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Churilla said the majority of patients on a national level had insurance, with only 15% of patients utilizing medicaid and 5% of patients being uninsured.

Dr. Thomas Churilla on Insured Versus Uninsured Patients With Head and Neck Cancer Getting Treatment

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.

News

Clinical

FDA Accepts BLA for Subcutaneous Nivolumab Across Various Solid Tumors

Revumenib Crosses the Finish Line For KMT2A-Rearranged Acute Leukemia

Revumenib (SNDX-5613) has received FDA approval for the treatment of adult and pediatric patients with relapsed/refractory (R/R) 

-rearranged acute leukemia. This approval is based on data from the phase 1/2 AUGMENT-101 trial (NCT04065399), which evaluated the efficacy and safety of the drug in a total of 94 patients with R/R 

 acute leukemia, acute lymphoblastic leukemia (ALL)/mixed phenotype acute leukemia, and acute myeloid leukemia (AML). Minimal residual disease was also evaluated in 10 patients as part of the study.

-rearrangements occur in patients with acute myeloid and ALL, in adults, children, and overall, and have a poor prognosis. Revumenib gives hope to those with relapsed and refractory 

disease. I hope to see this agent investigated in clinical trials for newly diagnosed 

AML and ALL,” Eytan M. Stein, MD, chief of the leukemia service and director of the Program for Drug Development in Leukemia, Division of Hematologic Malignancies, at Memorial Sloan Kettering Cancer Center in New York, New York, told Targeted Oncology

Dato-DXd Moves Into Last Phase For FDA Approval in EGFR-Mutated NSCLC

A newly submitted biologics license application seeks accelerated approval of datopotamab deruxtecan (Dato-DXd) for the treatment of metastatic or locally advanced 

-mutated non–small cell lung cancer (NSCLC). This indication replaced the initial nonsquamous NSCLC application following feedback from the FDA. The submission is based on data from the following trials/phases evaluating Dato-DXd in various designs: the phase 2 and phase 3 TROPION-Lung01 (NCT04656652), TROPION-Lung05 (NCT04484142), and TROPION-PanTumor01 (NCT03401385).

“TROPION-Lung01 was designed to test the potential to improve upon standard-of-care chemotherapy in patients with a broad, previously treated, advanced lung cancer patient population. The results, together with data from TROPION-Lung05, showed an especially pronounced benefit for patients with an 

 mutation, which informed our discussions with the FDA and the decision to seek accelerated approval of datopotamab deruxtecan in this patient population. TROPION-Lung01 has also provided exciting exploratory data supporting our biomarker development, which will be validated in ongoing and planned phase 3 lung cancer trials,” Susan Galbraith, executive vice president of Oncology Research and Development at AstraZeneca, stated in the press release.

“Managing CML Is a Marathon”: Gain Insights on

Maintaining open and personalized communication with patients treated for chronic myeloid leukemia (CML) is a necessity due to the growing arsenal of (TKIs) and the time spent on treatment. Certain patients achieve an early response, but for others, treatment can be lifelong, requiring prompt management of serious adverse events, Michael Mauro, MD, explained. Mauro explores the current challenges and real-world data on CML, highlighting new TKIs that have a significant effect.

“Managing CML is a marathon requiring a minimum of 3 to 5 years of therapy even with our current best thoughts on the curative pathway, and that is only for a select group of patients. This group of patients is able to achieve an early and optimum response. [However], for the majority of patients, it is chronic or even lifelong therapy—more like an ultramarathon. Managing adherence, compliance, [and] tolerability and keeping the lines of communication open with patients is essential, as adverse events are often lower grade, though serious ones must be managed quickly,” Mauro, director of the CML program in the leukemia service at Memorial Sloan Kettering Cancer Center in New York, New York, stated in an interview with Targeted Oncology

Key Updates in TKI Therapy Reveal A Notable Challenge in CLL

A challenge in managing chronic lymphocytic leukemia (CLL) is disease progression for patients who have been treated with covalent Bruton's tyrosine kinase (BTK) inhibitors and venetoclax (Venclexta), according to Nicole Lamanna, MD. At the 42nd Annual Chemotherapy Symposium Foundation, hosted by Physicians' Education Resource, LLC, Lamanna reviewed a range of treatment options for heavily pre-treated CLL, discussing pertinent trials as well as research on the potential role of chimeric antigen receptor (CAR) T-cell therapy in CLL.

“Our patients who have relapsed multiple times are becoming a new clinically unmet need. With the covalent and the venetoclax- based therapies, patients can be bridged to a non-covalent, like ibrutinib [Imbruvica]. These patients are not going to last that long, so they need to get on a clinical trial or bridge or receive CAR T-cell therapy if they’re eligible,” Lamanna said. Lamanna is an associate clinical professor of medicine in the Hematologic Malignancies Section of the Hematology/Oncology Division at Columbia University Herbert Irving Comprehensive Cancer Center in New York, New York.

Discussing Quadruplet Therapy in Transplant-Eligible Multiple Myeloma

Marc J. Braunstein, MD, PhD, FACP, and hematology/oncology fellow and Olivia Main, MD, discussed a case involving a patient with transplant-eligible multiple myeloma. In the discussion, they highlight data from the phase 2 GRIFFIN (NCT02874742) and PERSEUS (NCT03710603) trials, explaining the efficacy of a quadruplet regimen vs a triplet regimen for this patient population.

“Those who received the quadruplet regimen had statistically significant improvement…This was also seen both at the end of the induction therapy as well as at the end of final analysis. [The percentage of] those who achieved a CR or better after the end of induction was around 19% in the D-RVd group, but we saw this even further depth of response increase at the end of the final analysis to 83% in those who received the quadruplet regimen, compared with 60% of patients who received the triplet regimen alone. This led to another study, the PERSEUS trial, which also demonstrated that the quadruplet regimen improved the depth of responses for these patients,” Main explained in the discussion with 

Thank you for joining us for this week’s 

In case you missed it, here is last week’s 

The FDA grants approval to revumenib (SNDX-5613) for a subgroup of acute leukemia, and dato-dXd moves into the final stage in NSCLC. We also cover expert updates from the 42nd Annual Chemotherapy Symposium Foundation in CLL, as well as other relevant insights on CML and multiple myeloma treatment.

The Targeted Pulse: Discover Key FDA Actions in Leukemia and NSCLC and The Significant Effects of TKIs in CML and CLL 

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.

 I agree with my colleagues. I like the idea that you can give tafasitamab for a limited period of time and then continue on lenalidomide. There’s a lot of familiarity with lenalidomide from other malignancies, and we know how to dose adjust and what to monitor for.

 Does anybody worry about giving a CD19-directed therapy with tafasitamab before giving a CD19-directed CAR T-cell therapy?

 I’ve talked to my transplant specialists and CAR T cell specialists about it…and they seem comfortable. I don’t know why, but they feel very comfortable with tafasitamab/lenalidomide prior to CAR T-cell therapy as a bridging therapy.

 That’s true. There was some concern about the CD19, but I don’t think they’re worried about it.

 There has been a continual concern about giving CD19-directed therapy before another CD19-directed therapy in either direction, giving CAR T-cell therapy before tafasitamab/lenalidomide or giving tafasitamab/lenalidomide or loncastuximab tesirine [Zylonta] before giving CAR T-cell therapy.

There have been retrospective observational studies presented at national meetings that show it can be done successfully, and that you can still get good responses from the second CD19 therapy in both directions.

 In those patients who relapse on the lenalidomide/tafasitamab combination, have they looked at what their CD19 status is?

 The studies that I’ve mentioned are all small studies and in relatively few patients that have gone on to subsequent therapy. CD19 as an antigen is tricky to look at, too, because there are multiple ways that you can have CD19 loss in terms of the ways it affects its expression. We know about CAR T-cell therapy and CAR T-cell failure and that CD19-low is one of the pathways for CAR T-cell failure in about 25% to 30% of patients.

 And there’s a concern that if you give a CD19 therapy before another CD19 therapy that you might have CD19 loss as a mechanism, but that pathway has not been studied.

: In the trial, bridging chemotherapy was forbidden. So I don’t know how one would apply those data if you’re going to use some chemotherapy, which sometimes we end up having to do if steroids don’t seem to be enough. But those are usually patients who have a very aggressive disease with high lactate dehydrogenase and so on. So what is your assessment of that, what we do in the community as opposed to what was done in the trial?

 You are correct, there are some challenges there. One is the practicality of getting a patient to CAR T-cell therapy; getting all the insurance approvals can be challenging and making sure that those are in place, so the patients can go on to therapy. There oftentimes is a need for therapy to get a patient to the CAR T cells. There are patients who can get the CAR T cells more quickly or can have just simple steroids as a therapy.

I think 1 of the things that we did have concerns about early on is that if you gave steroids, that they would inhibit the ability of CAR T cells to work. We now know that’s not true and that bridging with steroids was a reasonable and effective approach in the axicabtagene ciloleucel [Yescarta] randomized trials, the ZUMA-7 trial [NCT03391466], and in other studies.

We’ve also found from our University of Texas MD Anderson Cancer Center group led by Chelsea C. Pinnix, MD, PhD, that bridging radiation can be quite an effective therapy, particularly when the disease is in a relatively limited area.

Those are the kinds of approaches that we think about when you want to limit what’s given for bridging therapy. But, oftentimes, you do need to pursue another regimen. What I typically recommend is the use of polatuzumab without bendamustine as an off-label approach for being able to treat patients and to get them to CAR T-cell therapy [without] giving a CD19-directed therapy. But we have also seen that people get regimens like tafasitamab/lenalidomide as a bridging therapy or get a chemoimmunotherapy regimen as a bridging therapy. I think all of those are potential approaches in real life that can get people to CAR T-cell therapy.

1. Thapa B, Caimi PF, Ardeshna KM, et al. CD19 antibody-drug conjugate therapy in DLBCL does not preclude subsequent responses to CD19-directed CAR T-cell therapy. 

 2020;4(16):3850-3852. doi:10.1182/bloodadvances.2020002587

2. Caimi PF, Ardeshna KM, Reid E, et al. The antiCD19 antibody drug immunoconjugate loncastuximab achieves responses in DLBCL relapsing after antiCD19 CAR-T cell therapy. 

 2022;22(5):e335-e339. doi:10.1016/j.clml.2021.11.005

3. Jacobson CA, Hunter BD, Redd R, et al. Axicabtagene Ciloleucel in the Non-Trial Setting: Outcomes and Correlates of Response, Resistance, and Toxicity. 

 2020;38(27):3095-3106. doi:10.1200/JCO.19.02103

4. Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. 

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. 

Thomas Churilla, MD

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