Kristi Rosa

 fusion–positive cell lines, zenocutuzumab (Zeno; MCLA-128) demonstrated blockage of growth and cell death, as well as tumor shrinkage and durable tumor regression in multiple cancers when used in 

 fusion–positive patient-derived xenografts, according to a poster presentation given during the virtual AACR Annual Meeting 2021.

The antibody-dependent cellular cytotoxicity (ADCC)–enhanced anti-HER2/HER3 bispecific antibody was also found to block HER3 phosphorylation and downstream signaling, induce expression of markers of apoptosis and cell cycle arrest, and inhibit expression of cyclin D1.

“Zenocutuzumab effectively blocks the growth of 

 fusion–positive cell lines and xenograft models of tumors arising from the lung, pancreas, and other organs,” lead author Igor Odintsov, MD, research fellow at Memorial Sloan Kettering Cancer Center, and colleagues, wrote in the poster on the data. “In vitro, zenocutuzumab has no significant effect on parental cells and only inhibits viability induced by expression of a 

 fusion. In vivo, [the agent] demonstrated significant efficacy at clinically relevant dose levels illustrating potent therapeutic activity.”

 gene occur at low frequency in pancreatic cancer, lung cancer, and other cancers, according to the study authors. 

 fusion oncoproteins adhere to HER3, resulting in heterodimerization with HER2 and strong activation of downstream signaling that happens mainly through the PI3K/AKT pathway.

Zenocutuzumab, which is manufactured by Merus, was designed to “dock” on HER2 to appropriately position the antibody and then “block” NRG1 from interacting with HER3; this serves to effectively prevent HER2:HER3 heterodimerization and downstream signaling.

Previously, in January 2021, the FDA granted a fast track designation to zenocutuzumab for the treatment of patients with solid tumors that harbor NRG1 gene fusions and have progressed on standard-of-care therapy.

For the study presented during the meeting, investigators set out to examine the efficacy of zenocutuzumab in preclinical models of 

 fusion–positive cancers. To do this, the agent was evaluated in a panel of isogenic and patient-derived cell lines and xenograft (PDX) models of several cancers, including of the lung, breast, and pancreas. Cell lines either expressed an 

 fusion endogenously or by lentiviral transfer of cDNAs.

The models were generated from non–small cell lung cancer samples that harbored 

 (LUAD-0061AS3) fusions, as well as from a high-grade serous ovarian cancer that harbored a 

 fusion (OV-10-0050). Pancreas samples harbored 

 fusion–positive breast cancer, pancreatic cancer, and lung cancer cell lines, investigators noted a reduction of disease growth that was dose dependent. In all of the cell lines that had been evaluated, abrogated phosphorylation of HER3, HER4, AKT, p70S6 kinase, and STAT3 had been observed.

Additionally, phosphorylation of HER2, EGFR, and MEK/ERK was also found to be inhibited with the agent in a cell-specific manner, though with some variation. Notably, treatment with zenocutuzumab did not significantly alter the growth of isogenic control cell lines that did not harbor 

Specifically, in the breast cancer and lung cancer cell lines, the bispecific antibody resulted in the downregulation of cyclin D1 level and elicited expression of the negative cell cycle regulators P21 or P27.

Moreover, in the cells that had been exposed to zenocutuzumab, evidence of apoptosis activation, such as cleaved PARP, expression of BIM and PUMA, was also noted.

When the bispecific antibody was administered at doses of 2.5 mg/kg, 8 mg/kg, and 25 mg/kg every week to mice who had LUAD-0061AS3, ST3204, and OV-10-0050 PDX tumors, dose-dependent inhibition of tumor growth was observed. Notably, tumor shrinkage was noted when the highest dose of zenocutuzumab was administered; this dose was equivalent to the 650-mg, twice-weekly dose that has been identified for humans.

Using a chromium release assay and peripheral blood mononuclear cells, investigators found that the agent induced substantial cytotoxicity in MDA-MB-175-VII cells. Notably, a non-ADCC–enhanced, non-specific IgG was not reported to have any effect.

“These results further support the clinical development of zenocutuzumab by Merus as therapy for [patients with] 

 fusion–driven cancers,” the study authors concluded in the poster.

To this end, the agent will be evaluated in the multicenter, multinational, dose-escalation, phase 1/2 eNRGy trial (NCT02912949).2 Here, investigators will further evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity of the agent in patients with 

1. Odintsov I, Khodos I, Espinosa-Cotton M, et al. The HER2xHER3 bi-specific antibody Zenocutuzumab is effective at blocking growth of tumors driven by NRG1 gene fusions. Presented at: AACR Annual Meeting 2021; April 10-15, 2021; Virtual. Abstract 956.

2. A study of zenocutuzumab (MCLA-128) in patients with solid tumors harboring an NRG1 fusion. ClinicalTrials.gov. Updated January 12, 2021. Accessed April 10, 2021. 

https://clinicaltrials.gov/ct2/show/NCT02912949

Articles

In NRG1 fusion–positive cell lines, zenocutuzumab demonstrated blockage of growth and cell death, as well as tumor shrinkage and durable tumor regression in multiple cancers when used in NRG1 fusion–positive patient-derived xenografts.

Zenocutuzumab Effectively Blocks Growth of NRG1 Fusion-Driven Tumors

In patient with metastatic uveal melanoma, frontline treatment with tebentafusp (IMCgp100) achieved significant and clinically meaningful improvement in overall survival (OS), according to data from the phase 3 IMCgp100-202 trial (NCT03070392) presented during a press briefing ahead of the virtual AACR Annual Meeting 2021.

At a median follow-up of 14.1 months, the median OS with tebentafusp was 21.7 months (95% CI, 18.6-23.6) vs 16.0 months (95% CI, 9.7-19.4) with investigator’s choice of pembrolizumab (Keytruda), ipilimumab (Yervoy), or dacarbazine (stratified hazard ratio [HR], 0.51; 95% CI, 0.37-0.71; 

<.0001). The 1-year OS rates in the investigative and control arms were 73.2% and 58.5%, respectively.

“[Tebentafusp] is the first investigational therapy in a phase 3 trial to improve OS in metastatic uveal melanoma, and this benefit was even seen in patients without RECIST objective response,” Jessica C. Hassel, MD, of the University Hospital Heidelberg in Germany, said in a presentation on the data. “We found a predictable and manageable safety profile, which was consistent with the mechanism of action of tebentafusp. Therefore, [the agent] has the potential to be practice changing in uveal melanoma.”

Uveal melanoma is a rare disease with a low mutational burden and a poor prognosis. Approximately half of these patients will develop metastases in the liver, according to Hassel. Only few patients will derive benefit from immunotherapy agents, and no standard-of-care options are available to those who have metastatic disease. In frontline trials that have been done in patients with this disease, the 1-year OS rate has been about 50%.

Patients with uveal melanoma commonly express the melanocytic protein gp100, Hassel noted. Tebentafusp is a bispecific protein that is comprised of a soluble T-cell receptor that is fused to an anti-CD3 immune-effector domain and is designed to target gp100.

 enrolled 378 patients with previously untreated uveal melanoma. To be eligible for enrollment, patients had to be at least 18 years of age, have histologically or cytologically confirmed metastatic uveal melanoma, be HLA A*0201 positive per central assay, have an ECOG performance status of 0 or 1, and measurable or non-measurable disease per RECIST v1.1 criteria.2 Patients could not have previously received systemic treatment in the advanced setting, nor could they have received liver-directed therapy with the exception of surgery. Any lactate dehydrogenase level (LDH) was permitted.

Participants were randomized in a 2:1 fashion. Those enrolled to the investigative arm received tebentafusp at 20 mcg on day 1 of cycle 1, followed by 30 mcg on day 8 or cycle 1, and then 68 mcg day 15+ of cycle 1. Those in the control arm received either pembrolizumab at 2 mg/kg every 3 weeks, ipilimumab at 3 mg/kg every 3 weeks, or dacarbazine at 1000 mg/me  every 3 weeks. Patients were stratified by LDH (greater than the upper limit of normal [ULN] vs ULN or less).

The co-primary end points of the trial were OS in patients randomized to tebentafusp vs investigator’s choice of treatment in the intent-to-treat population and OS in patents randomized to tebentafusp with rash during week 1 vs investigator’s choice of treatment. Key secondary end points included objective response rate and progression-free survival per investigator assessment.

“[When looking at] the Kaplan Meier curves for the primary end point of OS, you see an early and continuous separation for patients receiving tebentafusp vs investigator’s choice. Of note, most patients in the investigator’s choice arm received pembrolizumab,” Hassel noted when speaking to the efficacy data. “The OS benefit can be seen through all subgroups assessed. Patients with a lower tumor load who had a normal LDH always had a better HR vs those with a higher tumor load.”

The HR between the arms in those with an LDH at the ULN or below was 0.35 (95% CI, 0.21-0.60) vs 0.70 (95% CI, 0.46-1.09) in those with LDH that was greater than the ULN.

Regarding safety, toxicities with tebentafusp proved to be consistent with the proposed mechanism of action of the agent. Almost all, or 99.6% of patients, experienced any-grade adverse effects (AEs); 45% of patients had grade 3/4 effects.

The most frequent any-grade cytokine-mediated AEs reported with tebentafusp was cytokine release syndrome (CRS; 89%), pyrexia (76%), chills (47%), nausea (43%), fatigue (41%), and hypotension (38%). Among those who experienced cytokine-mediated toxicities that were grade 3/4 in severity, 4% had pyrexia, 3% had fatigue, and 3% had hypotension.

Eighty-three percent of patients experienced rash with the agent, while 69% reported pruritus, 29% had dry skin, and 23% had erythema. Eighteen percent of patients had grade 3/4 rash, while 5% had grade 3/4 pruritus.

“Very few severe cases of CRS [were reported]; it only occurred in 2 patients and both continued treatment,” Hassel noted. “The discontinuation rate was, in general, very low in the tebentafusp arm vs the investigator’s choice arm, at 2% vs 4%, [respectively].”

The majority of these AEs occurred within the first few weeks of treatment. Then, they decreased in frequency and severity, Hassel added. Notably, no tebentafusp-related deaths were reported per investigator assessment.

“This study has several firsts,” Antoni Ribas, MD, a professor of medicine, professor of surgery, and professor of molecular and medical pharmacology at the University of California Los Angeles and director of the Tumor Immunology Program at the Jonsson Comprehensive Cancer Center, commented during the briefing. “It’s the first-ever clinical trial improving OS in patients with uveal melanoma. It’s the first T-cell receptor therapeutic that has been successfully developed and it’s the first therapeutic that’s targeting a melanocytic antigen that has shown an improvement in a randomized trial. I think it’s a practice-changing study and we hope to be able to use this in the clinic.”

Tebentafusp has been granted a fast track designation and an orphan drug designation from the FDA, along with a Promising Innovative Medicine designation under UK Early Access to Medicines Scheme.

1. Piperno-Neumann S, Hassel JC, Rutkowski P, et al. Phase 3 randomized trial compared tebentafusp with investigator’s choice in first line metastatic uveal melanoma. Presented at: AACR Annual Meeting 2021; April 10-15, 2021; Virtual. CT002.

2. Immunocore’s tebentafusp demonstrates superior overall survival compared to investigator’s choice in a phase 3 clinical trial of patients with previously untreated metastatic uveal melanoma. News release. Immunocore. November 23, 2020. Accessed April 9, 2021. 

In patient with metastatic uveal melanoma, frontline treatment with tebentafusp achieved significant and clinically meaningful improvement in overall survival, according to data from the phase 3 IMCgp100-202 trial.

Initial Treatment With Tebentafusp Show Significant OS Improvement in Metastatic Uveal Melanoma

A retrospective study has suggested that immunotherapy may have a great survival benefit in the frontline setting for patients with metastatic non–clear cell renal cell carcinoma (RCC) than select targeted therapies. 

Results of the analysis presented during the 2021 Genitourinary Cancer Symposium showed that among 1181 patients with metastatic RCC, the median overall survival (OS) in those who received an immune checkpoint inhibitor–based regimen was 28.6 months (95% CI, 17.4–not reached) versus 19.2 months (95% CI, 16.7-21.9) with a VEGF inhibitor and 12.6 months (95% CI, 10.3-14.5) with an mTOR inhibitor.

Moreover, the median time-to-treatment failure (TTF) in those who received an immunotherapy-based regimen was also longer at 6.9 months (95% CI, 2.8-14.0) versus 5.1 months with a VEGF inhibitor (95% CI, 4.6-5.7) and 3.9 months (95% CI, 3.0-5.1) with an mTOR inhibitor.

In the entire population of patients included in the analysis, the objective response rate (ORR) achieved in those who received an immunotherapy-based regimen was 25%; it was 17.8% in those who received VEGF targeted therapy and 5.8% in those who received mTOR-targeted treatment (

“Immune checkpoint inhibitor–based frontline therapy appears to be associated with improved OS compared to VEGF and mTOR targeted therapy in treatment-naïve metastatic non–clear cell RCC, even after adjustment for International Metastatic RCC Database Consortium [IMDC] risk, histology, and age,” lead study author Jeffrey Graham, MD, of the University of Manitoba, and colleagues, wrote in a poster on the data.

Immunotherapy options have induced impressive activity in patients with metastatic clear-cell RCC; as such, these options have become part of standard frontline treatment. Although non–clear cell RCC represents about 15% of all kidney cancers, findings supporting the efficacy of immune checkpoint inhibitors up front has remained largely limited.

To address this need, investigators launched a study to detail the real-world effectiveness of frontline approaches containing immune checkpoint inhibitors in patients with metastatic non–clear cell RCC.

To perform a retrospective analysis of the IMDC, investigators included all patients who had non–clear cell histology. Patients were categorized into 3 groups based on first-line treatment: single-agent VEGF therapy, single-agent or combination immunotherapy, and single-agent mTOR therapy. For the analysis, investigators looked at outcomes, such as ORR, TTF, and OS.

The median age of the entire patient population was 60.6 years, 65.4% were male, 76.4% had undergone nephrectomy, and 16.6% had sarcomatoid features. The most common histologic subtype across the groups was papillary disease (54.2%), and most patients fell into the intermediate IMDC risk group (55.1%). Across the groups, 25.1% of patients had liver metastases, 34.2% had bone metastases, and 3.6% had brain metastases.

Of the 1181 patients included in the analysis, 78.2% had received VEGF treatment (n = 924), which included sunitinib (Sutent; n = 632; 68.4%), pazopanib (Votrient; n = 171; 18.5%), sorafenib (Nexavar; n = 72; 7.8%), cabozantinib (Cabometyx; n = 12; 1.3%), or other (n = 37; 4%). Moreover, 15.8% had received mTOR inhibitors (n = 186) in the frontline setting, such as temsirolimus (Torisel; n = 141; 75.8%) or everolimus (Afinitor; n = 45; 24.2%).

The remaining 5.5% had received immune checkpoint inhibitor–based therapy (n = 65), which could include nivolumab (Opdivo) and ipilimumab (Yervoy; n = 20; 30.8%), atezolizumab (Tecentriq) plus bevacizumab (Avastin; n = 14; 21.5%), nivolumab (n = 13; 20.0%), pembrolizumab (Keytruda; n = 13; 20.0%), or other (n = 5; 7.7%).

Investigators performed a multivariable Cox regression analysis to adjust for imbalances in prespecified prognostic covariates, such as IMDC risk, histologic subtype, and age. Results revealed that the hazard ratio (HR) for OS between immune checkpoint inhibitor–based therapy and VEGF treatment was 0.58 (95% CI, 0.35-0.94; 

= .03), while it was 0.48 (95% CI, 0.29-0.80; 

= .005) for immunotherapy-based treatment versus mTOR therapy.

Additionally, the HR for TTF with immunotherapy-based treatment versus VEGF therapy was 0.72 (95% CI, 0.72; 95% CI, 0.51-1.0; 

= .06) and it was 0.54 (95% CI, 0.37-0.78; 

= .001) for immunotherapy-based treatment versus mTOR treatment.

When looking at ORR per histologic subgroup, those with papillary disease who received VEGF treatment experienced an ORR of 13.0% versus 3.7% with mTOR therapy and 31.6% with immunotherapy-based treatment (

= .002). In patients with the chromophobe subtype, the ORRs were 20.6% versus 13.6% versus 9.1% in those who received VEGF therapy, mTOR therapy, and an immunotherapy-based regimen, respectively (

= .527). Those with an unclassified disease subtype experienced ORRs of 15.2%, 0%, and 33.3%, respectively (

“The ORR of 25% in the entire population is consistent with the existing literature of immune checkpoint inhibitor therapy in non–clear cell RCC, with lower responses seen in the chromophobe subgroup and higher responses seen in the papillary subgroup,” the authors of the poster wrote. “The study population was predominantly papillary RCC, and the effectiveness of immune checkpoint inhibitor–based therapy in other less common histologic subtypes remains inconclusive.”

The results yielded from the analysis must be confirmed in prospective, randomized clinical trials, the authors concluded.

Graham J, Wells C, Dudani S, et al. Effectiveness of first-line immune checkpoint inhibitors (ICI) in advanced non-clear cell renal cell carcinoma. 

. 2021;39(suppl 6):316. doi:10.1200/JCO.2021.39.6_suppl.316

A retrospective study has suggested that immunotherapy may have a great survival benefit in the frontline setting for patients with metastatic non–clear cell renal cell carcinoma (RCC) than select targeted therapies.

OS Benefit Suggested for Frontline IO Versus TKIs in Metastatic Non–Clear Cell RCC

Results from 2 phase 3 clinical trials showed that use of the investigational gene cell therapy betibeglogene autotemcel (beti-cel) led to durable transfusion independence in 87% of pediatric patients under the age of 18 years with transfusion-dependent beta-thalassemia (TDT) with a median average hemoglobin (Hb) of 11.3 g/dL, according to a presentation given as part of the 2021 Transplantation and Cellular Therapy Meetings.

The transfusion independence was maintained by having a dominant HbA787Q fraction in the blood, lead study author Mark C. Walters, MD, who is also the program director of Blood & Marrow Transplantation, program director of the Cord Blood Program, and medical director of the Jordan Family Center for BMT & Cellular Therapies Research, said during an oral presentation delivered on the data.

Moreover, the median weighted average Hb during transfusion independence was 10.1 g/dL in patients under the age of 12 years (n = 4) and 11.4 g/dL in patients between 12 years of age and 18 years (n = 9).

“Overall, the transfusion independence rate was very similar to the adults examined in the phase studies, which had been 83%,” said Walters. “Ineffective erythropoiesis was improved but not eliminated after beti-cel, and the treatment regimen with the gene therapy in pediatric patients less than 18 years of age had a tolerability profile that was consistent with the known effects of myeloablation with single-agent busulfan.”

Beti-cel was developed with the goal of establishing lifelong, functional adult Hb that permits transfusion independence without the need for a donor. To manufacture the product, stem cells are collected from the patient’s blood and then they are altered by a virus that brings working copies of the beta-globin gene into the cells.

 When the cells are returned to the patient, they are delivered via the bloodstream to the bone marrow; once there, they create healthy red blood cells that, in turn, produce beta-globin.

Currently, the gene therapy is under investigation in two phase 3 trials: HGB-207 (Northstar-2) and HGB-212 (Northstar-3). To be eligible for enrollment, patients had to be 50 years of age or younger and have TDT. Specifically, for HGB-207, patients had to have a non

“These are individuals who have some endogenous Hb production, but not enough to avoid regular transfusions,” noted Walters. HGB-212 enrolled patients with the β0/β0 genotype, which is “more severe, and is characterized by having very little or no endogenous Hb production,” added Walters.

Once the safety and efficacy of the gene therapy was established, investigators expanded the research to include pediatric participation. To this end, 26 patients under the age of 18 years were enrolled to the phase 3 trials; they were broken into 2 subgroups: those less than 12 years of age (n = 14; 8 on HGB-207 and 6 on HGB-212) and those between 12 years and 18 years (n = 12; 6 on HGB-207 and 6 on HGB-212).

These patients proceeded to mobilization with granulocyte colony stimulating factor and plerixafor followed by apheresis. As part of the centralized manufacturing process, CD34-positive cells were selected, hematopoietic stem cells were transduced with BB305 lentiviral vector, and then the cells were cryopreserved.

Once shipped back to the transplant center, patients undergo myeloablative conditioning with single-agent busulfan and then the 24 patients were then infused with the gene therapy; 13 patients younger than 12 years received beti-cel (8 on HGB-207 and 5 on HGB-212), while 11 patients between 12 years and 18 years received the product (6 on HGB-207 and 5 on HGB-212).

The median follow-up following infusion was 15.5 months (range, 1.1-29.5). Patients were monitored for hematological recovery, including recovery in erythroid cells that have HbA787Q, the gene therapy Hb, according to Walters. “There’s a single amino acid substitution that permits this Hb to be measured directly after the drug product has been infused, and also the duration can be established,” noted Walters.

The follow-up for this study is 2 years, although patients are provided with the option to participate in long-term follow-up that will continue through 13 years.

At baseline, 46% of those in the cohort of patients less than 12 years (pediatric cohort) were male, as well as 64% of those in the cohort of patients between 12 years and 18 years (adolescent cohort). The median age at assent in the 2 cohorts was 8 years and 15 years, respectively. “Most of the patients had mild to moderate liver iron loading, but there was no cardiac iron loading,” noted Walters.

β0/β0 genotype in the pediatric cohort versus 64% of those in the adolescent cohort; 23% and 36% of patients, respectively, had the β0/β0 genotype. Only 1 patient had a splenectomy prior to trial enrollment and the majority of participants commenced red cell transfusions within their first year of life, added Walters.

The majority of patients had sufficient stem cells mobilized and collected after only 1 mobilization cycle (86%, pediatric; 83%, adolescent), while a smaller fraction required 2 cycles to collect enough cells for product manufacturing (14% and 17%, respectively). The vector copy number was 2.6 in the pediatric group and 3.3 in the adolescent group, and 70% versus 82%, respectively, had CD34-positive cells transduced. The estimated daily average area under the curve over the course of 4 days was 4164 

Regarding hematological recovery following infusion, no difference was observed between the 2 subgroups. Absolute neutrophil count of greater than 500 cells/

μL or greater was observed at day 26, while platelets of over 20,000 were observed around day 50. “Natural killer cells were the first to recover, and CD4 cells took the longest to recover,” said Walters. “However, all the lymphocytes had recovered by 6 to 9 months post infusion.”

All patients in the adolescent subgroup achieved transfusion independence with beti-cel, with a duration of ongoing independence of 14.9 months (range, 12.2-21.6). Four of 6 patients in the pediatric subgroup achieved transfusion independence, with a duration of 15.2 months (range, 12.3-17.7).

Moreover, the majority of the total Hb was found to be comprised of HbA787Q in patients who achieved transfusion independence, particularly those in the adolescent group. “The younger group had somewhat lower levels of HbA787Q,” noted Walters.

Investigators also evaluated improvement in ineffective erythropoiesis in patients who achieved transfusion independence. “This was expressed as the level of the soluble transferrin receptor in the blood and absolute reticulocyte count,” explained Walters. “In most of the individuals there were improvements, although not all the patients moved back into the normal range.”

The safety profile of beti-cel was as expected following myeloablative busulfan, noted Walters. The most frequently reported non-hematologic grade 3 or higher toxicities included stomatitis (58%), febrile neutropenia (50%), and decreased appetite (21%). Serious adverse effects (AEs) included pyrexia (13%), febrile neutropenia (8%), and neutropenia (8%).

Toxicities determined to potentially be associated with the gene therapy were grade 1 tachycardia (n = 1) and grade 1 abdominal pain (n = 2) on the day of infusion and grade 3 thrombocytopenia (n = 1) following infusion, although this was not determined to be a serious case. Veno-occlusive liver disease was treated with defibrotide in 3 patients; although all cases resolved, 2 of these cases were determined to be serious.

No graft failure was observed, and all participants were alive at last follow-up, Walters concluded.

1. Walters MC, Kwiatkowski JL, Porter JB, et al. Safety and efficacy in pediatric patients with transfusion-dependent β-thalassemia (TDT) receiving betibeglogene autotemcel (beti-cel; LentiGlobin for β-thalassemia) gene therapy in the phase 3 HGB-207 (Northstar-2) and HGB-212 (Northstar-3) studies. Presented at: 2021 Transplantation & Cellular Therapy Meetings; February 8-12, 2021; Virtual. Abstract 122. 

2. Zynteglo: betibeglogene autotemcel. bluebird bio. Accessed February 10, 2021. 

Results from 2 phase 3 clinical trials showed that use of the investigational gene cell therapy betibeglogene autotemcel led to durable transfusion independence in 87% of pediatric patients under the age of 18 years with transfusion-dependent beta-thalassemia.

Kristi Rosa | Authors

Articles

Zenocutuzumab Effectively Blocks Growth of NRG1 Fusion-Driven Tumors

Initial Treatment With Tebentafusp Show Significant OS Improvement in Metastatic Uveal Melanoma

OS Benefit Suggested for Frontline IO Versus TKIs in Metastatic Non–Clear Cell RCC

Beti-Cel Shows Good Activity in Transfusion-Dependent Children With Beta-Thalassemia