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Authors

Enriqueta Felip, MD, PhD, is from the Universitat Autònoma de Barcelona, Spain, section chief at the Vall d'Hebron University Hospital, head of the Vall d' Hebron Institute of Oncology's thoracic tumors group.

Enriqueta Felip, MD, PhD, discusses the phase 3 3475A-D77 study of subcutaneous pembrolizumab plus chemotherapy in metastatic non–small cell lung cancer.

Phase 3 Trial Evaluates SC Pembrolizumab vs IV in NSCLC

ASH 2024 Preview for Community Oncologists: The Show and After Show

The American Society of Hematology (ASH) Annual Meeting and Exposition aims to educate oncology providers across an array of hematologic malignancies, with a focus on novel agents, drugs across the FDA pipeline, and more.

, co-hosts Kristie L. Kahl and Andrew Svonavec offer a glimpse at some of the presentations guaranteed to spark one’s curiosity, spur debate, and enhance the field even further. Some key highlights include:

 Continued advancements in CAR T-cell therapy are expected to revolutionize the treatment of hematologic malignancies.

 Bispecific antibodies, such as Epcoritamab (Epkinly), offer a novel approach to target multiple antigens on cancer cells.

 The assessment of MRD is becoming increasingly important in predicting treatment response and overall survival.

Advances in Acute Lymphoblastic Leukemia (ALL)

Blinatumomab (Blincyto) in pediatric ALL:

 The addition of blinatumomab to chemotherapy has shown promise in improving disease-free survival in high-risk pediatric ALL. This combination therapy may offer a more effective treatment option for young patients.

Acalabrutinib (Calquence) in mantle cell lymphoma (MCL):

 The FDA is set to review the approval of acalabrutinib with bendamustine or rituximab (Rituxan) for previously untreated MCL, based on data from the phase 3 ECHO trial (NCT02972840).

Asciminib (Scemblix) in chronic phase chronic myelogenous leukemia (CML-CP):

 The FDA recently granted accelerated approval to asciminib for newly diagnosed CML-CP. This tyrosine kinase inhibitor has shown favorable safety and tolerability profiles.

 isn't just about data, as the duo also offers food recommendations, tourist attractions and fun activities to partake in, as well as interesting facts about San Diego.

This is just a taste of the wealth of information and inspiration waiting at the 2024 ASH Annual Meeting. Check back for future meeting previews with 

Targeted Oncology co-hosts Kristie L. Kahl and Andrew Svonavec highlight abstracts for community oncologists to look out for at the upcoming ASH Annual Meeting in San Diego, with some additional tidbits to round out the main event.

News

The biologics license application (BLA) of the subcutaneous formulation of nivolumab (Opdivo) coformulated with human hyaluronidase (rHuPH20) has been accepted by the FDA.

Findings from the CheckMate -67T (NCT04810078) support this BLA of subcutaneous nivolumab as the trial met its coprimary pharmacokinetic end points and key secondary end point of overall response rate (ORR) vs intravenous (IV) nivolumab in clear cell renal cell carcinoma.

The FDA has set a Prescription Drug User Fee Act (PDUFA) goal date for December 29, 2024.

The FDA has accepted the BLA of the subcutaneous formulation of nivolumab coformulated with rHuPH20, also known as subcutaneous nivolumab, for all previously approved adult solid tumor indications of nivolumab as a monotherapy, monotherapy maintenance following completion of the combination therapy with nivolumab plus ipilimumab (Yervoy), or in combination with chemotherapy or cabozantinib (Cabometyx).

Results from the phase 3 CheckMate -67T trial of subcutaneous nivolumab support this application. In the trial, experts sought to evaluate subcutaneous nivolumab vs its intravenous (IV) formulation.

 Here, the subcutaneous form demonstrated noninferior pharmacokinetics and efficacy, as well as consistent safety compared with the IV formulation of nivolumab among patients with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who have received prior systemic therapy.

A PDUFA goal date has been set for December 29, 2024. With this, subcutaneous nivolumab shows promise to become the first and only subcutaneously administered PD-1 inhibitor.

“We believe subcutaneous nivolumab has the potential to make a significant difference in the lives of patients, which is reinforced by the FDA’s acceptance of our application,” said Gina Fusaro, PhD, vice president, global program lead, Bristol Myers Squibb, in a press release.

“[Nivolumab] is a foundational PD-1 inhibitor approved for many different types of cancer, and our continued investment in research that puts patients first remains a priority. If approved by the FDA, the subcutaneous administration of nivolumab would provide patients and their physicians with a new option that delivers the same well-known benefits as IV [nivolumab] but with the improved convenience of an injection administered in 3 to 5 minutes rather than a 30- to 60-minute infusion,” Fusaro continued.

The phase 3, randomized, open-label CheckMate -67T trial is exploring subcutaneous administration of nivolumab coformulated with rHuPH20 vs IV nivolumab for the treatment of patients with advanced or metastatic ccRCC who were previously treated with systemic therapy.

In the study, 495 patients were randomly assigned to receive either subcutaneous nivolumab or IV nivolumab. Enrollment was open to patients with a histological confirmation of ccRCC, advanced RCC not amenable to curative or radiation therapy, metastatic RCC, those who received no more than 2 prior systemic therapies, those with intolerance or progression after last treatment regimen within 6 months of randomization, and those with a Karnofsky performance score ≥ 70 at screening.

Experts assessed the coprimary end points of time-averaged serum concentration over 28 days and trough serum concentration at steady-state of subcutaneous nivolumab vs IV nivolumab. A key secondary end point of the trial was ORR.

The study met its coprimary pharmacokinetic end points and key secondary end point of ORR with subcutaneous nivolumab in this patient population.

 Subcutaneous nivolumab was noninferior in regard to time-averaged nivolumab serum concentration over 28 days and steady-state trough serum concentration vs treatment with IV nivolumab. Additionally, subcutaneous nivolumab also demonstrated a noninferior ORR compared with IV nivolumab.

1. U.S. Food and Drug Administration accepts Bristol Myers Squibb’s application for subcutaneous nivolumab (nivolumab and hyaluronidase). News release. Bristol Myers Squibb. May 6, 2024. Accessed May 6, 2024. 

2. Phase 3 Check-Mate -67T trial of subcutaneous nivolumab (nivolumab and hyaluranisade) meets co-primary end points in advanced or metastatic clear cell renal cell carcinoma. News release. Bristol Myers Squibb. October 19, 2024. Accessed May 6, 2024. 

3. A study of subcutaneous nivolumab versus intravenous nivolumab in participants with previously treated clear cell renal cell carcinoma that is advanced or has spread (CheckMate-67T). ClinicalTrials.gov. Updated October 12, 2023. Accessed May 6, 2024. 

https://www.clinicaltrials.gov/study/NCT04810078

The FDA is considering a subcutaneous nivolumab formulation for various solid tumors based on promising data from the phase 3 CheckMate -67T trial. A target action date has been set for December 29, 2024.

Clinical

FDA Accepts BLA for Subcutaneous Nivolumab Across Various Solid Tumors

A 66-year-old woman presented with fatigue and unintentional weight loss​.

CT scan: largest lymph node: 3.2 x 1.9 cm​

PET scan: standardized uptake value (SUV): 3

Splenomegaly: 17 cm along the long axis​

Absolute lymphocyte count (ANC): 55.1 × 10

FISH (fluorescence in situ hybridization): deletion 17p (del[17p])​

The patient is in the unfavorable risk category.

What is the balance between efficacy and safety that leads you to choose between available treatment options for chronic lymphocytic leukemia?​

What are your final thoughts on fixed-duration therapy?

There were some people who chose acalabrutinib [Calquence] plus obinutuzumab [Gazyva]. Can you let us know why and who do you use it for?

I chose it. Part of it had to do with insurance, because that's how it's approved [compared with] ibrutinib [Imbruvica] in the first line. The second part of this was many of the patients with CLL present with hemolytic anemia. At times, I ended up using rituximab [Rituxan] as opposed to obinutuzumab, but [the poll] didn't have that option.

So, you add it in those patients with hemolytic anemia. When you use acalabrutinib, do you use it with obinutuzumab?

I am more familiar with rituximab. I know how to deal with those toxicities. Obinutuzumab is a little tougher for me.

We've shown that rituximab doesn't seem to add anything to ibrutinib.

 We've never seen a head-to-head study of ibrutinib plus obinutuzumab vs ibrutinib monotherapy, but we do have acalabrutinib plus obinutuzumab over acalabrutinib. We extrapolate that obinutuzumab might be a better antibody. But to your point, it does have a lot more toxicities. We see tumor lysis, there are a lot more infusion reactions, and there are a lot of cytopenias. It's not so simple to get started, particularly in people with a lot of disease.

In our practice, we will use rituximab too, particularly in patients with a lot of disease and high WBC counts, because you sometimes find yourself in trouble when you try obinutuzumab. That is not to say that you can't. It's just you have to trust your infusion nurse or your team to monitor those laboratory results and be [watching] patients. But rituximab is sometimes easier; I hear that a lot, and I do use the antibody as well. For patients who are hemolyzing, it's very good at getting control pretty quickly, even though BTK [Bruton tyrosine kinase] inhibitors are also very good at hemolysis too. It just takes a lot longer, a month plus, to start to cool things off and you need some help.

I think most people view these BTK inhibitors similarly. It seems like most are choosing more selective drugs. There is no rhyme or reason other than getting experience and [deciding] that's the one you’re using, because there's no compelling reason to go otherwise. Patient factors and choices and insurance seems like driving the choice of the inhibitor.

Many patients decide to go for fixed-duration therapy. For those patients going to fixed duration with venetoclax [Venclexta] plus obinutuzumab, do you have any thoughts about after finishing the first year? How often you do minimal residual disease [MRD] testing and monitoring?

I check MRD. I use it frequently. I will usually check it at cycle 7, day 1 after the obinutuzumab. Most people are MRD [negative at sensitivity of] 10

. I frequently use the clonoSEQ assay. In New York State, it gets approved. I check it at the end of treatment. One thing that has come from the FLAIR study [ISRCTN01844152] is that we know if you can achieve MRD 10

, the likelihood of being at least MRD 10

 in the bone marrow is highly correlated.

 So I use that to spare people bone marrow [biopsies], and I use clonoSEQ to be able to get below that 10

 in the peripheral blood at that cycle 13, I don't [biopsy the] marrow. I know they're negative in their bone marrow for the most part, and I spare them the toxicity of the marrow [biopsy].

Then I check it on a yearly basis, going forward—not that it's prognostic or predictive, but when you start to see it emerge, and it can be several years later, you set some expectations for when you might need to do something. I don't like to fly blind. If I don't have to, I don't send it a lot. You don't need to do it more than once a year or once every year and a half. Honestly, it doesn't come back quickly, but that's how I incorporate it. If they’re negative at the end, you could feel very comfortable to stop treatment.

The problem is if their [MRD is] positive. 

ortunately, almost nobody is MRD positive at the end of venetoclax plus obinutuzumab, particularly in younger patients. In the CLL14 trial [NCT02242942], 86% of patients were MRD [negative at] 10

So, almost everybody's getting there. These truly resistant patients are pretty rare, and it makes me wonder if they have CLL, if it's not some atypical thing, maybe [something] marginal. It's hard to glean from these small numbers of people who are remaining positive, but there's still a problem on what to do [after] a fixed-duration therapy. There are some data that you could continue therapy and maybe deepen it. Sometimes I offer them 6 more months, but that's how I use it. You don't need to check it more than on a yearly basis after they're negative and stopped.

 Allan previously disclosed roles as consultant for AbbVie Inc.; AstraZeneca Pharmaceuticals LP; Genetech, Inc; Janssen Pharmaceutical Company; KLJ Associates, Inc.; Lilly USA, LLC; professional services for Merck and Projects in Knowledge, Inc, and advisory/scientific board membership for NeoGenomics Laboratories, Inc.

1. Burger JA, Sivina M, Jain N, et al. Randomized trial of ibrutinib vs ibrutinib plus rituximab in patients with chronic lymphocytic leukemia. 

. 2019;133(10):1011-1019. doi:10.1182/blood-2018-10-879429

2. Munir T, Cairns DA, Bloor A, et al. Chronic lymphocytic leukemia therapy guided by measurable residual disease. 

. 2024;390(4):326-337. doi:10.1056/NEJMoa2310063

3. Al-Sawaf O, Robrecht S, Zhang C, et al. Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the randomized phase 3 CLL14 study. 

. 2024;144(18):1924-1935. doi:10.1182/blood.2024024631

During a Case-Based Roundtable® event, John N. Allan, MD, discussed the addition of anti-CD20 antibody and the use of MRD following fixed-duration treatment of chronic lymphocytic leukemia.

Incorporating MRD into Monitoring After Fixed-Duration CLL Treatment

Pobel Translates PEACE-1 Trial Results Into Clinical Practice for mCSPC

Cedric Pobel, MD, medical oncologist, PhD student, Institut de Cancérologie, Gustave Roussy, Paris, France, discusses how the 

 (NCT01957436) support the use of radiotherapy plus standard of care (SOC) and abiraterone for the treatment of patients with low-volume metastatic castration-sensitive prostate cancer (mCSPC).

The open-label, randomized, controlled, phase 3 PEACE-1 study was conducted across 77 hospitals in Europe and used a 2 × 2 factorial design. A total of 1173 male patients with de novo mCSPC were enrolled and randomly assigned to 1 of 4 treatment arms: SOC alone, SOC plus abiraterone, SOC plus radiotherapy, or SOC plus both radiotherapy and abiraterone.

The main findings from the trial revealed that in the SOC plus abiraterone and radiotherapy arm, there was a median rPFS of 7.5 years vs 4.4 years in the SOC and abiraterone alone arm (adjusted hazard ratio [HR] 0.65; 

Cedric Pobel, MD, discusses how the results of the PEACE-1 trial support the use of radiotherapy plus standard of care and abiraterone in low-volume metastatic castration-sensitive prostate cancer.

Enriqueta Felip, MD, PhD

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