BRAIN CANCER

HER2 Breast Cancer

BREAST CANCER

Bladder Cancer

Prostate Cancer

Renal Cell Carcinoma

GENITOURINARY CANCERS

Liquid Biopsies

GENOMIC TESTING

Colorectal Cancer

GIST

Gastric Cancer

GI CANCERS

Cervical Cancer

Endometrial Cancer

Ovarian Cancer

GYNECOLOGIC CANCERS

HEAD & NECK CANCERS

Bone Marrow & Stem Cell Transplant

HEMATOLOGY

CAR T-Cell Therapy

IMMUNOTHERAPY

Chronic Lymphocytic Leukemia

Chronic Myeloid Leukemia

LEUKEMIAS

Biomarker-Driven Lung Cancer

EGFR+ Lung Cancer

MET-Targeted Therapy

Small Cell Lung Cancer

LUNG CANCER

DLBCL

Follicular Lymphoma

Mantle Cell Lymphoma

LYMPHOMAS

MPNs

MULTIPLE MYELOMA

NTRK GENE FUSIONS

SARCOMA

Melanoma

SKIN CANCERS

THYROID CANCERS

NEWS

All News

FDA Briefs

Oncology Icons

Special Reports

The Targeted Pulse

Voices from the Field

CONFERENCES

Conference Coverage

Conference Listing

Data Dialogue with the Oncology Brothers

MEDIA

All Videos

Case-Based Peer Perspectives

Expert Perspective Virtual Tumor Board

Interviews

Investigator Perspectives

Medical World News

Pivotal Practice Views with the Oncology Brothers

Podcasts

Precision Medicine

Speaking Out

PUBLICATIONS

All Publications

Evolving Paradigms

Peers & Perspectives in Oncology

Targeted Therapies in Oncology

CASE-BASED ROUNDTABLE

PARTNERS

RESOURCES

CME/CE

Clinical Trials

Events

Precision Medicine Perspectives

Press Releases

Treatment Resources

SUBSCRIBE

Targeted Oncology provides news, videos, and reviews on the rapidly evolving world of targeted therapies and immunotherapy for oncologists treating patients in a community setting.

About Us

Advertise

Contact Us

CureToday.com

CancerNetwork.com

OncLive.com

OncNursingNews.com

Do Not Sell My Information

Privacy

Terms & Conditions

Targeted Oncology - Immunotherapy, Biomarkers, and Cancer Pathways

Facebook

Linkedin

YouTube

Instagram

Featured Clinical Focus

BTK Inhibitors: In-Focus

Bone Marrow & SCT

EGFR-Positive Lung Cancer

Lung Cancer

Multiple Myeloma

Thyroid Cancers

Clinical Focus

Brain Cancer

Breast Cancer

Gastrointestinal Cancer

Genitourinary Cancers

Gynecologic Cancers

Head & Neck Cancers

Hematology

Leukemias

Lymphomas

Sarcoma

Skin Cancers

Spotlight

1rem

Authors

Dark zone lymphoma includes aggressive B-cell lymphomas with shared molecular features. While some respond to escalated treatment, others remain resistant, highlighting the need for targeted approaches to improve outcomes.

What Is Dark Zone Lymphoma, and Is It Clinically Relevant?

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 54-year-old man with a history of metastatic renal cell carcinoma (mRCC) had left nephrectomy and adrenalectomy. Four years later, he had recurrence with lung nodules with biopsy consistent with clear cell RCC. ​It was subsequently recognized that nodules had been present on scans over 2 prior years​. He was observed based on low-volume and indolency of disease and patient preference​.

Eighteen months later, there was continued indolent growth on scans, increased total tumor burden, a new paratracheal lymph node (2.0 × 1.5 cm), and multiple growing pulmonary nodules. A decision was made to initiate systemic therapy with pembrolizumab (Keytruda) plus axitinib​ (Inlyta). He had stable disease on follow up​. Moderate diarrhea (well controlled with antidiarrheal medication) and mild fatigue was reported​. After cycle 6, he developed fatigue, mild shortness of breath, and mild cough without chest pain. Pulse oximetry was 88% at rest. He had no fever, no recent sick contact, and his flu vaccine up-to-date.​Infectious workup was negative​. A chest CT at approximately week 18 confirmed grade 3 pneumonitis, and pembrolizumab was held​. Oral steroids were administered. Ultimately, pembrolizumab was discontinued, while the patient continued on axitinib​.

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 confirmed disease progression: growth of paratracheal lymph node (was 20 × 15 mm; now 25 × 28 mm), new mediastinal and hilar nodal involvement, new retroperitoneal nodes, and new lytic lesions​. His ECOG performance score was 1. ​

Single-agent VEGF-TKI (eg, axitinib, cabozantinib)

VEGF TKI combination (ie, lenvatinib + everolimus)

Immune checkpoint inhibitor regimen (eg, nivolumab ± ipilimumab)

What additional workup would you order at this point? ​

What factors affect your decision-making for second-line therapy?​

 What additional workup would you order at this point for this patient? Do we need any workup?

 I think I would consider doing an MRI with the brain as well, especially with the bony metastatic disease in the spine. That would be helpful before starting him on some form of second-line treatment, either cabozantinib [Cabometyx]—especially given his bony metastatic disease where we know that cabozantinib works very well—or everolimus (Afinitor) are good options.

 That’s a great thought. Bony metastasis, and particularly spine lesions, are often associated with brain metastases, so that’s not an unreasonable consideration even in the absence of symptoms.

 Yes, I agree. I think those are both good options. Some physicians would think about next-generation sequencing [NGS]. I don’t know if that would help at this point.

 For NGS, 1 question would be whether to use the old tissue from the lung biopsy or the nephrectomy sample, or get a new biopsy.

 If I find it would help make a decision, I would probably get a fresh biopsy. I’m just not sure it would help in the choices at this point. You can use lenvatinib [Lenvima] plus everolimus or you can use cabozantinib regardless.

 Absolutely, that’s correct. That’s a great point. In the absence of a biomarker, [what factors] help you decide—response and tolerance to the prior therapy, aggressiveness of the disease, disease burden, toxicities from the previous, for TKI [tyrosine kinase inhibitor] versus immunotherapy, mechanism of action [MOA]?

 I think that if they received prior immune checkpoint inhibitor, even if you combine it with a TKI, that the response would be less. I would choose cabozantinib as a second line, [not] another immunotherapy in the second line in this case.

 That makes perfect sense because the patient had a major immune-mediated adverse event [AE] that required systemic steroid and long course taper. Does anybody consider the MOA?

 Given that he was on axitinib when he progressed, you would want to vary the MOA a little bit, see if he can get better disease control with a new MOA, so adding an mTOR [inhibitor] or something like that might change the disease progression.

 That makes sense. Do you think there are differences between TKIs? Are all the TKIs the same?

 There definitely are differences; cabozantinib has multiple targets, especially in the 

 [mutations] are things that you want to make sure you target because with axitinib you’re only targeting the 

, targeted by lenvatinib, is known to show resistance in that pathway when patients are on prior VEGF inhibitors. So I think both choices are good.

I think age and performance status are important. With the doublet combination, you definitely want patients to have good performance status. In terms of tolerability of single-agent cabozantinib, I think we know that it works well, and it’s very well tolerated. Patient outcomes for quality of life are also reported with cabozantinib in many studies.

 Who would look at the National Comprehensive Cancer Network guidelines for selecting treatments here?

 I usually peer at them if I haven’t seen a second-line patient in a while just to make sure I didn’t miss something, to confirm it. It is important to make sure that you don’t miss a major change.

 Absolutely. It keeps on changing and there are going to some changes in the near future based on the recent data.

 [Concerning the option to use an] immune checkpoint inhibitor…it wasn’t a long time ago that he had the exposure. He didn’t have progressive disease on the first-line immunotherapy, so given the other [options] are just changing a little bit of the MOA, not a whole lot, and immunotherapy gives a totally different MOA, is it unreasonable to cautiously consider [immunotherapy]?

 The only problem is the grade 3 pneumonitis in this patient…his [pulse oximetry] was 88%. He required oxygen supplementation at that time along with a high-dose steroid. The question is, could that recur with reintroduction of nivolumab [Opdivo] or pembrolizumab? It could happen, not necessarily right away. This is [caused by] immune activation by the immune checkpoint inhibitor. The frequency of AEs have been [greater] in patients who already had an immune-mediated AE. I would definitely consider using it, but I would reserve it for later lines because when they have recurrent immune-mediated AE, there have been multiple reports that they have more than one immune-mediated AE—pneumonitis, nephritis, colitis, a lot of them come together, and renal insufficiency. It’s not unreasonable to choose something else and maybe revisit when you run out of options.

I would agree with Dr George. I think it’s a reasonable thing to consider, and I think these clinical trials now are actively looking at this. So trials like CONTACT-03 [NCT04338269] are looking at immunotherapy, post-immunotherapy, and cabozantinib plus atezolizumab [Tecentriq] versus cabozantinib after you [had] prior immunotherapy. There is 1 with tivozanib [Fotivda] as well, TiNivo-2 [NCT04987203], that is looking at this very question: can you get a response after progression on prior immunotherapy.

1. NCCN. Clinical Practice Guidelines in Oncology. Kidney cancer, version 3.2023. Accessed December 8, 2022. https://bit.ly/2TAx1m3

During a Targeted Oncology case-based roundtable event, Saby George, MD, discussed which second-line therapy would be appropriate for a patient who discontinued frontline immunotherapy/tyrosine kinase inhibitor therapy due to immune-related toxicity. 

Second-Line Considerations After Immune Toxicity From Prior RCC Therapy

The combination of selinexor (Xpovio) with ruxolitinib (Jakafi), in both 40mg and 60  mg doses, demonstrated encouraging efficacy with a manageable safety profile in patients with myelofibrosis (MF) who were previously treated with ruxolitinib, according to preliminary findings from a phase 2 trial (NCT04562389). These data were presented at the 2024 ASH Annual Meeting.

“At ASH 2023, we presented promising efficacy and safety data in the real-world setting for selinexor in combination with ruxolitinib in patients with MF. Here we will report the efficacy and safety of the regimen in patients in a prospective clinical trial who received prior treatment with ruxolitinib,” Minghui Duan, PhD, said during a presentation of the data.

Duan is affiliated with the Department of Hematology at Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College in Beijing, China.

The prospective, open-label, multicenter phase 2 study enrolled a total of 38 patients.

 By July2024, all 38 patients received at least 1 dose of selinexor, and at a 6-month analysis, 88% of patients had a reduction in spleen length and 36% achieved a spleen response, Duan stated. Spleen response was defined as a reduction in length that is more than 50% per the International Working Group-Myeloproliferative Neoplasms Research and Treatment and European LeukemiaNet response criteria.

Regarding symptom response, 30 patients were evaluable with 26 patients (86.67%) experiencing alleviation of their symptoms, 9 patients (40.91%) achieving a 50% reduction in either total symptom score (TSS) or clinical-assessed symptom response, and 1 patient (3.33%) achieved symptom resolution.

Four of the 9 patients who were transfusion-dependent achieved transfusion independence after treatment with the combination, according to Duan.

In total, there were 27 patients who received a 60 mg dose of selinexor, 10 who received a 40 mg dose, and 1 patient who received a 20 mg dose. The frequency of dose-administration was weekly across all doses.

The primary end point for the trial was spleen response. This was assessed by palpation or CT and MRI. The secondary end points were anemia response, symptom response, and safety.

The median age across all patients was 65.5 years (range, 22-84), and 17 patients (44.74%) were male. The mean duration of prior ruxolitinib treatment was 20.5 months (range, 3.6-138).

Across all 38 patients, 25 (65.79%) harbored a 

 mutation, and 2 patients (5.26%) had triple-negative MF. Data were missing for 3 patients (7.89%), and data for the remaining patients were unspecified. According to the Dynamic International Prognostic Scoring System model, 23 patients (60.53%) were classified as intermediate risk, 10 (26.32%) as high risk, and 5 (13.16%) as unknown. In addition, 36 patients (94.74%) had splenomegaly at diagnosis.

Selinexor with ruxolitinib demonstrated encouraging efficacy with a manageable safety profile in patients with myelofibrosis who were previously treated with ruxolitinib.

David W. Scott, MBChB, PhD

Articles

Latest Updated Articles