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When providing telehealth, providers must check individual state laws and policies regarding telehealth and providing telehealth across state lines. In sum, there is a lot to stay on top of in relation to telehealth.

Key Telehealth Factors to Monitor

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

Please discuss your answer to the polling question.

 Very interesting, 22% said mobocertinib [Exkivity] and 78% said amivantamab [Rybrevant]. Both of these answers are correct. Mobocertinib is an EGFR/HER2 exon 20 TKI [tyrosine kinase inhibitor]. Amivantamab is an EGFR c-MET bispecific antibody.

 [I chose] mobocertinib. It’s an oral medication. I know how to manage it. I’ve always done it that way. Patients will need both these agents in their lifetime. Neither of these drugs have very prolonged duration of response. I’m used to mobocertinib followed by amivantamab, and also giving patients a break from intravenous [IV] therapies. There’s no head-to-head comparison between the 2. I’ve gotten very comfortable with managing the adverse events of mobocertinib. And neither of them has CNS [central nervous system] penetration.

 I chose amivantamab because we know [for the] 2 medications, the overall response is similar, around 40%, and PFS [progression-free survival] is also similar….

 I use amivantamab; you just have to be careful…[due to] infusion reactions.

 They’re both reasonable to use. It’s a matter of oral versus IV. I haven’t used either of them. I just chose amivantamab. I thought it had a higher objective response rate [ORR], but I don’t have experience with it.

 I chose amivantamab. I haven’t used either. As others have mentioned, at least the studies show slightly higher [ORR by blinded independent review though] you can’t compare 1 [study] versus the other. [There are also] adherence issues [for IV versus oral]. I would prefer knowing when my patient is getting certain drugs.

What is your reaction to the data for amivantamab in the phase 1 CHRYSALIS study (NCT02609776)?

What’s your reaction to the CHRYSALIS data, and what stood out to you in terms of efficacy and safety?

 The disease control rate [of 74%] was amazing as demonstrated by the waterfall plot.

 The median overall survival [of 22.8 months], [though] immature for this group of patients in the second line…was extremely inspiring.

 Whenever you review a toxicity profile, you have to review it in the context of what else you have available. Patients don’t have a lot of options. They don’t respond well to chemotherapy [or] typical EGFR therapy. [Considering] the efficacy, the toxicities are manageable. You have infusion reactions so you have to watch these patients carefully, but these are not things that would dissuade me from using this drug.

 It’s a good performance for a second-line agent, giving us quite a bit of median PFS and a good response giving our patients months and maybe a year or so more disease control and ability to prolong their lives.

What is your reaction to the data for mobocertinib in the phase 1/2 trial (NCT02716116)?

What’s your reaction to these data? I’ll start with Dr Seetharamu, because you said you use this in clinical practice.

 I’m quite happy with the responses. As [for] toxicity, once you start using these agents, you get into the practice of educating patients and proactively starting antidiarrheal medications. Skin and GI [gastrointestinal] toxicity are foremost, and I proactively start managing these patients’ toxicities. Most of my patients take loperamide [Imodium] every morning, regardless of whether they have diarrhea or not. I found that extremely helpful. [I use] dose management, escalating up in some patients, especially [those] with poor performance status or who are fragile. [This is also helpful for] patients who have had prior cutaneous or GI toxicity with other TKIs [such as] osimertinib [Tagrisso] that they might have used in the past. With these strategies, I’ve been able to manage patients’ toxicities for a longer time.

 That’s a great point on dose reduction. [Although] 160 mg is the standard dose, dose reduction to 120 mg is very common and was commonly done on the study.

 We don’t have clear durability [data] at that dose, but I do think it’s important to dose reduce patients who are having toxicity.

 To me, both of these drugs are good options. I personally haven’t used [either] of them, so if I would have a chance, I would discuss toxicities with the patient. There is a slightly different toxicity profile. I don’t see a lot of difference in efficacy. They are both are good drugs and [I would] see…whether they like to come in for infusion [for amivantamab] versus having severe diarrhea and rash [with oral mobocertinib].

 I agree. It comes down to a discussion with your patient. Just because a therapy is oral does not mean that it’s easier. I have started patients on mobocertinib in the frontline setting. You do have to manage them closely [for diarrhea] and monitor [electrolytes]. They need IV hydration. You need dose holds.

Similarly, I’ve started patients on amivantamab upfront. You have to monitor for the infusion-related reaction. You have to talk to patients about the weekly infusions for the first 4 or 5 weeks, followed by [every 2 weeks]. It is a discussion with patients on managing their expectations.

 [For] mobocertinib, in the patients’ selection criteria, a good proportion of them had CNS/brain metastases. Did the study for amivantamab also treat patients with brain metastases? I wonder if that could also be a point to consider.

 For the mobocertinib study, about 35% had prior treated brain metastases.

 In amivantamab, I believe the number was 25% who had prior treated brain metastases.

 No patients went on either of these studies with active, untreated brain metastases. Neither amivantamab or mobocertinib, to my knowledge, have good CNS penetration. If you do have a patient in the second-line setting with brain metastases, there are active agents being studied, BLU-451 and ORIC-114, that preclinically do have CNS penetration. CLN-081 potentially has CNS penetration. But if you’re going to use amivantamab or mobocertinib, consider radiation of the brain metastases up front.

 If they get radiation [therapy], one is a bispecific antibody, and one is a targeted agent. Would the reaction be different with the CNS toxicity?

 We don’t see CNS toxicity with either one of these agents. For GammaKnife stereotactic radiosurgery, these are 1-day procedures. We don’t see much complication. For whole-brain radiation, you may want to hold both the TKI or the bispecific because of other systemic adverse events or symptoms patients are going to have. But we moved away from whole-brain radiation, particularly in this patient population. I have no concern giving either the bispecific amivantamab or the TKI mobocertinib in a patient who’s undergoing radiation or post radiation to the brain. The key teaching point here is: don’t allow patients to go on these agents with active, untreated CNS disease. These drugs do not have good CNS penetration.

1. Park K, Haura EB, Leighl NB, et al. Amivantamab in EGFR exon 20 insertion-mutated non-small-cell lung cancer progressing on platinum chemotherapy: initial results from the CHRYSALIS phase I study. 

. 2021;39(30):3391-3402. doi:10.1200/JCO.21.00662

2. Zhou C, Ramalingam SS, Kim TM, et al. Treatment outcomes and safety of mobocertinib in platinum-pretreated patients with EGFR exon 20 insertion-positive metastatic non-small cell lung cancer: a phase 1/2 open-label nonrandomized clinical trial.

. 2021;7(12):e214761. doi:10.1001/jamaoncol.2021.4761

During a Targeted Oncology™ Case-Based Roundtable™ event, Joshua K. Sabari, MD, discussed with participants how they would use the FDA-approved therapies amivantamab and mobocertinib for patients with non–small cell lung cancer and an EGFR exon 20 insertion alteration. 

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

Areas of Concern in Using Amivantamab and Mobocertinib in EGFR Exon 20+ NSCLC

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​

At 1.5 years post-nephrectomy CT scan: ​

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

Lung biopsy confirmed metastatic ccRCC​.

Laboratory results: within normal limits​

Approximately what proportion of your patients with metastatic RCC are like this one with favorable risk?

How often do you see cases like this? Is this the [usual type of patient] coming into your referral base, or are they more [severe] type cases? What’s typical for you in your practice?

I would say about 25% of patients are like this; 75% are more aggressive.

I think that's fair. It's nice to see that in the community. In registries we've done, it's been somewhat less than that and I do worry if things are changing. It seems to me like I see more aggressive cases. Maybe that’s because [oncologists] are so good at managing these patients with favorable risk in the community setting, they don't come to us anymore.

I see more of these type of cases. I run the thoracic program at Cone Health Cancer Center, so most of these present as lung nodule and mediastinal lymphadenopathy. Initially, it could be lung cancer, and they tend to have metastatic renal cell carcinoma. These are the ones that I keep most of the time because I was the only medical oncologist there, so I try to handle it as much as I can.

During a Case-Based Roundtable® event, Daniel J. George, MD, discusses how often community oncology participants see patients with favorable-risk vs intermediate- or high-risk RCC, and how it changes their treatment options.

Rachel V. Rose, JD, MBA

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