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Immunotherapy is the only alternative to chemotherapy and radiation for the treatment of advanced-stage tumors and recent research has shown a correlation between weight and the toxicity of these immunotherapies.

Weight May Affect Toxicity of Immunotherapies

In malignancies with limited response rates to existing radiation and/or chemotherapy, immunotherapy is being investigated as a potential adjunct, with promising results, particularly in the treatment of malignant mesothelioma.

Immunotherapy Potential Option in Mesothelioma Treatment

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

CLL Treatment Advances and Frontline Therapy Insights With Dr. Khan

Cyrus M. Khan, MD, hematologist in the Division of Hematology and Cellular Therapy at West Penn Hospital of Allegheny Health Network, discusses how treatment paradigms for chronic lymphocytic leukemia (CLL) have changed in recent years, particularly regarding frontline therapy options.

Over the last 10 years, we have seen significant changes. In the past, for younger, fit patients, we typically chose chemotherapy—most commonly the FCR regimen, a combination of fludarabine, cyclophosphamide, and rituximab [Rituxan]. However, due to its toxicity, we were always looking for alternatives. For older patients, we used bendamustine with rituximab [Rituxan], or for even older patients, single-agent chlorambucil—all chemotherapies but generally less effective than targeted treatments. Any chemotherapy, of course, comes with [adverse] effects and can increase the long-term risk of secondary cancers.

Now, we have transitioned to being entirely chemotherapy free. Most of our frontline treatments are nonchemotherapy drugs, with 2 major options. One option is starting with a BTK inhibitor; any of the options I mentioned previously, such as acalabrutinib, ibrutinib, or zanubrutinib [Brukinsa], can be used, although second-generation inhibitors like acalabrutinib [Calquence] and zanubrutinib are often preferred over first-generation ones. These treatments are very effective, but patients do need to continue them for life, as they cannot be stopped until the disease progresses. Acalabrutinib can also be combined with immunotherapy, specifically obinutuzumab [Gazyva], an anti-CD20 antibody similar to rituximab but a newer version. When combined, the [intravenous (IV)] therapy lasts 6 months while the acalabrutinib continues.

 The other major option is a BCL-2 inhibitor, specifically venetoclax, which we also combine with obinutuzumab. Here, the IV therapy continues for 6 months, and venetoclax is given for only 1 year. This regimen is an effective immunotherapy and targeted treatment combination with a defined treatment duration, so it does not have to be lifelong.

There are pros and cons to both of these options, and both are excellent choices. Physicians work closely with patients to determine the best treatment for each [patient]. Additionally, there are ongoing combination trials that investigate using BTK inhibitors with venetoclax, with or without immunotherapy, in time-limited regimens. This approach could shape how frontline treatment evolves in the future.

Cyrus M. Khan, MD, discusses how treatment paradigms for chronic lymphocytic leukemia have changed in recent years, particularly regarding frontline therapy options.

The FDA has granted Regenerative Medicine Advanced Therapy (RMAT) designation to NXC-201 for the treatment of relapsed or refractory light chain (AL) amyloidosis.

NXC-201 is a B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR) T-cell therapy.

A phase 1b/2 trial titled NEXICART-2 (NCT06097832)is currently enrolling

40 patients to further evaluate the efficacy and safety of NXC-201.

The FDA has granted RMAT designation to NXC-201, a BCMA-targeted CAR T-cell therapy, for the treatment of patients with relapsed or refractory AL amyloidosis.

NXC-201 is currently under investigation for the treatment of patients with AL amyloidosis in the phase 1b/2 NEXICART-2 clinical trial. Approximately 40 patients in total are expected to be enrolled in the trial, which is taking place at study sites in California, Michigan, New York, and Ohio.

Early findings from the NEXICART-2 study have shown promise.

 As of November 2024, 4 patients enrolled in the study had normalized their disease markers within 30 days of receiving NXC-201. Two patients achieved complete responses (CR), and the other 2 achieved minimal residual disease negativity at the 10

For safety, hematologic toxicities, including anemia, neutropenia, thrombocytopenia, and lymphopenia, were observed, consistent with expected CAR T-cell therapy adverse events (AEs). Cytokine release syndrome (CRS) occurred in a subset of patients, with grade 1 and 2 cases being the most common, though 3 patients experienced grade 3 CRS. The median time to CRS onset was one day, and the median duration was 2 days.

Additionally, organ toxicities were reported, with 3 patients experiencing congestive heart failure, four developing acute kidney injury, and 6 showing signs of hepatic injury. Infections were another concern, as 5 patients developed febrile neutropenia, and a total of 16 patients experienced infections, either early or late post-infusion.

“Receipt of FDA RMAT designation underscores the strength of our NXC-201 data and the potential for NXC-201 to provide a new treatment option for patients with relapsed/refractory AL amyloidosis, where no drugs are FDA approved today,” said Ilya Rachman, MD, PhD, chief executive officer of Immix Biopharma, in a press release.

These findings build on data from the international, 

(NCT04720313). Here, experts investigated the efficacy and safety of NXC-201 in this patient population.

 Among the 16 evaluable patients, the therapy achieved an impressive overall hematologic response rate of 94%, with 75% of patients achieving a CR.

In the NEXICART-1 trial, 13 of the 16 patients received the target dose of 800 x 10

 CAR T cells, with the remaining patients receiving lower doses.

 The median age of those enrolled was 64 years, and the majority had advanced organ involvement, with the heart (81%), kidneys (69%), and peripheral nervous system (38%) being the most affected organs. Patients received a median of 4 prior lines of therapy, with 88% being refractory to triple-drug regimens including proteasome inhibitors, immunomodulatory agents, and anti-CD38 monoclonal antibodies.

Additional data from the NEXICART-1 trial showed that 62% of patients achieved an organ response. The median duration of response was 8 months, with event-free survival (EFS) and overall survival still being analyzed at the median follow-up of 8.4 months. While the EFS was reported at 9.6 months, further follow-up is needed to fully assess long-term outcomes.

“We are also pleased to report that the pace of enrollment in NEXICART-2 has accelerated, following successful completion of the safety run-in segment. We look forward to sharing further information on our progress, including an update on NEXICART-2, in the first half of 2025,” said Gabriel Morris, chief financial officer of Immix Biopharma, in the press release.

The phase 1b/2 NEXICART-2 study is currently expanding and focusing on patients with preserved heart function who have not previously received BCMA-targeted therapy. The study will continue to evaluate the safety and efficacy of NXC-201 in a larger cohort and will assess primary end points of CR rate and overall response rate.

Early enrollment data from this trial suggests a potential for the therapy in this patient population, and the pace of enrollment has accelerated following the completion of the safety run-in segment.

As the company continues to advance NXC-201’s clinical development, further updates on the progress of NEXICART-2 are expected in the first half of 2025.

Immix Biopharma receives FDA regenerative medicine advanced therapy (RMAT) designation for NXC-201, sterically-optimized CAR-T for relapsed/refractory AL amyloidosis. News release. Immix Biopharma, Inc. February 10, 2025. Accessed February 17, 2025. https://tinyurl.com/3bky6wyw

Immix Biopharma announces positive US clinical data from first four patients in NEXICART-2 US trial of sterically-optimized CAR-T NXC-201 in relapsed/refractory light chain (AL) amyloidosis. New release. Immix Biopharma, Inc. December 19, 2024. Accessed February 17, 2025. https://tinyurl.com/2cn53kmm

Lebel E, Asherie N, Kfir-Erenfeld S, et al. Efficacy and safety of anti–B-cell maturation antigen chimeric antigen receptor T-cell for the treatment of relapsed and refractory AL amyloidosis. 

. Published online December 9, 2024. doi:10.1200/JCO-24-02252

The FDA granted Regenerative Medicine Advanced Therapy designation to NXC-201 for the treatment of relapsed/refractory light chain amyloidosis.

NXC-201 Earns FDA RMAT Designation in AL Amyloidosis

Final results from the phase 3 COSMIC-313 trial (NCT03937219), presented at the 2025 ASCO Genitourinary Cancer Symposium, showed that first-line cabozantinib (Cabometyx) combined with nivolumab (Opdivo) and ipilimumab (Yervoy) sustained a progression-free survival (PFS) benefit at 45 months of follow-up compared with placebo plus nivolumab and ipilimumab in patients with advanced renal cell carcinoma (RCC).

The updated PFS in the intent-to-treat population was 16.6 months (95% CI, 14.0-22.6) in the combination arm and 11.2 months (95% CI, 9.3-14.0) in the placebo arm (HR, 0.82; 95% CI, 0.69-0.98). The overall survival (OS) was 41.9 months (95% CI, 34.8-47.9) in the cabozantinib arm and 42.0 months (95% CI, 34.9-53.1) in the placebo arm (HR, 1.02; 95% CI, 0.85-1.23; 

Based on the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC), the PFS for those in the intermediate risk group was 22.1 months (95% CI, 14.1-25.3) in the cabozantinib arm and 11.3 months (95% CI, 8.3-16.7) in the placebo arm (HR, 0.76; 95% CI, 0.62-0.93); and for those in the poor risk group, results were 9.5 months (95% CI, 8.2-15.8) vs 11.2 (95% CI, 6.0-21.6), respectively (HR, 1.04; 95% CI, 0.73-1.48). The OS in the intermediate group was 47.9 months (95% CI, 42.6-51.6) in the cabozantinib arm vs 48.0 months (95% CI, 42.0-not estimable [NE]) in the placebo arm (HR, 0.99; 95% CI, 0.79-1.24); and for the poor risk group it was 19.4 months (95% CI, 15.8-29.3) vs 24.0 months (95% CI, 16.3-30.9) between both arms, respectively, (HR, 1.09; 95% CI, 0.78-1.51).

“There were no significant differences in OS between the 2 arms in the ITT population or by IMDC risk group,” Laurence Albiges, MD, PhD, head of the Department of Oncology at Gustave Roussy in France, said during the presentation.

Overall, 428 patients were enrolled in the cabozantinib arm and 427 were enrolled in the placebo arm. Cabozantinib was given at 40 mg by mouth daily plus 3 mg/kg of intravenous nivolumab every 3 weeks for 4 cycles and 1 mg/kg of ipilimumab intravenously every 3 weeks for 4 cycles. Patients could then transition to maintenance cabozantinib at 40 mg by mouth each day plus 480 mg of intravenous nivolumab every 4 weeks. In the placebo arm, patients were given matched treatment.

The primary end point was PFS per RECIST v1.1 per blinded independent review committee after the 249th event in the first 550 randomized patients. The secondary end point was OS after 433 events in all randomized patients.

Cabozantinib plus nivolumab and ipilimumab maintained a progression-free survival benefit at 45 months vs placebo in advanced kidney cancer.



Shadia Alam, MD

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