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Christina L. Roland, MD, PhD, discusses the preliminary results of neoadjuvant checkpoint blockade—nivolumab or nivolumab plus ipilimumab—in patients with surgically resectable undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma.

Neoadjuvant Blockade Demonstrates Significant Clinical Activity in UPS

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 65-year-old man presented with back pain for past 6 months and hematuria for 1 week.

Physical examination: palpable mass in epigastric and left hypochondriac region, firm and not tender

Laboratory results: hemoglobin, 11.4 g/dL; lactate dehydrogenase, 980 U/L; all others within normal limits

Chest x-ray: widened mediastinum with bilateral hilar enlargement

Ultrasound of abdomen/pelvis showed a left renal mass, 8 cm, with multiple enlarged para-aortic nodes

CT scan of chest, abdomen, and pelvis showed multiple mediastinal and hilar nodes, deposits in left lower lobe of lung, enlarged axillary nodes, and enhancing mass in left renal parenchyma with renal vein infiltration; lytic destruction of L4 and L5 vertebrae, left superior pubic ramus, and right ischium

Fine needle aspiration of renal mass and bone biopsy confirmed metastatic clear cell renal cell carcinoma (ccRCC).

There is not one right answer here, but let's say a decision was made to initiate IO [immunotherapy] plus TKI [tyrosine kinase inhibitor], whether it's for patient preference, your preference, because you were looking for a higher and quicker response rate, whatever that may be. If you chose to do IO/TKI, what first-line regimen are you most likely to choose for this patient? Is that axitinib [Inlyta] plus pembrolizumab [Keytruda], cabozantinib [Cabometyx] plus nivolumab [Opdivo], lenvatinib [Lenvima] plus pembrolizumab, or something else?

Nobody is choosing other, which I think is very appropriate, because there is no other approved IO/TKI regimen. There are others studied, but, but none approved. Since we're divided equally, can somebody tell me why they chose axitinib/pembrolizumab? There are no clearly right answers.

 I chose the one with axitinib because it's easier to use and discontinue when needed, because it's only a 3-day period in which, if they have to have procedures or [other treatments], you don't have to be off of it for a whole 2 weeks before and after. It makes it easier to utilize. That's the main reason I tend to gravitate to that regimen more than the others.

I chose cabozantinib/nivolumab. In patients who have bone metastases, there are data that support using cabozantinib as opposed to other [TKI].

 For somebody has sarcomatoid pathology, or papillary renal cell carcinoma, I would choose cabozantinib.

With bony disease, you like cabozantinib. Remember, cabozantinib in a combination, is a dose of 40 mg, not 60 mg, which is the way it's approved for single-agent use.

I chose lenvatinib primarily because in the CLEAR study [NCT02811861], the overall response rate was higher.

 I don't think that there is a right or wrong answer. I have used all 3 combinations. My experience with lenvatinib has been positive. I have seen patients who tolerate lenvatinib pretty well. It's easy to adjust the dose for adverse events. For this particular patient, I would use lenvatinib/pembrolizumab. But for older or frail patients, I usually go with axitinib/pembrolizumab for the reasons that were mentioned earlier.

When you do lenvatinib/pembrolizumab, what dose of lenvatinib do you start with?

I start with the full dose and then I adjust as needed.

I chose lenvatinib/pembrolizumab too, but I have not had success having patients stay on the full dose. I pretty much always start at 14 mg [of lenvatinib], and then I try to go down or up based on their tolerance. Most people cannot do 20 mg.

For this patient, I picked lenvatinib/pembrolizumab because of the clear cell histology, and I think it's pretty well tolerated. Also, when you involve the patient in the decision making, you can offer them the every-6-week infusion [of pembrolizumab], and that gets their attention more than monthly [nivolumab].

That's a good point. Are you using those every-6-weeks [dosing], or are you doing every 3 weeks? Or do you start out with every 3 weeks and then move to every 6 weeks?

I start at every 3 weeks, and then maybe for convenience, if things are stable, I do every 6 weeks.

Typically, with the combinations, you end up assessing them for toxicity pretty frequently. I've stayed at every 3 weeks unless the patient lives very far away and would prefer every 6 weeks schedule.

We have an oral chemotherapy navigating team, so I sometimes feel pretty comfortable that they're going to call them every week or 2 for the first cycle, so I don't always make them come in. But sometimes if they're going to be needing to come in any way for the first cycle or 2, it might not be a benefit to be [treated] every 6 weeks.

Are [any of you] getting ready to use the subcutaneous versions of nivolumab and pembrolizumab? Is that going to change anything? It's coming—

, and for pembrolizumab as well. It'll be interesting to see how that changes, or doesn't change, what people choose, and how they [can give] a much quicker injection, or potentially even at home.

 Geynisman previously reported consulting or advisory roles for Pfizer, Exelixis, AstraZeneca, Seattle Genetics/Astellas, Merck, and Bristol Myers Squibb.

1. Motzer RJ, Escudier B, Burotto M, et al. Nivolumab plus cabozantinib (N+C) vs sunitinib (S) for previously untreated advanced renal cell carcinoma (aRCC): Final follow-up results from the CheckMate 9ER trial. 

. 2025;43(suppl 5):439. doi:10.1200/JCO.2025.43.5_suppl.439

2. Motzer R, Alekseev B, Rha SY, et al. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. 

. 2021;384(14):1289-1300. doi:10.1056/NEJMoa2035716

During a live event, Daniel M. Geynisman, MD, and participants discussed their answers to a poll on which combination to use for a patient with advanced renal cell carcinoma. 

Participants Explain Rationale for Different IO/TKI Options for ccRCC

The FDA has granted full approval to larotrectinib (Vitrakvi) for patients with solid tumors harboring an 

 gene fusion without a known acquired resistance mutation.

This indication is for solid tumors that are either metastatic or located where surgical removal would likely cause significant health problems and have no adequate alternative treatment options or have continued to grow despite previous treatment.

Data from studies support this approval: LOXO-TRK-14001 (NCT02122913), SCOUT (NCT02637687), and NAVIGATE (NCT02576431).

Larotrectinib has received full FDA approval for adult and pediatric patients with solid tumors that have an 

 gene fusion without known acquired resistance, are metastatic or where surgical resection is likely to result in severe morbidity, and lack satisfactory alternative treatments or have progressed after prior therapy.

This approval is supported by data from 3 multicenter, open-label, single-arm trials: the phase 1 LOXO-TRK-14001, phase 1/2 SCOUT, and phase 2 NAVIGATE trials.

In an analysis of all 3 studies that included pediatric and adult patients with unresectable or metastatic solid tumors harboring an 

 gene fusion (n = 339), pooled efficacy results demonstrated an overall response rate (ORR) of 60% (95% CI, 55%-65%) with a complete response (CR) rate of 24% and a partial response (PR) rate of 36%. A total of 5% of patients with CRs were pathological complete responses (pCR), defined as patients with no viable tumor cells and negative margins after surgical resection and no other disease sites. The median duration of response (DOR) for these patients was 43.3 months (95% CI, 32.5 months to not evaluable).

“This first full approval of an NTRK inhibitor by the FDA represents the culmination of research and dedication by the Bayer team,” said Chandra Goda, executive director, US Vitrakvi brand lead at Bayer, in a news release. “We are proud to deliver on our promise for patients with this significant step forward, providing a treatment option for pediatric and adult patients living with 

The FDA has fully approved larotrectinib for adult and pediatric patients with solid tumors that harbor an NTRK gene fusion.

Christina L. Roland, MD, PhD

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