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

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

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

Twitter

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

Fred R. Hirsch, MD, PhD, discusses how genomic testing has expanded over the last few years and has impacted the lung cancer treatment paradigm.

Genomic Testing Expands With Evolving Lung Cancer Treatment Paradigm

Fred R. Hirsch, MD, PhD, shares a message with oncologists regarding molecular testing in patients with lung cancer. He says the most important message is that molecular characterization of the patient&rsquo;s tumor must be done in order to best treat the patient.

Expert Highlights Importance of Molecular Testing in Patients With Lung Cancer

Fred R. Hirsch, MD, PhD, Professor of Medicine and Pathology, Associate Director for International Programs, University of Colorado Cancer Center, discusses the importance of biomarkers for lung cancer.

The Importance of Biomarkers for Lung Cancer

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

A 64-year-old Asian woman presented with persistent dry cough and mild progressive dyspnea over last month, with unintentional weight loss of 8 lbs over the last 4 months​. She had a past medical history of hypertension and hypercholesterolemia​ and is a never-smoker​. Right lower lobe (RLL) auscultation revealed decreased breath sounds​. Her ECOG performance status was 1. A CT scan showed a 3.5-cm mass in RLL, small right pleural effusion with nodularity as well as mediastinal lymph nodes. ​PET/CT showed multiple bone metastases, including vertebrae and left scapula​. Brain MRI was negative for brain metastasis​. Mediastinal node endobronchial ultrasound led to diagnosis of non–small cell lung cancer (NSCLC); TTF1+ adenocarcinoma; stage IVB.

IO monotherapy or IO-IO combination therapy

So 60% of us [chose a] platinum-containing chemotherapy doublet; 20% of us said chemotherapy plus IO [immunotherapy] triplet, and 20% said other. In this case, I personally would choose platinum-containing chemotherapy doublet and I would like to hear the reasons from people who chose chemotherapy plus IO or other.

: I would say that…usually we get lucky and Guardant360 is back because of the proximity of their lab between 6 and 7 days. There are no circumstances for NSCLC where I don’t wait to see the 

 status. But if I wanted to wait, then I would pick the doublet without an IO as well. But for PD-L1 [positive disease], I get impatient.

You would wait for the EGFR and ALK testing results before adding the IO?

I would wait before starting therapy even if the patient is anxious.

This question does say that the patient is anxious, but we never said that she’s in visceral crisis or in a medical need to start therapy. Perhaps one of us who answered ‘other’ meant to just wait. That’s an option too. I also think that chemotherapy plus bevacizumab [Avastin] is not wrong. I don’t think there is harm in giving chemotherapy plus bevacizumab in a patient with unknown marker status in a setting of no brain metastasis, [with] no risk of brain bleed.

But we do want to avoid immunotherapy upfront when you don’t know the 

 mutation status, because if patients are given IO up front, and then you find out that this patient has 

 exon 19 deletion or EML4-ALK, you want to switch them to that therapy. But when you do switch, sometimes that can cause an increase in immune-related adverse events [AEs].

 Immune-related pneumonitis is well known for 

-mutated patients when they’ve been given PD-1 inhibitor up front, followed by an EGFR-TKI [tyrosine kinase inhibitor]. And for EML4-ALK, a similar thing happens, but it shows up more in the form of immune-related hepatitis for whatever reason.

In order to avoid these extra AEs, you want to try to wait until 

 results are back before you put them on IO. One might say, I don’t have to switch right away and that’s correct. You don’t have to switch right away even if the patient has 

[mutations]. If they were put on chemotherapy plus or minus IO or IO [alone] up front and it is working, then there might not be a need to switch right away. But eventually these patients are most likely going to progress, and eventually they’re going to need these TKIs. So you want to avoid exposure to PD-1 inhibitors upfront if at all possible, so that’s why I wouldn’t choose IO-containing regimens in this particular case when we don’t know that 

So are you suggesting in general, before we have the next-generation sequencing panel back, we should not start immunotherapy at all?

That is correct, and that is for the reason I just mentioned, especially for 

, if you do find mutations after you’ve already given them IO and then you put them on a TKI, it increases the risk of AEs. For example, what has been reported for 

 and pneumonitis is that the baseline pneumonitis rate with TKI is [approximately 3% to 4%].

 But that can increase up to 11% to 12% if a patient has been exposed to an immunotherapy agent prior to TKI, and it is also the reason why concurrent use is not recommended.

 Nobody should be getting immunotherapy and EGFR-TKI or ALK-TKI at the same time.

What if the patient was highly PD-L1 positive? My answer would be I would still wait and get the rest of the molecular profiling results because if the patient had an 

, I would not give an immunotherapy upfront.

That is correct. Especially with single-agent IO, their response rates are lower than the TKIs, so you do want to wait even if the PD-L1 is high.

The patient was started on chemotherapy doublet (cisplatin and pemetrexed)​. Tissue next-generation sequencing showed 

 exon 20 insertion mutation (V769_D770insASV)​. Four months after initiation of chemotherapy (with initial partial response), she reported worsening back pain and shortness of breath​. A CT scan showed disease progression​, and repeat brain MRI showed no metastases. She received amivantamab-vmjw (Rybrevant) as second-line therapy.

1. Schoenfeld AJ, Arbour KC, Rizvi H, et al. Severe immune-related adverse events are common with sequential PD-(L)1 blockade and osimertinib. 

. 2019;30(5):839-844. doi:10.1093/annonc/mdz077

2. Lin JJ, Chin E, Yeap BY, et al. Increased hepatotoxicity associated with sequential immune checkpoint inhibitor and crizotinib therapy in patients with non-small cell lung cancer. 

. 2019;14(1):135-140. doi:10.1016/j.jtho.2018.09.001

3. Tagrisso. Prescribing information. AstraZeneca; 2022. Accessed February 15, 2024. 

4. Oshima Y, Tanimoto T, Yuji K, Tojo A. EGFR-TKI-associated interstitial pneumonitis in nivolumab-treated patients with non-small cell lung cancer. 

. 2018;4(8):1112-1115. doi:10.1001/jamaoncol.2017.4526

During a Targeted Oncology™ Case-Based Roundtable™ event, Misako Nagasaka, MD, PhD, asked participants how they would approach therapy for a patient with metastatic non–small cell lung cancer when biomarker testing is not yet completed. This is the second of 2 articles based on this event.

Selection of First-Line NSCLC Therapy Influenced by Delayed Testing 

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.

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. 

Fred R. Hirsch, MD, PhD

Articles

Latest Updated Articles