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Omar Mian, MD, PhD, provides an overview of the RAD-SG trial of RADiation therapy given with sacituzumab govitecan for bladder preservation in patients with muscle-invasive bladder cancer, which is currently in progress.

RAD-SG Trial Evaluates RADiation Therapy and Sacituzumab Govitecan in MIBC

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 48-year-old woman with T1N1 triple-negative breast cancer (TNBC) received adjuvant ddAC-paclitaxel, which she tolerated well. Eight months after completion of adjuvant therapy, she reported worsening fatigue. ​Laboratory results showed 1.5 times elevated levels of alanine transaminase and aspartate transaminase above the upper limit of normal, and a CT scan showed 1 liver lesion and 2 left lung lesions. A biopsy of the liver lesion confirmed recurrent metastatic TNBC. A brain MRI was negative for brain metastases.

Genetic panel testing was negative for all detectable mutations. PD-L1 expression on immune cells was 0%. The patient was otherwise healthy with no significant comorbidities and had an ECOG performance score of 0.

If you chose chemotherapy or other, what agent/regimen are you most likely to recommend?

 What therapy would you offer this younger woman with metastatic TNBC, who presents with recurrent disease 8 months after completing adjuvant therapy? It looks like a pretty even split between intravenous [IV] single-agent chemotherapy or offering the patient a clinical trial, and one vote each for oral chemotherapy or other.

For the person who voted for other, could you comment on what you might recommend for that patient?

 I was thinking of any immunotherapy, if eligible.

 Would you offer immunotherapy to someone who had PD­-L1-negative TNBC?

 I wouldn’t, but it’s a consideration.

 What single-agent chemotherapy would most of you offer the patient? What are typical strategies that you might use?

 Single-agent carboplatin [is an option].

 Would anyone else consider that for their patients? Would anyone offer doublet therapy? I don’t know if that was an option for anyone.

 With visceral disease and a high burden of disease, carboplatin/gemcitabine would be a choice I would lean towards.

 I agree. I think platinum-based chemotherapy is a good selection and I would prefer gemcitabine/carboplatin.

 I use that a fair bit in my practice as well. What clinical trials are you offering to these patients? What’s interesting out there that you all have in your practices that would be reasonable to offer? Just referring to a trial or treating in-house? I don’t know if anyone has something interesting that they’re excited about in this space.

 I think there are some PARP inhibitor trials out there.

 In part of the US Oncology Network, we have some novel immunotherapies in the basket of diseases including TNBC. But given the lack of phase 2 studies with higher numbers, I would not do it in the first line.

 I would think of genomic testing for this patient to see if the patient is microsatellite instability-high or if it’s 

 I think those are certainly reasonable options. Would anyone else do next-generation sequencing [NGS] on the tumors as well? I believe this patient had germline testing which was negative. But I agree. There was no comment made about NGS.

 I would use germline testing because I send my patients to the University of Chicago Medicine. There’s a 15% chance of a certain abnormality and they have a study for it. I would check for that.

Would your frontline approach differ if relapse occurred 24 months after adjuvant therapy?

This is a slightly different take on the same patient. Again, a 48-year-old woman with metastatic TNBC. BRCA1- and BRCA2-negative, PD-L1-negative. But her disease recurs 2 years after the completion of adjuvant therapy.

How would that change your approach here? It sounds like more people would be willing to use oral capecitabine in this setting.

Interestingly, the patient prior to this would probably be less likely to be eligible for some of those frontline trials given that short disease-free interval. Most of these frontline trials require a disease-free interval of 12 months, and this patient might fit into that category. It was interesting to see that there were fewer people who would want to offer this patient a trial, but perhaps because there’s a suggestion that there’s some chemosensitivity given that 2-year disease-free interval, and a greater willingness to try oral capecitabine.

Does anybody have anything to add? What made you change from a clinical trial or IV single agents to oral chemotherapy?

 I don’t know if [my approach] changed, but the fact that she [responded] at first is telling me that she may have a little bit more indolent disease in spite of the visceral sites. I may get some years from single-agent paclitaxel or a month to a couple of years. I’ve had it happen to my patients. It’s well-tolerated outside of neuropathy, which can be telling me to stop.

 What would you have offered the version of this patient with earlier relapse?

 The question would be if she is eligible [for clinical trials]. It’s not that I had a particular study in mind, but I would screen [her] and make sure I don’t miss a window of enrolling her in some studies. I’m surprised by what you just said, but it’s interesting not to miss anything or not to pretreat heavily. Then the performance status would not be good enough for a clinical trial. Screen first and then offer treatment.

 That’s a great point. I agree with you. It’s frustrating that a lot of these frontline trials require a 12-month disease-free interval. Because when you think of clinical trials, it’s those early relapses that you worry the most about and want to offer novel therapy to. I share that thought process with you.

I will say we do have a trial right now of sacituzumab govitecan [Trodelvy] with or without pembrolizumab [Keytruda] in early relapses who are PD-L1 negative. There are some trials out there, looking at these early relapses. But most trials have historically required a disease-free interval of a year.

During a live virtual event, Rita Nanda, MD, discussed the choice of therapy for a patient whose metastatic triple-negative breast cancer recurred after adjuvant chemotherapy with paclitaxel. 

Part 1: Choosing Therapy for a Patient With Recurrent Metastatic TNBC 

Pedro C. Barata, MD, MSc, discusses the use of darolutamide in patients with hormone-sensitive prostate cancer.

Understanding Why Darolutamide Stands Out Among ARPIs for mHSPC

Pedro C. Barata, MD, MSc, associate professor of medicine at Case Western University and director of the Clinical Genitourinary Medical Oncology Research Program at University Hospitals Seidman Cancer Center in Cleveland, Ohio, discusses the use of darolutamide (Nubeqa) in patients with metastatic hormone-sensitive prostate cancer (mHSPC).

Darolutamide demonstrated efficacy as part of both triplet and doublet therapy for mHSPC. While ARASENS (NCT02799602) showed an overall survival (OS) benefit, ARANOTE’s (NCT04736199) shorter follow-up has not yet yielded mature OS data, though Barata anticipates such a benefit with longer observation.

Darolutamide stands out for its favorable safety profile, including minimal drug-drug interactions (DDIs), reducing risks when used with common medications. Unlike other androgen receptor pathway inhibitors (ARPIs), it rarely causes rash, thyroid dysfunction, cognitive issues, or seizures.

Barata’s real-world experience, including cases where docetaxel is omitted, suggests darolutamide plus androgen deprivation therapy (ADT) alone is effective and well-tolerated. Ongoing studies like ARASEC (NCT05059236) in the Unites States are expected to further look at darolutamide’s role in the mHSPC setting.

 In the hormone-sensitive space, we have data with a triplet therapy on ARASENS and then with doublet therapy in ARANOTE. From the efficacy perspective, it is always relevant to talk about the specific setting. From the safety perspective, I think we know now that darolutamide is known to be an ARPI with the lowest number of DDIs known. [Patients] take it twice a day, which is different from the other ARPIs available. The other perspective is it appears to be very well tolerated by patients. Of course, the more you use, the more experience you get with them. But some of the things that favor the use of darolutamide include the very low number of DDIs. You don't really worry much about rash. You don't worry much about things like checking for thyroid dysfunction or even mental fogginess, for that matter, or seizures. So there are certain characteristics of darolutamide that make it a very favorable ARPI to use in this setting.

 We use therapies based on approval, not necessarily based on merits. So, we do have ARANOTE supporting its use in the hormone-sensitive space without chemotherapy. We have not seen OS difference because the follow-up was short. In this setting, we need to wait until we have mature survival data. I think we will see it, by the way, I think we'll see that difference, but we need longer follow-up to appreciate the difference in survival…because the life expectancy for these patients is measured in several years, not measured in 2 years. So from that point of view, I think the results from efficacy point of view will be aligned. It was a study [outside of the United States]. We'll have experience in the United States with the ARASEC trial ran by Dr Shore and colleagues.

 I think that will, if I were to predict the future, I think we will have robust data with darolutamide along with ADT without docetaxel to support its use by itself. Some patients, I've done it without docetaxel. Those are the patients where initially they're being considered for triplet therapy, and for whatever reason, we end up not being able to bring docetaxel on board, and they remain on darolutamide and ADT. I have done that successfully, so in general, experience is very good. Patients do very well and it's a very good option for those patients who get to us with metastatic hormone-sensitive disease.

This approval of belzutifan (Welireg) for the treatment of advanced renal cell carcinoma (RCC) is supported by findings from the phase 3 LITESPARK-005 study (NCT04195750).

Statistically significant and clinically meaningful improvements in progression-free survival (PFS) were observed with belzutifan.

Belzutifan is now an FDA-approved treatment for adult patients with advanced renal cell carcinoma.

Omar Mian, MD, PhD

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