Perspective Therapeutics Progresses Dose Finding for [212Pb]VMT01 in Combination with Nivolumab in its Ongoing Phase 1/2a Study of MC1R-Positive Metastatic Melanoma

Rhea-AI Summary

Perspective Therapeutics (NYSE AMERICAN: CATX) announced progress in its Phase 1/2a clinical trial for [212Pb]VMT01, a targeted alpha-particle therapy for metastatic melanoma. The company has dosed the first patient with a higher dose of 3.0 mCi in combination with Bristol Myers Squibb's nivolumab (Opdivo®).

The advancement follows the Safety Monitoring Committee's review of encouraging results from previous cohorts, including five patients treated with 1.5 mCi monotherapy and two patients receiving the combination therapy at 1.5 mCi. Additionally, the company has reopened enrollment for the 3.0 mCi monotherapy cohort.

Positive

• None.

Negative

• Early stage of clinical development with limited patient data
• Efficacy data not yet reported

Insights

Oncology Clinical Trials Specialist

Perspective Therapeutics advances melanoma trial with promising safety data, increasing [212Pb]VMT01 dosage while exploring combination therapy with nivolumab.

Perspective Therapeutics has reached a significant milestone in their Phase 1/2a melanoma trial by progressing to a higher dose level of 3.0 mCi for their targeted alpha-particle therapy [212Pb]VMT01, both as monotherapy and in combination with nivolumab (Opdivo®). This advancement follows positive safety signals from earlier cohorts at the 1.5 mCi dose level.

The Safety Monitoring Committee's recommendation to escalate dosing represents a critical validation of the therapy's preliminary safety profile. In early-stage oncology trials, dose-finding is a fundamental process to establish both safety boundaries and potential efficacy signals. The reopening of the monotherapy cohort at the higher dose alongside the combination approach suggests confidence in the therapeutic window.

What's particularly noteworthy is the dual-track approach exploring both monotherapy and combination with PD-1 inhibition. This strategy allows Perspective to efficiently evaluate potential synergistic effects between targeted radiation and immunotherapy - a mechanistically sound combination as radiation can increase tumor antigen presentation and potentially enhance checkpoint inhibitor efficacy. The company appears to be methodically building evidence for contribution of effect from each treatment component, which is essential for designing future registration-directed studies.

For metastatic melanoma patients with MC1R-positive disease who have progressed on prior therapies, this represents a potential emerging option in a difficult-to-treat setting. The targeted nature of the alpha therapy could potentially offer better therapeutic ratios than conventional radiotherapies or untargeted approaches.

• First patient dosed with [²¹²Pb]VMT01 3.0 mCi in combination with nivolumab
• [²¹²Pb]VMT01 3.0 mCi single agent dose Cohort re-opened

SEATTLE, Sept. 15, 2025 (GLOBE NEWSWIRE) --  Perspective Therapeutics, Inc. ("Perspective" or the "Company") (NYSE AMERICAN: CATX), a radiopharmaceutical company that is pioneering advanced treatments for cancers throughout the body, announced today that the first patient was dosed in a new cohort of a Phase 1/2a trial evaluating the safety of [²¹²Pb]VMT01, a targeted alpha-particle therapy (TAT), in patients with previously treated, histologically confirmed metastatic melanoma and positive melanocortin 1 receptor (MC1R) imaging scans.

Patients in this cohort are receiving [²¹²Pb]VMT01 at 3.0 mCi in combination with nivolumab, a PD-1 blocking antibody developed and marketed by Bristol Myers Squibb as Opdivo®. Additionally, the [²¹²Pb]VMT01 3.0 mCi monotherapy cohort reopened for enrollment. The Safety Monitoring Committee (SMC) recommended evaluating [²¹²Pb]VMT01 at a higher dose based on its review of five patients dosed with [²¹²Pb]VMT01 1.5 mCi monotherapy and two patients dosed with [²¹²Pb]VMT01 at 1.5 mCi together with nivolumab.

"With the initiation of this second combination cohort, we are building on encouraging early safety and anti-tumor activity observed for [²¹²Pb]VMT01," commented Markus Puhlmann, Chief Medical Officer of Perspective. "Advancing to a higher dose level with [²¹²Pb]VMT01 alongside nivolumab represents an important step in evaluating the promising potential of this targeted alpha therapy in combination with immune checkpoint inhibition for patients with advanced melanoma."

"The progress of our [²¹²Pb]VMT01 program continues to reinforce our belief in its potential to transform treatment for patients with difficult-to-treat cancers," said Thijs Spoor, Chief Executive Officer of Perspective. "By moving into this next cohort, we are expanding our understanding of the therapeutic window of [²¹²Pb]VMT01 and how best to optimize efficacy and safety in a combination regimen with a PD-1 inhibitor, including contribution of effect by each component of the regimen. Through this program, we are also learning about the potential for synergy between our proprietary ²¹²Pb emitting constructs and PD-1 inhibition. Each step forward brings us closer to providing a novel treatment option for patients with limited alternatives.

About [²¹²Pb]VMT01
Perspective designed [²¹²Pb]VMT01 to target and deliver ²¹²Pb to tumor sites expressing MC1R, a protein that can be overexpressed in metastatic melanoma tumors.¹ The Company is conducting a multi-center, open-label dose escalation, dose expansion study (clinicaltrials.gov identifier NCT05655312) in patients with histologically confirmed melanoma and MC1R-positive imaging scans. In September 2024, the Company announced that the U.S. Food and Drug Administration (FDA) granted Fast Track Designation for the development of [²¹²Pb]VMT01 for the diagnosis and treatment of patients with unresectable or metastatic melanoma and who have demonstrated MC1R tumor expression. The FDA's Fast Track Designation is one of several approaches utilized by the FDA to expedite development and review of potential medicines for serious conditions and that fulfill unmet medical needs.²

About Melanoma
Melanoma is a cancer of the skin arising from uncontrollable growth of melanocytes, the melanin producing cells of the body. Metastatic melanoma is the result of melanoma that has progressed through the layers of skin, infiltrated the blood stream or lymphatic system, and traveled to other areas of the body to metastasize. In the United States, there are approximately 100,000 new diagnoses of melanoma annually and approximately 8,300 deaths annually from metastatic melanoma.³ Metastatic melanoma has a poor prognosis with limited survival of 50% at one year and 29%-35% at five years. Recent advances have led to survival improvement, but there remains a high unmet need for additional treatments, particularly for patients with metastatic disease who are refractory to front-line therapy. Median progression free survival (mPFS) for current 2L+ therapies, including lifileucel, remains limited between 2-5 months.^4,5,6

About Perspective Therapeutics, Inc.
Perspective Therapeutics, Inc. is a radiopharmaceutical development company pioneering advanced treatments for cancers throughout the body. The Company has proprietary technology that utilizes the alpha-emitting isotope ²¹²Pb to deliver powerful radiation specifically to cancer cells via specialized targeting moieties. The Company is also developing complementary imaging diagnostics that incorporate the same targeting moieties, which provides the opportunity to personalize treatment and optimize patient outcomes. This "theranostic" approach enables the ability to see the specific tumor and then treat it to potentially improve efficacy and minimize toxicity.

The Company's neuroendocrine tumor (VMT-α-NET), melanoma (VMT01), and solid tumor (PSV359) programs are in Phase 1/2a imaging and therapy trials in the U.S. The Company is growing its regional network of drug product candidate finishing facilities, enabled by its proprietary ²¹²Pb generator, to deliver patient-ready product candidates for clinical trials and commercial operations.

For more information, please visit the Company's website at www.perspectivetherapeutics.com.

Safe Harbor Statement
This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Statements in this press release that are not statements of historical fact are forward-looking statements. Words such as "may," "will," "should," "expect," "plan," "anticipate," "could," "intend," "target," "project," "estimate," "believe," "predict," "potential," or "continue" or the negative of these terms or other similar expressions are intended to identify forward-looking statements, though not all forward-looking statements contain these identifying words. Forward-looking statements in this press release include express or implied statements concerning, among other things, the Company's ability to pioneer advanced treatments for cancers throughout the body; expectations regarding the advancement of and learnings from the Company's clinical development programs, including [²¹²Pb]VMT01 as monotherapy and in combination with immune checkpoint inhibitors in different dosing cohorts; expectations regarding the potential benefits conferred by the Fast Track Designation of [²¹²Pb]VMT01, which was based on non-clinical results submitted by the Company; expectations regarding the safety profile and efficacy of [²¹²Pb]VMT01 in combination with immune checkpoint inhibitors and the potential of such treatment to transform treatment for patients with difficult-to-treat cancers; the versatility of the Company's alpha-emitter platform and its ability to enable the development of potential new cancer therapies and the exploration of combinations with established treatments; the ability of the Company's proprietary technology that utilizes the alpha-emitting isotope ²¹²Pb to deliver powerful radiation specifically to cancer cells via specialized targeting moieties; the opportunity to personalize treatment and optimize patient outcomes using the Company's complementary imaging diagnostics that incorporate the same targeting moieties; the Company's belief that its "theranostic" approach enables the ability to see specific tumors and then treat them to potentially improve efficacy and minimize toxicity; the Company's ability to grow its regional network of drug product candidate finishing facilities, enabled by its proprietary ²¹²Pb generator, to deliver patient-ready product candidates for clinical trials and commercial operations; the Company's expectations, beliefs, intentions, and strategies regarding the future; and other statements that are not historical fact.

The Company may not actually achieve the plans, intentions, or expectations disclosed in the forward-looking statements, and you should not place undue reliance on the forward-looking statements. These forward-looking statements involve risks and uncertainties that could cause the Company's actual results to differ materially from the results described in or implied by the forward-looking statements. Certain factors that may cause the Company's actual results to differ materially from those expressed or implied in the forward-looking statements in this press release are described under the heading "Risk Factors" in the Company's most recent Annual Report on Form 10-K and Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (the "SEC"), in the Company's other filings with the SEC, and in the Company's future reports to be filed with the SEC and available at www.sec.gov. Forward-looking statements contained in this news release are made as of this date. Unless required to do so by law, we undertake no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise.

Media and Investor Relations Contacts:

Perspective Therapeutics IR:
Annie J Cheng, CFA
ir@perspectivetherapeutics.com

Russo Partners, LLC
Nic Johnson
PerspectiveIR@russopr.com

¹Su DG, Djureinovic D, Schoenfeld D, et al. Melanocortin-1 Receptor Expression as a Marker of Progression in Melanoma. JCO Precis Oncol. 2024;8:e2300702. doi:10.1200/PO.23.00702.

²Guidance for Industry Expedited Programs for Serious Conditions - Drugs and Biologics. https://www.fda.gov/media/86377/download?attachment. Accessed March 5, 2025.

³Cancer Stat Facts: Melanoma of the Skin. https://seer.cancer.gov/statfacts/html/melan.html. Accessed March 5, 2025.

⁴Ascierto PA, Lipson EJ, Dummer R, et al. Nivolumab and Relatlimab in Patients With Advanced Melanoma That Had Progressed on Anti-Programmed Death-1/Programmed Death Ligand 1 Therapy: Results From the Phase I/IIa RELATIVITY-020 Trial. J Clin Oncol. 2023;41(15):2724-2735. doi:10.1200/JCO.22.02072

⁵Arance A, de la Cruz-Merino L, Petrella TM, et al. Phase II LEAP-004 Study of Lenvatinib Plus Pembrolizumab for Melanoma With Confirmed Progression on a Programmed Cell Death Protein-1 or Programmed Death Ligand 1 Inhibitor Given as Monotherapy or in Combination [published correction appears in J Clin Oncol. 2023 May 1;41(13):2454. doi: 10.1200/JCO.23.00439]. J Clin Oncol. 2023;41(1):75-85. doi:10.1200/JCO.22.00221

⁶Chesney J, Lewis KD, Kluger H, et al. Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study. J Immunother Cancer. 2022;10(12):e005755. doi:10.1136/jitc-2022-005755

FAQ

What is the current status of Perspective Therapeutics' (CATX) Phase 1/2a melanoma trial?

The trial has advanced to dosing patients with 3.0 mCi of [212Pb]VMT01 in combination with nivolumab, and has reopened the 3.0 mCi monotherapy cohort following positive safety data from lower dose cohorts.

What is [212Pb]VMT01 and how does it work?

[212Pb]VMT01 is a targeted alpha-particle therapy (TAT) designed to treat metastatic melanoma patients with positive melanocortin 1 receptor (MC1R) imaging scans.

How many patients have been treated in CATX's melanoma trial so far?

Prior to the dose escalation, seven patients were treated: five with 1.5 mCi monotherapy and two with 1.5 mCi plus nivolumab combination therapy.

What are the next steps for Perspective Therapeutics' melanoma treatment program?

The company is currently evaluating higher doses (3.0 mCi) both as monotherapy and in combination with nivolumab to optimize efficacy and safety, while studying potential synergy between [212Pb]VMT01 and PD-1 inhibition.

Who is collaborating with Perspective Therapeutics on this clinical trial?

The trial combines Perspective's [212Pb]VMT01 with Bristol Myers Squibb's Opdivo® (nivolumab), a PD-1 blocking antibody.