The FDA has approved melphalan flufenamide (Pepaxto; melflufen) plus dexamethasone for adults with multiple myeloma whose disease is refractory to 1 or more of each type of agent: proteasome inhibitor (PI), immunomodulary agent (IMiD), and anti-CD38 monoclonal antibody.

“Melphalan flufenamide is a novel and innovative therapeutic option which is active in patients with multiple myeloma who have a refractory disease, and the product has a manageable toxicity”, says Professor Ola Landgren, Chief of Myeloma Program and Leader of Experimental Therapeutics Program, Division of Hematology, Sylvester Comprehensive Cancer Center, University of Miami Health System in Miami, Florida, in a press release. “Melphalan flufenamide will complement existing treatment regimens and contribute to address the growing unmet medical need among patients with relapsed or refractory multiple myeloma.”

The approval is based on findings from the phase 2 HORIZON trial, in which melphalan flufenamde combination elicited a 23.7% overall response rate, with a median duration of response of 4.2 months. The regimen also showed activity in patients with extramedullary disease (41%).

HORIZON included 157 patients with relapsed/refractory multiple myeloma who had 2 or more prior lines of therapy, and were exposed to an IMiD and a PI and were refractory to pomalidomide (Pomalyst) and/or daratumumab (Darzalex). Participants in the study had triple-class refractory disease and/or extramedullary disease (EMD) and/or high-risk cytogenetic features. Their ECOG performance status had to fall between 0 and 2.

Patients enrolled in HORIZON were administered 40 mg of melphalan flufenamide and 40 mg of dexamethasone on day 1, and then 40 mg of dexamethasone on days 8 and 15. Patients who were 75 years or older received 20 mg of dexamethasone instead. Treatment continued in 28-day cycles until disease progression or intolerable toxicity.

“The accelerated approval of PEPAXTO in the US is an important milestone for Oncopeptides, and a major step ahead in fulfilling our mission, to bring hope to patients with difficult-to-treat hematological diseases, through innovative science,” said Marty J Duvall, Chief Executive Officer at Oncopeptides AB, in a press release. “Moving ahead, our focus is to further advance PEPAXTO. We look forward to receiving top line data from the phase 3 OCEAN-study in relapsed refractory multiple myeloma, in the second quarter. The comparative study with pomalidomide, is designed to support a future supplementary New Drug Application to expand the label.”

FDA approves Oncopeptides' PEPAXTO (melphalan flufenamide) for patients with relapsed or refractory multiple myeloma. News release. Oncopeptides AB (publ). February 26, 2021. Accessed February 26, 2021. http://cisn.co/3q2bZgq

Articles

The FDA approved melphalan flufenamide (Pepaxto; melflufen) plus dexamethasone for adults with triple-refractory multiple myeloma.

FDA Approves Melphalan Flufenamide Combo for Triple-Refractory Myeloma

Treatment with chimeric antigen receptor (CAR) T cells has induced unprecedented overall response rates (ORR) and complete response (CR) rates in patients with relapsed/refractory B cell malignancies. However, up to 50% of patients will relapse.1

 International Congress on Hematologic Malignancies, David B. Miklos, MD, PhD, associate professor of medicine (blood and marrow transplantation) at the Stanford University Medical Center, suggested that CAR agents targeting multiple antigens might hold the key to breaking through that resistance.

Previous studies have established several factors associated with relapse following CAR T therapy, including loss of the CD19 antigen and aberration in the CD58 antigen, which helps to activate engineered T cells and assists in killing cancer cells.

In a presentation at the 2018 American Society of Hematology Annual Meeting, Jean Oak, PhD, and colleagues found that 8 of 22 (36%) of patients with refractory B cell lymphomas who did not respond to treatment with axicabtagene ciloleucel (Axi-cel) or relapsed after day 28. Five patients (62%) who failed therapy had loss or downregulation of CD19, suggesting that single target antigen loss is a common mechanism of CAR T failure.2

Majzner et al analyzed CD58 status in 51 patients who were treated with axicabtagene ciloleucel for relapsed/refractory B cell lymphomas. Twelve (24%) patients had CD58 mutation or lack of expression, and 11 of those 12 had progressive disease.3

Studies have found CD4+ expression is an indication of patient response. For example, Zinaida Good, PhD, and her colleagues conducted a study seeking to identify cell features distinguishing patients with diffuse large B cell lymphoma (DLBCL) who had durable complete response (CR) at 6 months following axicabtagene ciloleucel treatment from those who had progressive disease. They found that the presence of CD4+ cells on day 7 was highly associated with clinical outcome at 6 months.4

At Stanford, investigators have been experimenting with a bispecific bivalent, single polypeptide called a “loop CAR” over the past 4 years to overcome antigen loss. Miklos showed data from a phase 1 dose escalation study of a bispecific anti CD19/CD22 using a self-contained prodigy production system to generate CAR T cells for patients with acute lymphoblastic leukemia (ALL; n = 17), primary mediastinal B-cell lymphoma (PMBCL; n = 2), and DLBCL (n = 20).

“We had day 28 overall response rates in patients with ALL of 100% and we had complete response of 88%,” Miklos said. “The Kaplan-Meier curve shows that the lymphoma fall off after 6 months was somewhere around 50%, but in truth it’s 29%. In truth, we don't think that the lymphoma responses are competitive with the commercially available products.”

Furthermore, 36% of patients with DLBCL or PMBCL and 50% of those with ALL have relapsed. Stanford, and other groups, will reapproach multi-antigen targeting with new constructs and strategies, Miklos said. There is still an unmet need for a commercially available therapy for adults with relapsed/refractory ALL.

Other investigators, however, are have some success. Nirav N. Shah, MD, and colleagues administered bispecific anti-CD20, anti-CD19 (LV20.19) CAR T cells for relapsed/refractory B cell non-Hodgkin lymphoma or chronic lymphocytic leukemia. Eighteen of 22 patients (82%) had an overall response at day 28 with a CR rate of 64%.5 This was a phase 1 dose escalation and expansion trial that to evaluate safety, as well as the feasibility of on-site manufacturing using the CliniMACS Prodigy system.

Cai Q, Zhang M, Li Z. Potential strategies against resistance to CAR T-cell therapy in haematological malignancies. 

Oak J, Spiegel JY, Sahaf B, et al. Target antigen downregulation and other mechanisms of failure after axicabtagene ciloleucel (CAR19) therapy. 

 2018;132(Suppl 1): 4656. doi:10.1182/blood-2018-99-120206

Majzner RG, Frank MJ, Mount C, et al. CD58 aberrations limit durable responses to CD19 CAR in large B cell lymphoma patients treated with axicabtagene ciloleucel but can be overcome through novel CAR engineering. Presented at: the 62nd ASH Annual Meeting and Exposition; December 5-8, 2020. Abstr 556.

Good Z, Spiegel JY, Sahaf B, et al. Identification of two CAR T-Cell populations associated with complete response or progressive disease in adult lymphoma patients treated with Axi-Cel. 

 2019;134 (Suppl 1):779. doi:10.1182/blood-2019-130815

Shah, NN, Johnson, BD, Schneider D, et al. Bispecific anti-CD20, anti-CD19 CAR T cells for relapsed B cell malignancies: a phase 1 dose escalation and expansion trial. 

.2020;1569–1575. doi:10.1038/s41591-020-1081-3

This article was originally published on OncLive as, "

Multi-Agent Therapy May Overcome CAR T Resistance in B Cell Malignancies

Up to 50% of patients with B-cell malignancies will relapse on CAR T-cell therapy. Investigators are looking in to new ways to overcome that drug resistance.

Overcoming CAR T Resistance in B-Cell Malignancies

The FDA has granted a breakthrough therapy designation to tipifarnib for use in patients with recurrent or metastatic 

-mutated head and neck squamous cell carcinoma (HNSCC) with variant allele frequency (VAF) of 20% or higher following progressive disease on platinum-based chemotherapy.1

The decision is based on findings from the phase 2 RUN-HN trial (KO-TIP-001; NCT023383927) presented during the 2020 ASCO Virtual Scientific Program, in which tipifarnib elicited an objective response rate (ORR) of 50.0% (95% CI, 26.0%-74.0%) in response-evaluable patients with 

“We are very pleased that the FDA has awarded breakthrough therapy designation to tipifarnib, and we appreciate the agency’s affirmation of its potential to treat this devastating disease,” Troy Wilson, PhD, JD, president and chief executive officer of Kura Oncology, stated in a press release. “We remain focused on conducting our AIM-HN registration-directed trial and look forward to working closely with the FDA to bring this therapy to patients as soon as possible.”

The trial enrolled patients with solid tumors that harbored 

 mutations. The first stage of the trial comprised 2 cohorts: patients with thyroid cancer (n = 13) and patients with a solid tumor other than thyroid cancer (n = 13).

For the second stage of the trial, those in cohort 2 who had HNSCC moved into a HNSCC extension cohort, which could enroll up to 30 patients. Cohort 3 was also added, and this would enroll up to 20 patients with tumors other than HNSCC. Here, patients had to have a 35% or higher 

 VAF with serum albumin of 3.5 g/dL or higher.

To be eligible for enrollment, patients could not have any curative therapeutic option available to them, they had to have a tumor harboring a 

 mutation, measurable disease per RECIST v1.1 criteria, and an ECOG performance status of either 0 or 1.

In the second stage of the trial, patients were given oral tipifarnib at a twice-daily dose of 600 mg on days 1 through 7 and days 15 through 21 as part of 28-day treatment cycles.

The primary end point of the trial was ORR achieved with tipifarnib, while the secondary end point was safety and tolerability. Investigators examined progression-free survival (PFS) and duration of response (DOR) as exploratory end points.

A total of 21 patients were enrolled to the trial at the time of the presentation and 20 of them received treatment. Eighteen patients were determined to be evaluable for efficacy. The median age of study participants was 64 years, 66.7% were male, and in 52.4%, the primary tumor location was the oral cavity. Patients received a median of 2 previous anticancer regimens, and these treatments included platinum-based chemotherapy (90.5%), immunotherapy (61.9%), and cetuximab (Erbitux; 52.4%). Approximately 30% of patients were positive for human papillomavirus.

Additional results revealed that the median DOR with tipifarnib was 14.7 months. Moreover, the median PFS with the agent was 5.9 months (95% CI, 3.5-19.2), and the last previous line of treatment was 2.8 months (95% CI, 1.1-5.2). The median overall survival reported with tipifarnib was 15.4 months (95% CI, 7.0-46.4).

Tipifarnib is also under examination in the international, multicenter, open-label, 

 (KO-TIP-007; NCT33719690) in patients with 

-mutated HNSCC. Investigators seek to determine the ORR of tipifarnib in these patients; they will also retrospectively evaluate how the ORR to frontline treatment compares between the accrued patients with 

-mutated disease and matched-case control patients with 

The agent is also examination in patients with 

-mutated urothelial carcinoma (IST-01; NCT025335650).

Kura Oncology receives FDA breakthrough therapy designation for tipifarnib in head and neck squamous cell carcinoma. News release. Kura Oncology, Inc. February 24, 2021. Accessed February 24, 2021. 

Ho AL, Hanna GJ, Scholz CR, et al. Preliminary activity of tipifarnib in tumors of the head and neck, salivary gland and urothelial tract with HRAS mutations. 

. 2020;38(suppl 15):6504. doi:10.1200/JCO.2020.38.15_suppl.6504

FDA Grants Breakthrough Therapy Designation to Tipifarnib for HRAS-Mutated HNSCC

The FDA has granted a breakthrough therapy designation to tipifarnib for use in patients with recurrent or metastatic HRAS-mutated head and neck squamous cell carcinoma with variant allele frequency of 20% or higher following progressive disease on platinum-based chemotherapy.

Tipifarnib Gets Breakthrough Therapy Designation for HRAS-Mutated HNSCC

Advanced practice providers are essential in treating patients with genitourinary cancers, especially as there is a shortage of clinicians in this space. 

Meredith E. Donahue, APRN-BC, shares how her career path brought her to urology, the numerous ways she supports a urology department, and how others may pursue a similar professional focus. Donahue is an advanced practice registered nurse in the Department of Urology at Vanderbilt University, Nashville, Tennessee. She was interviewed by 

™ Editor-in-Chief Raoul S. Concepcion, MD, FACS, director of the Comprehensive Prostate Center and clinical associate professor of urology at Vanderbilt University School of Medicine.

Please explain how you ended up in urology. Did you receive specialized training after obtaining your master of science in nursing?

After graduating from Furman University [in Greenville, South Carolina], with a bachelor’s in science, I was open to any job options when I landed at Urology Associates in Nashville, Tennessee. After my initial exposure to urology, I realized this is where I wanted to spend the rest of my career practicing.

When I started my master’s, I tried my best to experience every part of medicine but ultimately found myself coming back to urology, and specifically urologic oncology. When it came time to figure out next steps and what to do with a master’s, it was obvious that a urology nurse practitioner (NP) fellowship was the best next step for me. Fortunately, I was accepted to Vanderbilt University Medical Center’s Department of Urology NP Fellowship, where I was able to receive a year of specialized training in urology.

There are multiple ways to become an APP. For NPs, one must have a bachelor’s in nursing or any bachelor of science [degree], a registered nurse license, and complete a master of science in nursing. … For physician assistants (PAs), one completes a bachelor’s degree in any field and then completes a master’s program. Both tracks prepare students to [work with] patients as generalists but offer little to no specialty training unless sought out by the student. Thus, making the transition into a specialty like urology may be quite difficult.

That’s where APP fellowships have proved to be pivotal in training APPs in specialty practice to be confident and independent providers. There are only a handful of urology APP fellowships across the country, so it is not reasonable to think all APPs can be trained in that way. It is important to provide adequate onboarding and education for APPs starting a new position in a specialty. With that said, it is exciting to be a part of this growing field of urology APP fellowships.

My now-colleague Gilbert Comola [ANP, CURN], who also completed an APP fellowship in urology, is the director of the fellowship and worked with the Office of Advanced Practice to develop a comprehensive training program in urology that includes spending time with each subspecialty of urology in the outpatient setting and in the operating room, as well as providing inpatient care to primary urology patients and consults. In the fellowship, I was also given dedicated time with our physicians to learn how to perform cystoscopies. With this skill, I can perform hematuria evaluations and stent pulls, or [can] address acute concerns that may require Foley [catheter] placement under cystoscopic guidance. In the fellowship, I had required didactic work as well as attendance at weekly conferences and lectures. This correlated with what I was learning clinically and has ultimately kept me eager to continue attending these educational opportunities beyond the fellowship.

What is your current position in the Department of Urology at the Vanderbilt University School of Medicine?

I am a nurse practitioner in the department of urology and more specifically with our oncology team. I primarily support Joseph Smith, MD, and David Penson, MD. I have my own template every day, but when Dr Smith and Dr Penson are in clinic, I help support them by seeing patients and obtaining new patient histories, and by keeping the patient flow moving. I am also fortunate to share patients with all our urologic oncology [physicians]: Sam Chang, MD; Amy Luckenbaugh, MD; Dan Barocas, MD; and Kelvin Moses, MD. I am lucky to work with all these physicians because I can continue to learn from each of them in different ways.

My current position is all outpatient, working 5 days a week with 1 administrative day. Typically, I spend this time catching up on notes, fielding the urgent/emergent calls for my patients and my MDs, following up on results, and performing peer-to-peer consults. At this point, APPs in our clinic do not take any call.

What are your daily clinical responsibilities as they relate to patients with genitourinary (GU) cancer?

Most of my days are seeing new, return, and postoperative patients. These visits are interspersed along with following up on labs, imaging, and managing urgent and emergent calls from my patients and the patients of the physicians I primarily work with. I also spend half a day seeing patients in our advanced prostate cancer clinic with Dr Moses as well as half a day running our BCG clinic, instilling different intravesical therapies. All these roles certainly keep me busy and challenge me every day.

What challenges has the coronavirus disease 2019 (COVID-19) pandemic lockdown created in helping your patients with cancer, and how have you overcome these?

At the start of the pandemic, the most difficult part was patients asking us whether they were at higher risk by coming to Vanderbilt versus higher risk by delaying surveillance imaging, treatments, or addressing onset signs/symptoms. At the beginning, we didn’t have answers to these questions; I don’t think anyone did. Fortunately, our team quickly learned how to adjust and appropriately guide our patients to keep them safe during the pandemic but also safely and appropriately manage their GU malignancy. Of course, this wasn’t easy. This required our team and me to learn and stay up to date on all the ever-changing COVID-19 data.

You may not have asked, but for every challenge during this time, I like to find the silver linings. During this pandemic, I have found patients to be more open to discuss how they are feeling physically … emotionally and mentally about their health and diagnosis. In my (biased) opinion, [receiving a diagnosis of] a GU malignancy is one of the most vulnerable diagnoses a patient can encounter. It’s always a special moment when I see that wall come down, that wall of fear and embarrassment having to discuss not only a malignancy but also parts of their body they may have never talked about before. I think this pandemic has shown patients and even our society that it is OK to talk with health care providers about how you are feeling both physically and emotionally. It is exciting to see this shift and is a reminder that cancer is not just a diagnosis of their physical body but also of the patient’s mental and emotional health.

Can you think of situations in which, because of your training, APPs can be better utilized to enhance quality and efficiency of care for patients with GU cancer?

Although I am a GU oncology NP, there are numerous adverse events (AEs) from the management of these malignancies that require input from other disciplines of urology, including voiding dysfunction, sexual medicine, and endourology, requiring me to have knowledge in each of these areas. Having training in all of urology during my fellowship has given me the tools and confidence to manage these issues on my own and the understanding of when to refer for a higher level of care. For example, the most common AEs of radical prostatectomy are urinary incontinence and erectile dysfunction. The fellowship allowed me to learn from our experts in each of these areas to appropriately manage patients on my own and [to gain] an understanding of when to advance the level of care for possible surgical therapies. So I can confidently manage a postprostatectomy PSA [prostate-specific antigen] but also any other urologic concerns that arise post-therapy. Another benefit that I and one of my supervising physicians, Dr Smith, identified is that I am able to commit more time to management of these significant life-altering issues and formulate surveillance plans for our patients, ultimately allowing him more time for new patients, operating, or seeing our more complex patients.

Regarding managing postsurgical complications in this population, having spent time in the operating room as well as with our inpatient service has given me invaluable tools to acutely take care of patients in the possible urgent/emergent concerns in the postoperative period. It gave me awareness to know what I can manage in the outpatient versus when to admit someone for inpatient care.

Over the next 5 years, how do you think the role of the APP will evolve, given the advancement of diagnostic testing and plethora of new therapies (and indications) across the various tumor types?

It is certainly an exciting time, witnessing and being a part of the advancements in diagnostic tests as well as novel therapies in urologic oncology. APPs are and will continue to be critical in the implementation and education for patients during the advancement of new tests and therapies.

During the past few months, I have worked closely with our medical oncology team and the hereditary cancer clinic to bring germline testing into the urology clinic for [patients at high risk of prostate cancer who] qualify based on the latest NCCN [National Comprehensive Cancer Network] guidelines. As an APP, I have the time to both set up the logistics of having a new test to offer as well as the time to spend with patients educating them on germline testing in high-risk prostate cancer. There have certainly been logistic hurdles along the way with incorporating a new test into our flow of these, but I have been fortunate to work with a multidisciplinary team to make this process both easy to understand and streamlined for our patients. As we mature our process in offering genomic testing in the urology clinic, our hope is that this multidisciplinary approach can be adopted at other institutions nationwide. Across urologic oncology, there are new and developing testing and therapies, including prostate-specific membrane antigen scanning, blue light cystoscopy, and novel intravesical treatments. With these complex advances comes the increasing need for a team-based approach in the care of our patients. The APP plays a special role as a medical provider closely working with the physician in management, as the patient advocate, and as a liaison for the multidisciplinary approach that these advances will require us to take.

Of course, this will require APPs to stay prudent on learning these changes and updates. We have all our APPs join the American Urological Association, which has vast amounts of education, lectures, and of course guidelines. Likewise, we encourage having NCCN accounts as well as memberships in the Society of Urologic Nurses and Associates and other groups to keep ourselves educated on the quickly changing landscape of urologic oncology.

You are employed in a very highly specialized academic environment. What do you think would be the major critical pieces that independent urology groups should be considering in order to incorporate APPs into their advanced cancer care model?

APP utilization in urology is a topic that [many of my colleagues and I] are always working to improve and maximize. Before incorporating APPs into advanced cancer care, it is critical to start early with adequate education and training. As APPs, we are trained in primary care, where we learn how to medically manage patients. But making the transition to specialize and focus on a particular discipline can be a difficult task. That is where urology groups must take responsibility to provide adequate time and resources for newly hired APPs (those who did not complete a fellowship) to learn how to confidently manage the breadth of urology patients, and in this case urologic oncology patients. My APP colleagues and I have created a formal onboarding plan for newly hired APPs that requires more work on the front end but ultimately pays off when we have a new APP who can function independently.

Having worked in an independent urology group prior to becoming an NP, I have a good sense of the similarities and differences of independent groups versus academic urology. Regarding utilization of APPs, I don’t think our roles differ drastically. In independent urology groups, APPs likely work more as general providers [because] the physicians tend to see all areas of urology. If independent urology groups want to specialize their APPs into oncology roles, there are certainly efficient ways to do so.

Once you have an appropriately trained APP, the options for incorporating them into your advanced cancer care model are endless. An easy way to incorporate APPs into your model is to have the APP see the returns and [patients undergoing routine cancer surveillance]. This could be seeing patients for routine PSA monitoring or surveillance imaging and labs for patients with a history of urothelial carcinoma or renal neoplasms. This allows our MDs more time to see the new patients, the more complex patients, and even more time in the operating room. We even take advantage of this model in our advanced prostate cancer clinic. For example, patients [doing well on therapy whose PSA is stable], I can see … independently, draw labs, give any injections, address AEs/concerns, and send on their way, ultimately leaving Dr Moses more time with our new and more complex patients who often require extensive counseling and evaluation.

Again, in our model at Vanderbilt, our BCG/intravesical therapy clinic is managed by an APP. This includes not only giving patients their treatments but also managing adverse events, questions, and concerns from the patients. This is an excellent way to utilize APPs, because intravesical therapies often come with a host of AEs that must be medically managed. Likewise, having an APP run an intravesical therapy clinic gives patients another provider who understands their pathology, diagnosis, and scheduled treatment plan.

An nurse practitioner discusses how she supports multiple providers in a large academic practice.

APPs Are Key in GU Cancer Care

The FDA has approved the PD-L1 IHC 22C3 pharmDx assay, developed by Agilent Technologies Inc, for expanded use in patients with non–small cell lung cancer (NSCLC).

The assay can now be utilized to help identify patients who may be candidates for treatment with 

cemiplimab-rwlc (Libtayo), which was granted FDA approval

 on February 22, 2021, for use as a single agent in the first-line treatment of patients with advanced NSCLC who have a PD-L1 tumor proportion score of 50% or higher.

The regulatory decision was based on findings from an analysis of 710 patients with a PD-L1 expression of 50% or higher who were randomized to receive cemiplimab in the phase 3 EMPOWER-Lung 1 trial (NCT033088540). Here, the agent resulted in a 32% reduction in the risk of death compared with chemotherapy. Specifically, the median overall survival (OS) in the investigative arm was 22 months versus 14 months with chemotherapy (HR, 0.68; 95% CI, 0.53-0.87; 

Moreover, the median progression-free survival (PFS) with cemiplimab was 6.2 months per blinded independent central review compared with 5.6 months with chemotherapy (HR, 0.59; 95% CI, 0.49-0.72; 

The survival benefit associated with cemiplimab was reported across all subgroups evaluated in the trial, with the exception of OS in female patients.

“Anti–PD-1 therapies, including [cemiplimab], continue to broaden the potential for the treatment of patients across different cancer types,” Sam Raha, president of Agilent’s Diagnostics and Genomics Group, stated in a press release. “With the FDA approval of PD-L1 IHC 22C3 pharmDx as a companion diagnostic for treatment with [cemiplimab] monotherapy in advanced NSCLC, Agilent further strengthens its ability to elevate pathologist confidence in reporting results to oncologists and bolsters our role as a global pioneer in developing companion diagnostics for targeted treatments.”

The multicenter, open-label, phase 3 trial evaluated cemiplimab monotherapy compared with investigator’s choice of platinum-doublet chemotherapy in the frontline treatment of patients with advanced NSCLC whose tumors had a PD-L1 expression of at least 50%. The PD-L1 IHC 22C3 pharmDx was used to examine PD-L1 status in those enrolled to the trial. PD-L1 expression was evaluated in formalin-fixed, paraffin-embedded tumor samples at a central laboratory.

To be eligible for inclusion, patients had to be aged 18 years or older, have histologically or cytologically confirmed stage IIIB or IIIC or stage IV squamous or nonsquamous NSCLC with a PD-L1 expression of at least 50%, and ECOG performance status of 0 or 1, adequate bone marrow and organ function, as well as at least 1 measurable lesion per RECIST v1.1 criteria.

Patients who were never smokers or who had active or untreated brain metastases were excluded. Moreover, if patients had tumors that harbored 

 fusions, they could not participate. Anyone with active, known, or suspected autoimmune disease that needed systemic treatment within the previous 2 years or who had uncontrolled hepatitis B or C infection or human immunodeficiency virus, did not participate.

The primary end points of the trial included OS and PFS, while secondary end points comprised objective response rate (ORR), duration of response, health-related quality of life, and safety with cemiplimab versus chemotherapy. The pharmacokinetics and immunogenicity of the agent is also under exploration.

A total of 3662 patients were screened for the trial and 720 patients met the eligibility criteria. Notably, 74% of patients who experienced disease progression on chemotherapy were given cemiplimab as a crossover treatment. Thirty-two percent of patients who had progressive disease on cemiplimab went on to receive extended treatment with the addition of chemotherapy.

A total of 563 patients comprised the population of patients who had a PD-L1 expression of 50% or higher. The median age of these patients was 63.5 years and just under half, or 46.5%, were aged 65 years or older. Moreover, 85.5% were male, 76.5% were from Europe, and 73% had an ECOG performance status of 1. Additionally, 65% of patients were past smokers, 57% had nonsquamous histology, and 12% had brain metastases.

In this population, the overall median duration of follow-up was 10.8 months for cemiplimab and 10.9 months for chemotherapy. Just under half, or 46%, of patients were still receiving cemiplimab and 16% of patients were still receiving chemotherapy at the time of data cutoff.

The intent-to-treat (ITT) population (n = 710) was comprised of the 563 patients with a PD-L1 of at least 50% and a total of 56 patients who definitively had a PD-L1 expression of less than 50%. The overall median duration of follow-up with cemiplimab and chemotherapy was 13.1 months each.

In the ITT population, cemiplimab also demonstrated an improvement in OS versus chemotherapy, at 22.1 months (95% CI, 17.7–not evaluable) and 14.3 months (95% CI, 11.7-19.2), respectively (HR, 0.68; 95% CI, 0.53-0.87; 

= .0022). Cemiplimab was also found to improve PFS compared with chemotherapy, at a median of 6.2 months (95% CI, 4.5-8.3) versus 5.6 months (95% CI, 4.5-6.1), respectively (HR, 0.59; 95% CI, 0.49-0.72; 

Twenty-eight percent of the 355 patients who received cemiplimab experienced grade 3/4 treatment-emergent adverse effects (TEAEs), and pneumonia (5%) was the most commonly reported effect, followed by anemia (3%), and hyponatremia (3%). Grade 3/4 TEAEs were observed in 39% of those who received chemotherapy; anemia was experienced by 16% of patients, neutropenia presented in 10%, and thrombocytopenia occurred in 8%.

Agilent PD-L1 IHC 22C3 pharmDx receives expanded FDA approval in non-small cell lung cancer (NSCLC). News release. Agilent Technologies Inc. February 22, 2021. Accessed February 23, 2021. 

Sezer A, Kilickap S, Gümüs M, et al. Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. 

. 2021;397(10274):592-604. doi:10.1016/S0140-6736(21)00228-2

FDA Approves Companion Diagnostic for Cemiplimab in NSCLC

The FDA has approved the PD-L1 IHC 22C3 pharmDx assay, developed by Agilent Technologies Inc, for expanded use in patients with non–small cell lung cancer.

FDA Approves Companion Diagnostic for Cemiplimab in Lung Cancer

The FDA has accepted and granted a priority review designation to the biologics license application for Vicineum for use in patients with high-risk Bacillus Calmette-Guérin–unresponsive non–muscle invasive bladder cancer.

Vicineum Granted Priority Review for High-Risk, BCG-Unresponsive Bladder Cancer

Patients with metastatic urothelial carcinoma with higher tumor mutational burden and who experienced immune-related adverse events tended to have higher response rates to immune checkpoint inhibitor. 

High TMB, Adverse Events May Predict Immunotherapy Response in mUC 

The FDA has granted priority review to sotorasib for the treatment of patients with KRAS G12C–mutated locally advanced or metastatic non–small cell lung cancer, after at least 1 previous systemic therapy.

Sotorasib Granted Priority Review for KRAS G12C–Mutated Advanced or Metastatic NSCLC

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FDA Approves Melphalan Flufenamide Combo for Triple-Refractory Myeloma

Overcoming CAR T Resistance in B-Cell Malignancies

Tipifarnib Gets Breakthrough Therapy Designation for HRAS-Mutated HNSCC

APPs Are Key in GU Cancer Care

FDA Approves Companion Diagnostic for Cemiplimab in Lung Cancer

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