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During a Targeted Oncology Case-Based Peer Perspectives event, Todd Bauer, MD, medical oncologist, Tennessee Oncology, discussed the results from clinical trials that include patients with RET-altered lung cancer to determine a treatment strategy for a 59-year-old patient.

Trial Results Show Patients With RET Alterations Experience Different Efficacy With Lung Cancer Therapies

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

The patient is a 61-year-old man, married, father of 2 grown children and 5 grandchildren who live nearby, active lifestyle (daily walks, golfs regularly)​

History of low-volume, indolent metastatic clear cell renal cell carcinoma (ccRCC), status post‒left nephrectomy and adrenalectomy​

Based on low-volume, indolent disease and patient preference: observation only​

One and a half years post-nephrectomy CT scan: ​

New paratracheal lymph node (2.0 x 1.5 cm) and more than 10 pulmonary nodules on CT​

Lung biopsy confirmed metastatic ccRCC​

Laboratory results: within normal limits​

The patient received first-line cabozantinib (Cabometyx) plus nivolumab (Opdivo).

Decrease or stabilization in metastatic lesions noted on follow-up imaging​.

He tolerated therapy well, with 1 interruption due to hypothyroidism on routine labs (treated with levothyroxine).

Fourteen months after initiation of systemic therapy, the patient reported increasing back pain, mild nausea, weight loss, and new onset of persistent rib pain​.

Imaging confirms progressive disease: growth of paratracheal lymph node (was 20 x 15 mm; now 25 x 28 mm), new mediastinal and hilar nodal involvement, new retroperitoneal nodes and new lytic osseous lesions​

Targeted Oncology: What are the other options in the frontline for patients with RCC?

In frontline therapy, you have basically 4 options. You have ipilimumab [Yervoy]/nivolumab, and you have the 3 immunotherapy/tyrosine kinase inhibitor [IO/TKI] regimens, cabozantinib/nivolumab, pembrolizumab [Keytruda]/lenvatinib [Lenvima], and pembrolizumab/axitinib [Inlyta]. Technically all 4 of them are category 1 for intermediate- and poor-risk disease. Three of them, the IO/TKI combinations, are also for favorable risk, though ipilimumab/nivolumab can be used in that space as well because there's now a good data set for that as well.

Which subsequent-line options are available for this patient?

Moving on to subsequent-line therapy, prior IO therapy, there's no preferred regimen, because we don't have super high-quality data answering the question of what's the best going head-to-head against each other. We have a few options that you can use that are recommended regimens. None of these recommended regimens include immunotherapy. Ipilimumab/nivolumab is under useful in certain situations, pembrolizumab/lenvatinib and those other IO/TKI combinations are also under useful in certain situations.

Recommended regimens with the highest quality data are axitinib, belzutifan [Welireg], tivozanib [Fotivda], and everolimus plus lenvatinib. There are some footnotes there, in the sense that belzutifan is approved following a PD-L1 inhibitor and a VEGF TKI. If you use ipilimumab/nivolumab, belzutifan would not be a recommended regimen next. With tivozanib, [the question is]: Can you get away with it after an IO/TKI, or should you be progressing on 2 different lines of therapy? We can debate the language of the FDA approval, but technically you can use it. However, most of those patients in that study were on third line or later.

What is the importance of selectivity for the VEGF receptor in RCC?

Most of these drugs we talk about are multi-TKI receptors. They're targeting other [receptors]. These drugs have gotten more selective over time. Axitinib and tivozanib are more VEGF selective. [If you want] a pill that is going to maximally punch that VEGF receptor, that's axitinib and tivozanib. Pazopanib [Votrient], cabozantinib, and lenvatinib are more multi-kinase targeted.

Is it a good option to rechallenge a patient with a VEGF TKI therapy?

When your patient cannot tolerate VEGF TKI therapy, sometimes—not always, because there's more similarities than differences—but sometimes you can get away with going to a different selective vs non-selective VEGF inhibitor and get success. So don't give up on VEGF TKI completely. Always consider how these drugs work. Where's that toxicity coming from? When you think about the toxicities, again, [there are] more similarities than differences, but there is a little bit of nuance as far as how [severe] is that hypertension toxicity profile vs the diarrhea or palmar-plantar erythrodysesthesia skin issue. You're going to get all of them with all of the regimens, but there's a little bit of differences based on this saturation of the VEGF receptor to the other targets that these pills inhibit.

When we think about the potency, cabozantinib, lenvatinib, axitinib, and tivozanib are more potent than the other drugs, and that's why we use them more frequently. We don't talk about pazopanib as much as we probably used to.

1. NCCN. Clinical Practice Guidelines in Oncology. Kidney cancer, version 3.2025. Accessed March 27, 2025. 

https://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf

2. Fogli S, Porta C, Del Re M, et al. Optimizing treatment of renal cell carcinoma with VEGFR-TKIs: a comparison of clinical pharmacology and drug-drug interactions of anti-angiogenic drugs. 

. 2020;84:101966. doi:10.1016/j.ctrv.2020.101966

During a live event, Benjamin Garmezy, MD, discussed treatment options in renal cell carcinoma including IO/TKI combinations plus VEGF selectivity.

Reviewing RCC Treatment Choices After Progression With IO/TKI

Polatuzumab vedotin ± rituximab ± bendamustine

What therapies would you consider for a patient like this? ​

Who is involved in the decision making?​

 More than half of you would think about tafasitamab [Monjuvi] plus lenalidomide [Revlimid] and then a little bit more than a third would consider the polatuzumab [Polivy] combination [with bendamustine and rituximab (Rituxan)], and some would consider a gemcitabine-based regimen.

It sounds like nearly all of you would treat this patient within the context of your practice …while waiting for cell therapy as opposed to referring for a clinical trial or [stem cell] transplant. I’d love to hear from somebody who chose the polatuzumab option. It gives you a lot of plus/minuses there. Would you add rituximab or bendamustine to this [regimen], and how would you use that combination?

 I voted for that. What I’ve seen our transplanters prefer is to do polatuzumab/rituximab without the bendamustine pending collection.

 So you base that on your prior experience with the CAR T-cell therapy group that you work with and that being their preference. What’s your experience with using that? How comfortable are you with it? How well does it work to control disease?

 It’s reasonably tolerated. It’s not clear that the bendamustine adds much besides toxicity. In my limited experience, it’s helped people and it’s gotten people to CAR T-cell therapy. It’s been OK.

 It does what you’re expecting it to do.

 Let’s go on to someone who uses a tafasitamab/lenalidomide regimen; does anyone want to comment on your experience with that?

 I’ve used tafasitamab/lenalidomide in this setting. The main reason is because I find it easy to manage in terms of adverse events. It mostly seems to be driven by the lenalidomide which we can easily dose modify, and we’re used to doing that with not just lymphoma but myeloma, etc.

 What dose of lenalidomide do you find you end up giving most of those patients?

 I feel like my patients don’t tolerate the lenalidomide as well as what I see typically in the trials. I’m often going down to 10 mg for a lot of my patients…that’s what I’ve been seeing.

 There is nothing [unusual] about your practice. Patients don’t tolerate lenalidomide at the starting dose [of 25 mg] that they’re using in most of the trials.

 I agree with Dr Arjunan. Lenalidomide is the 1 I always adjust. I’m using [closer to] 15 mg lenalidomide. Ten milligrams is even better [tolerated] but I push 15 mg.

During a Targeted Oncology case-based roundtable event, Christopher R. Flowers, MD, MS, discussed the choice of bridging therapy for a patient with relapsed/refractory diffuse large B-cell lymphoma who may receive CAR (chimeric antigen receptor) T-cell therapy. 

This is the second of 2 articles based on this event. 

Todd Bauer, MD

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