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Senthil Damodaran, MD, PhD, discusses data from a phase 2 trial of futibatinib  in patients with metastatic HR-positive/HER2-negative breast cancer with FGFR1 amplifications.

Futibatinib Shows Promise in Breast Cancer With FGFR1 Gene Amplifications

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 52-year-old, postmenopausal woman had a history of grade 2, node-negative invasive ductal carcinoma (IDC).

Estrogen receptor positive (ER+) and progesterone receptor positive (PR+); HER2 immunohistochemistry (IHC) 0; Ki-67 20%​ of the right breast; 21-gene recurrence score, 27

Initial therapy included chemotherapy, radiation therapy, and 5 years of adjuvant anastrozole.

Three years after completing anastrozole​, metastatic progression was discovered, including symptomatic bone involvement (multiple vertebrae and bilateral iliac crests).

Bone marrow aspiration confirmed ER+/PR+, HER2 IHC 0, stage IV IDC.

The patient started letrozole and ribociclib (Kisqali) with denosumab (Xgeva), with good clinical response and marked improvement in her pain​.

Required 1 dose reduction to 400 mg ribociclib due to neutropenia.

Twenty months after starting therapy, routine staging scans showed new FDG-avid sclerotic and lytic bone lesions​.

She noted mild increase in lower back pain​.

Circulating tumor DNA (ctDNA) analysis confirmed an 

Fulvestrant + a different CDK 4/6 inhibitor 

 Using fulvestrant plus a different CDK4/6 inhibitor would not be an unreasonable choice if the patient didn't have an 

 mutation. Fulvestrant alone isn’t a [definite] option for a patient like this. I probably wouldn't use exemestane plus everolimus [Afinitor] here because I don't think this patient has definitively endocrine-resistant disease. Likewise, I probably wouldn't give single-agent chemotherapy. So I would agree with the participants and give elacestrant [Orserdu].

 I absolutely agree. I think elacestrant would be a preferred option.

 But there are some other circumstances where somebody doesn't have access to elacestrant. The 

 mutation would drive me towards a selective estrogen receptor degrader over an aromatase inhibitor combination. So thinking about fulvestrant is also a reasonable option, but I think elacestrant [is a recommended] option.

 The patient received ribociclib in the first-line setting—if she got palbociclib [Ibrance], would you consider, if she didn't have any sort of mutation, fulvestrant plus ribociclib based on the MAINTAIN trial [NCT02632045]?

 I think [we take into account] the MAINTAIN data.

 They are certainly compelling. I have done that very thing in patients who lack other targetable mutations, had a good run on first-line palbociclib, and just have a small amount of progression. We did see data that ribociclib plus fulvestrant was better than fulvestrant alone in that population. I would consider that, remembering that phase 2 hypothesis-generating study.

 mutation, what comes first? How do you deal with that?

 It's a very good question. It's a data-free zone, but I think given the toxicity profile, I probably would lean towards elacestrant.

 I think this depends on the patient in front of you and the volume of their disease. Are they symptomatic, and are we feeling comfortable with single-agent endocrine therapy knowing that we still have the ability to target the PIK3CA pathway at the subsequent progression? I think in the absence of data, it's an art-of-medicine decision. I think there's a place for single-agent endocrine therapy, given the constellation of risk-benefit balance.

 When you look at SOLAR-1 [NCT02437318], the benefit with alpelisib [Piqray] was pretty significant.

 We just don't know the answer right now. And I think you're absolutely right, it depends on the patient.

1. NCCN. Clinical Practice Guidelines in Oncology. Breast cancer; version 2.2024. Accessed June 6, 2024. 

2. Kalinsky K, Accordino MK, Chiuzan C, et al. Randomized phase II trial of endocrine therapy with or without ribociclib after progression on cyclin-dependent kinase 4/6 inhibition in hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer: MAINTAIN trial. 

. 2023;41(24):4004-4013. doi:10.1200/JCO.22.02392

3. André F, Ciruelos EM, Juric D, et al. Alpelisib plus fulvestrant for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: final overall survival results from SOLAR-1. 

. 2021;32(2):208-217. doi:10.1016/j.annonc.2020.11.011

During a Case-Based Roundtable® event, Ruth M. O'Regan, MD, looks at options for a patients with hormone receptor–positive, HER2-negative breast cancer and an ESR1 mutation in the second article of a 2-part series.

Second-Line Targeted Options Considered in ESR1-Mutated Breast Cancer

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?

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. 

Senthil Damodaran, MD, PhD

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