor–positive, HER2-negative advanced breast cancer is critical, because we know that outcomes worsen with subsequent lines of therapy. Allowing that longer time on first-line endocrine therapy is significant, and it also improves quality of life, as we’ve seen, and that’s a huge part of living with metastatic breast cancer. [The study] uses a technology, [which] is a liquid biopsy, that doesn’t pose risks of surgical biopsies, and it’s something that can be done and is available in our clinic now. Although camizestrant is not yet FDA approved, this likely will pave the way for a new treatment strategy in first-line hormone receptor–positive, HER2-negative metastatic breast cancer in patients with ESR1 mutations.”

Dr. Julie Gralow, chief medical officer and executive vice president at ASCO, added, “We are using these liquid biopsies [to detect] ctDNA. We have whole sessions at this meeting, looking at using them in colon cancer, but using them to detect emerging resistance before we see evidence of tumor progression on scans is what’s novel about this study.”

Turner N, Mayer E, Park YH, et al. Camizestrant + CDK4/6 inhibitor (CDK4/6i) for the treatment of emergent ESR1 mutations during first-line (1L) endocrine-based therapy (ET) and ahead of disease progression in patients (pts) with HR+/HER2– advanced breast cancer (ABC): Phase 3, double-blind ctDNA-guided SERENA-6 trial. 

. 2025;43(suppl 17):LBA4. doi:10.1200/JCO.2025.43.17_suppl.LBA4

The SERENA-6 trial demonstrated that camizestrant combined with CDK4/6 inhibitors significantly improved progression-free survival in patients with ESR1-mutated, ER-positive, HER2-negative advanced breast cancer compared to continued AI and CDK4/6 inhibitor therapy. This study utilized ctDNA monitoring to detect resistance before disease progression, allowing for an early switch in therapy. The trial highlighted the potential of camizestrant as a new treatment strategy, emphasizing the importance of maintaining patients on first-line endocrine therapy to improve outcomes and quality of life.

Camizestrant and continued therapy with CDK4/6 inhibition benefits patients who present with ESR1-mutated, ER+, HER2– advanced breast cancer. 

Camizestrant and CDK4/6 Inhibition Benefits Outcomes in Breast Cancer Subgroups 

Erleada reduced the risk of death by more than 20% compared with other treatments in metastatic castration-sensitive prostate cancer.

Among patients with metastatic castration-sensitive prostate cancer, treatment with Erleada (apalutamide) showed consistent 24-month overall survival between real-world use and the phase 3 TITAN trial.

These findings were presented at the 50th Annual Oncology Nursing Society Congress. Data reported showed that at 24 months after treatment initiation, patients with metastatic castration-sensitive prostate cancer who were not previously treated with androgen receptor pathway inhibitors (ARPIs) and received Erleada showed a 23% reduction in the risk of death compared with patients treated with Xtandi (enzalutamide); this overall survival result was also consistent when using all available follow-up. Patients treated with Erleada after 24 months post-index had a 26% reduction in the risk of death versus patients treated with Zytiga (acetate); this overall survival result was also consistent when using all available follow-up.

“All three agents have demonstrated statistically significant reductions in disease progression and death as compared with androgen deprivation therapy [ADT] alone in patients with metastatic castration-sensitive prostate cancer in phase 3 trials,” said Kelly Hastings, senior medical science liaison at Johnson & Johnson Innovative Medicine, in a poster presentation of the findings. “However, there are currently no head-to-head studies comparing the survival outcomes [or disease progression] between Erleada and either of the two agents in ARPI-naive patients with metastatic castration-sensitive prostate cancer.”

Androgen receptor pathway inhibitors (ARPI): drugs that block the effects of male hormones on prostate cancer cells, helping slow cancer growth.

Median overall survival (OS): the midpoint survival time where half of patients live longer and half live shorter.

Radiographic progression: worsening of cancer visible on imaging tests like X-rays or CT scans.

In September 2019, the United States Food and Drug Administration (FDA) approved Erleada for the treatment of patients with metastatic castration-sensitive prostate cancer, which was based on data from the phase 3 TITAN trial. Results from the final analysis revealed that Erleada plus ADT led to a 35% reduction in the risk of death compared with placebo plus ADT, with a median overall survival that was not reached versus 52.2 months, respectively.

In December 2019, the FDA approved Xtandi for the treatment of patients with metastatic castration-sensitive prostate cancer, which was based on findings from the phase 3 ARCHES trial. Of note, Xtandi plus ADT significantly reduced the risk of radiographic progression or death versus placebo plus ADT. Moreover, the FDA approved Zytiga with prednisone for high-risk metastatic castration-sensitive prostate cancer in February 2018 based on findings from the phase 3 LATITUDE trial. In the final overall survival analysis of the study, the median OS was significantly longer in the Zytiga cohort at 53.3 months versus 36.5 months in the placebo cohort.

Real-World Treatment Patterns and Study Limitations

In the Erleada versus Xtandi analysis, the median follow-up period was 20.1 months in those who initiated Erleada and Xtandi, respectively. Of note, the median duration of continuous ARPI use, with a 90-day gap between treatments to define discontinuation, was 6.9 months in the Erleada cohort and 6.4 months in the Xtandi cohort.

Based on the Erleada versus Zytiga analysis, the median follow-up period was 19.5 months in patients who initiated Erleada and 19 months in those who initiated Zytiga. Specifically, the median duration of continuous ARPI use, including the 90-day gap in treatments to define discontinuation, was 6.6 months versus 8.9 months in those who initiated Erleada or Zytiga, respectively.

Limitations of this real-world study included the potential for selection and information bias because of miscoding or misclassification in clinical records or claims data, a sole database reflection of a community urology perspective, missing deaths from KRD despite high capture rates of 90% or greater, residual differences post-IPTW associated with a high-risk indication for Zytiga, and the confinement that the regression analysis could only adjust for measured covariates with the potential of remaining confounding variables.

“In phase 3 trials, overall survival was assessed at prespecified time points. In these real-world studies, overall survival was assessed [for] 24 months for evaluation of statistical comparison. Longer follow-up may better estimate the full clinical benefit of Erleada,” the poster authors concluded.

“Real-world head-to-head studies evaluating overall survival with Erleada and Zytiga or Xtandi in patients with metastatic castration-sensitive prostate cancer” by Dr. Neil Shore, et al., 50th Annual Oncology Nursing Society Congress.

“Erleada in patients with metastatic castration-sensitive prostate cancer: final survival analysis of the randomized, double-blind, phase III TITAN study” by Dr. Karim N. Chi, et al., J Clin Oncol.

“ARCHES: a randomized, phase III study of androgen deprivation therapy with Xtandi or placebo in men with metastatic hormone-sensitive prostate cancer” by Dr. Arjun J. Armstrong, et al., J Clin Oncol.

“Zytiga plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomized, double-blind, phase 3 trial” by Dr. Karim Fizazi, et al., Lancet Oncol.

Erleada (apalutamide) demonstrates consistent 24-month overall survival in real-world settings and the phase 3 TITAN trial for metastatic castration-sensitive prostate cancer. Compared to Xtandi (enzalutamide) and Zytiga (acetate), Erleada shows a significant reduction in the risk of death. Despite the absence of head-to-head studies, all three agents have shown significant benefits over androgen deprivation therapy alone. Real-world studies reveal limitations such as potential biases and missing data. Longer follow-up may provide a more comprehensive understanding of Erleada's clinical benefits.

Erleada Reduces Risk of Death in Metastatic Prostate Cancer Subset

The combination of first-line Bavencio and Inlyta was effective and safe in advanced RCC; stock.adobe.com

For patients with advanced renal cell carcinoma (RCC), first-line Bavencio (avelumab) in combination with Inlyta (axitinib) was effective and safe in a real-world population and delivered results consistent with those previously reported in clinical trials, according to findings from the primary analysis of the AVION study, which were presented at the 

At a data cutoff date of July 5, 2024, among patients with advanced RCC in Belgium, Germany, Greece, and Russia enrolled in the trial who received the combination in routine clinical practice (104 patients), the median overall survival (OS) was not reached (NR), the six-month OS rate was 89.1%, and the 12-month OS rate was 82.7%.

“Overall, results from AVION demonstrate the effectiveness, safety, favorable tolerability and stable health-related quality of life [HRQOL] of [Bavencio plus Inlyta] in a heterogeneous real-world population,” lead study author Dr. Axel Stuart Merseburger, and coauthors wrote in a poster of the data.

Palmar-plantar erythrodysesthesia syndrome: a condition with redness and pain on the palms and soles, often from cancer treatment.

Hypertensive crisis: a severe spike in blood pressure, typically over 180/120 mm Hg, risking organ damage.

Complete response (CR): no evidence of cancer after treatment.

Partial response: a significant reduction in tumor size, but not complete elimination.

Stable disease: cancer that hasn't worsened or shrunk significantly.

Progressive disease (PD): cancer that is growing or spreading despite treatment.

Overall survival (OS) rate: the percentage of patients alive after a certain time post-treatment.

Duration of OS: the time from diagnosis/treatment to death or end of study.

Progression-free survival (PFS): the time a patient lives without cancer worsening.

Overall response rate (ORR): the percentage of patients whose cancer shrinks or disappears.

Duration of response (DOR): the time cancer remains controlled after treatment.

Disease control rate (DCR): the percentage of patients with CR, partial response, or stable disease.

Stable health-related quality of life (HRQOL): maintaining a stable quality of life despite disease presence.

Dysphonia: voice changes due to cancer or treatment effects on the vocal cords.

Pruritus: itching, often caused by cancer treatments or malignancy.

ECOG performance status of 0/1 or 2: level of functioning, where 0 indicates no symptoms, 1 means mild symptoms and 2 indicates moderate symptoms limiting some activities.

Merseburger is chairman of the Clinic of Urology at University Hospital Schleswig-Holstein in Lübeck, Germany.

Any-grade side effects (AEs) were observed in 83.7% of patients, and grade 3 (severe) or worse AEs were observed in 34.6% of patients. AEs led to discontinuation of Bavencio or Inlyta in 9.6% and 14.4% of patients, respectively.

Any-grade treatment-related AEs (TRAEs) were reported in 67.3% of patients, and grade 3 or worse TRAEs were reported in 20.2% of patients. TRAEs led to discontinuation of Bavencio or Inlyta in 6.7% and 9.6% of patients, respectively.

The most common TRAEs were diarrhea (any-grade, 26%; grade 3 or worse, 4.8%), fatigue (13.5%; 1.9%), hypertension (10.6%; 1%), hypothyroidism (8.7%; 0%), dysphonia (8.7%; 0%), nausea (7.7%; 0%), palmar-plantar erythrodysesthesia syndrome (7.7%; 0%), pruritus (6.7%; 0%), decreased weight (5.8%; 0%), dyspnea (3.8%; 1.9%) and hypertensive crisis (2.9%; 1.9%).

Serious AEs and serious TRAEs were noted in 36.5% and 14.4% of patients, respectively. A total of 10.6% of patients received corticosteroids, immunosuppressants or hormonal therapy to manage any-grade TRAEs.

AEs led to death in four patients, and TRAEs led to death in one patient.

Previously, the phase 3 JAVELIN Renal 101 trial showed that first-line Bavencio plus Inlyta generated significantly longer progression-free survival (PFS), and higher objective response rates (ORRs) compared with Sutent (sunitinib) and had an acceptable, long-term safety profile in patients with advanced RCC. The final analysis of JAVELIN Renal 101 showed that in the overall population, at a minimum follow-up of 68 months, the median PFS was 13.9 months with the combination versus 8.5 months with Sutent. The ORRs in these respective arms were 59.7% and 32%.

Additionally, outcomes from the final OS analysis in the overall population favored the combination arm, although the OS difference between the two arms was not statistically significant. The median OS was 44.8 months with the combination versus 38.9 months with Sutent.

The findings from JAVELIN Renal 101 supported the 2019 FDA approval of Bavencio plus Inlyta for the first-line treatment of patients with advanced RCC. In 2019, the European Commission also approved the combination for this indication.

Despite these data and approvals, the AVION investigators noted that real-world data with the combination in clinical practice are limited.

The prospective, noninterventional AVION study enrolled patients being treated for locally advanced, recurrent or metastatic RCC in Belgium, Germany, Greece, and Russia who had already received one or two doses of frontline Bavencio plus Inlyta; these patients received further treatment with the combination during AVION. Patients needed to be at least 18 years of age, have histologically confirmed disease with any histological origin, and have an ECOG performance status of 0 to 2.

Patients received Bavencio intravenously at 800 milligrams (mg) every two weeks and Inlyta orally at 5 mg twice daily.

The primary end goal was the OS rate at 12 months from the date of the first treatment received after informed consent. Secondary end points included the 24-month OS rate, duration of OS, PFS, ORR, duration of response (DOR), disease control rate (DCR), safety and HRQOL.

In total, 105 patients were enrolled. One patient did not report Inlyta treatment prior to informed consent and was excluded from the analysis population.

Patients had a median age of 70 years; 34.6%, 40.4% and 25% of patients were younger than 65 years of age, between 65 and 75 years of age and older than 75 years of age, respectively. Most were male (70.2%). Additionally, 89.4%, 3.8% and 6.7% of patients had clear cell, sarcomatoid and other disease histology, respectively. PD-L1 status was negative, positive, not applicable and missing in 16.3%, 5.8%, 28.8% and 49% of patients, respectively. Prior anticancer treatments included adjuvant drug treatment (3.8%), surgery (75%), nephrectomy (66.3%) and radiotherapy (8.7%). At baseline, the median time since initial diagnosis was 0.7 years.

At the last follow-up, 20% of patients were still receiving Bavencio or Inlyta, 20% of patients had discontinued treatment and remained in follow-up, and 60% of patients had discontinued from the study. Reasons for study discontinuation included death (38.1%), completion of the study (28.6%), and loss to follow-up (15.9%).

The median duration of Bavencio treatment was 341 days, and the median duration of Inlyta treatment was 354 days. The median time to discontinuation of both Inlyta and Bavencio was 208 days.

Subgroup analyses of 12-month OS rates showed that among patients younger than 65 years of age, 65 to 75 years of age, and older than 75 years of age, the 12-month OS rates were 85.5%, 84.5% and 75.8%, respectively. Among patients with an ECOG performance status of 0/1 or 2, these rates were 84.3% and 57.1%, respectively. Among patients from Belgium, Germany, Greece and Russia, these respective rates were 87.5%, 86.2%, 71.9% and 95.2%.

Among patients with IMDC favorable-, intermediate-, and poor-risk disease, the 12-month OS rates were 92.6%, 74.1% and 82.5%, respectively. Among patients with clear cell, sarcomatoid, and other histologies, these respective rates were 83.1%, 100% and 66.7%. Patients who had undergone prior nephrectomy (69 patients) had a 12-month OS rate of 86.7% versus 73.4% among those who had not undergone prior nephrectomy (35 patients).

In the overall population, the median PFS was 11.3 months. The six- and 12-month PFS rates were 72.5% and 48.4%, respectively.

Among 87 response-evaluable patients, the ORR was 46%, including complete response (CR), partial response, stable disease, progressive disease (PD), and non-CR/non-PD rates of 4.6%, 41.4%, 31%, 20.7% and 2.3%, respectively. The DCR was 79.3% and the median DOR was NR.

“Real-world effectiveness and safety of first-line (1L) avelumab + axitinib in patients with advanced renal cell carcinoma (aRCC): primary analysis of the AVION study.” by Dr. Merseburger A, et al., 

“Avelumab + axitinib versus sunitinib in patients (pts) with advanced renal cell carcinoma (aRCC): final overall survival (OS) analysis from the JAVELIN Renal 101 phase 3 trial.” by Dr. Motzer RJ, et al., 

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The combination of Bavencio (avelumab) and Inlyta (axitinib) has shown effectiveness and safety in treating advanced renal cell carcinoma (RCC) in a real-world setting, consistent with previous clinical trials. The AVION study reported a six-month overall survival (OS) rate of 89.1% and a 12-month OS rate of 82.7%. Adverse events (AEs) were common, with 83.7% experiencing any-grade AEs and 34.6% experiencing severe AEs. The study highlighted the combination's favorable tolerability and stable health-related quality of life (HRQOL) in a diverse patient population.

In a real-world analysis of patients with advanced RCC, the combination of first-line Bavencio and Inlyta was effective and safe.

Ashley Chan

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