Phase 1b/2 "RAINIER" Frontline Acute Myeloid Leukemia (AML) Trial Initiated

Rhea-AI Summary

Aptevo Therapeutics (NASDAQ:APVO) has initiated the Phase 1b/2 'RAINIER' trial for its lead candidate mipletamig (formerly APVO436) in combination with venetoclax and azacitidine for frontline acute myeloid leukemia (AML) patients. The study aims to identify the recommended Phase 2 dose and evaluate safety, tolerability, and efficacy. Previous trials showed promising results, including a 75% complete response rate among frontline patients and efficacy outcomes more than double the benchmarks. The multi-center, open-label dose-finding study will enroll up to 39 patients across five dose levels. Primary endpoints include safety assessment, determining the maximum tolerated dose, and evaluating cytokine release syndrome incidence.

Positive

• Initiation of Phase 1b/2 'RAINIER' trial for mipletamig in frontline AML
• Previous trials showed 75% complete response rate in frontline patients
• Efficacy outcomes more than double the reported benchmarks
• 91% clinical benefit rate in combination therapy for venetoclax naïve patients
• Clinically meaningful duration of remission with no median reached

Negative

• 27% of patients experienced cytokine release syndrome in previous trials

Insights

Medical Research Analyst

The initiation of the Phase 1b/2 RAINIER trial for mipletamig (APVO436) in frontline AML is a significant development. This study aims to optimize dosing and further evaluate the drug's efficacy in combination with standard-of-care venetoclax and azacitidine. Key points:

• The trial will enroll up to 39 patients across five dose levels (9-140 mcg)
• Primary endpoints focus on safety, tolerability and determining the recommended Phase 2 dose
• Previous data showed promising results: 75% complete response rate in frontline patients and 91% clinical benefit rate in combination therapy
• Low incidence of cytokine release syndrome (27%) compared to competitors

If successful, this trial could position mipletamig as a potential game-changer in AML treatment, particularly for patients ineligible for intensive chemotherapy.

Oncology Doctor

The RAINIER trial for mipletamig in frontline AML is an exciting development in leukemia treatment. The combination of mipletamig with venetoclax and azacitidine could potentially address unmet needs in AML therapy. Notable aspects include:

• Focus on patients ineligible for intensive induction chemotherapy, a challenging-to-treat population
• Previous 75% complete response rate in frontline patients is remarkably high for AML
• The 91% clinical benefit rate in venetoclax-naive patients exceeds benchmarks, suggesting potential superiority over current standards
• Lower incidence of cytokine release syndrome (27%) could translate to better tolerability and safety profile

If these results are replicated in the RAINIER trial, it could lead to a paradigm shift in frontline AML treatment, potentially improving outcomes for this difficult-to-treat malignancy.

Financial Analyst

The initiation of the RAINIER trial for mipletamig (APVO436) is a positive development for Aptevo Therapeutics (NASDAQ:APVO). Key financial implications:

• Potential market expansion: Targeting frontline AML patients ineligible for intensive chemotherapy addresses a significant unmet need
• Competitive advantage: Previous data showing efficacy outcomes more than double the benchmarks could lead to market leadership if confirmed
• Risk mitigation: Prior safety data and low incidence of cytokine release syndrome may reduce clinical trial risks
• Partnership potential: Strong results could attract big pharma interest for licensing or acquisition
• Long-term value: Success could position Aptevo as a key player in the lucrative oncology market

However, investors should note that clinical trial outcomes remain uncertain and the company may require additional funding to complete development. Overall, this news represents a significant milestone in Aptevo's pipeline progression.

Aptevo's lead candidate APVO436 (mipletamig) to be evaluated in combination with standard of care venetoclax and azacitidine

Company anticipates new data set to bolster existing compelling data reported to date, including efficacy outcomes more than double the benchmarks*

Outcomes also expected to identify recommended Phase 2 dose

APVO436 renamed as mipletamig: Aptevo adopts new generic name for future use

SEATTLE, WA / ACCESSWIRE / August 13, 2024 / Aptevo Therapeutics ("Aptevo") (NASDAQ:APVO), a clinical-stage biotechnology company focused on developing novel immune-oncology therapeutics based on its proprietary ADAPTIR™ and ADAPTIR-FLEX™ platform technologies, today, announced initiation of the Company's Phase 1b/2 dose optimization trial, "RAINIER," as part of its ongoing program to evaluate APVO436 in combination with venetoclax + azacitidine for frontline patients with acute myeloid leukemia (AML). RAINIER will be conducted in two parts. First, a Phase 1b frontline AML study followed by a Phase 2 study. The Company also announced that APVO436 has received its generic name, mipletamig (mih-ple'-tah-mig) and will refer to its lead candidate by this name moving forward.

"With a strong foundation of positive clinical data demonstrating safety, tolerability, efficacy, and durability, we are thrilled to announce the initiation of our Phase 1b/2 RAINIER study. This trial aims to identify the recommended Phase 2 dose and further evaluate key indicators-such as safety, tolerability, and efficacy-of mipletamig when combined with standard of care venetoclax and azacitidine in frontline AML patients," stated Marvin White, President and CEO of Aptevo. "Mipletamig has already been administered to 90 patients across two trials, both as a monotherapy and in combination therapy, with results showing an exceptional safety profile and efficacy outcomes more than double those reported in the literature and a 75% complete response rate among frontline patients. We believe the RAINIER trial will not only confirm these earlier outcomes but also establish the recommended Phase 2 dose and further demonstrate mipletamig's potential to transform AML treatment when used alongside the existing standard of care."

This frontline AML study is a multi-center, multi-cohort, open label dose finding study of up to 39 patients across five dose levels ranging from 9 mcg - 140 mcg in combination with venetoclax and azacitidine (ven/aza). Subjects will be adults aged 18 or older, newly diagnosed with AML who are not eligible for intensive induction chemotherapy. Phase 1b consists of 28-day cycles of treatment in five sequential cohorts. Aptevo has partnered with Prometrika (https://www.prometrika.com/), a premier contract research organization, for the RAINIER trial.

Primary endpoints:

• Evaluate the safety, tolerability, and maximum tolerated dose (MTD) of increasing doses of APVO436 in combination with venetoclax and azacitidine in patients with newly diagnosed AML

• Determine the recommended Phase 2 dose

• Assess incidence of cytokine release syndrome (CRS) at each dose level

*Benchmark Composite References: Aldoss 2019, Maiti 2021, Morsia 2020, Garciaz 2022, Feld 2021

Secondary Endpoint:

• Determine the efficacy of increasing doses of APVO436 in combination with venetoclax and azacitidine in patients with newly diagnosed AML

"The initiation of our RAINIER trial marks a critical milestone in the clinical development of our lead candidate, mipletamig, in combination therapy for frontline AML," said Dirk Huebner, MD, Chief Medical Officer at Aptevo. "In this dose optimization trial, we will administer a combination of venetoclax, azacitidine, and mipletamig across up to five different dose levels. Our primary objective is to identify the optimal Phase 2 dose while continuing to assess the safety, tolerability, efficacy, and durability of remission. By focusing on frontline patients with this combination therapy, we aim to gain deeper insights into the role of mipletamig within the triplet regimen and its potential to improve treatment outcomes."

Prior Outcomes: Compelling Results to Date

Dose Escalation (monotherapy)

• 2 complete remissions (CRs) reported in AML patients who received the drug as a monotherapy

• Most CRS cases were low-grade and clinically manageable

Dose Expansion (combination therapy)

• 91% clinical benefit rate in combination with standard of care venetoclax + azacitidine in venetoclax naïve patients which exceeds our benchmark (Benchmark Composite References: Aldoss 2019, Maiti 2021, Morsia 2020, Garciaz 2022, Feld 2021)

  • 75% of frontline patients experienced a CR

• Clinically meaningful duration of remission, with no median reached - multiple patients either stayed on treatment or moved to transplant

• Only 27% of patients experienced CRS (cytokine release syndrome), which is favorable compared to competitor drugs.

• Most CRS cases were low-grade and clinically manageable

About Mipletamig

Aptevo's wholly owned lead proprietary drug candidate, mipletamig, targeting AML, MDS and other leukemias, is differentiated by design to redirect the immune system of the patient to destroy leukemic cells and leukemic stem cells expressing the target antigen CD123, which is a compelling target for AML due to its overexpression on leukemic stem cells and AML blasts. This antibody-like recombinant protein therapeutic is designed to engage both leukemic cells and T cells of the immune system and bring them closely together to trigger the destruction of leukemic cells. Mipletamig is purposefully designed to reduce the likelihood and severity of CRS by use of a unique CD3 derived from CRIS-7 vs. the CD3 used by other competitors. Mipletamig has received orphan drug designation ("orphan status") for AML according to the Orphan Drug Act. Mipletamig has been evaluated in 90 patients over two trials to date. RAINIER, Aptevo's Phase 1b/2 frontline AML program, was initiated in 3Q24.

About Aptevo Therapeutics

Aptevo Therapeutics Inc. is a clinical-stage biotechnology company focused on developing novel bispecific immunotherapies for the treatment of cancer. Aptevo is seeking to improve treatment outcomes and transform the lives of cancer patients. For more information, please visit www.aptevotherapeutics.com.

Safe Harbor Statement

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical fact, including, without limitation, statements regarding advancement of Aptevo's therapeutic candidates in clinical trials, including the initiation of the Phase 1b/2 dose optimization trial to further evaluate mipletamig in combination with venetoclax and azacitidine , whether the Phase 1b/2 protocol will be successful, whether further study of mipletamig in Phase 1b/2 trial focusing on a targeted patient population will continue to show clinical benefit, whether Aptevo's strategy will translate into an improved overall survival rate in acute myeloid leukemia, statements related to the durability of mipletamig and whether its duration of remission results will be indicative of later stage clinical trials, whether the mipletamig data in combination therapy and monotherapy will be indicative of later stage clinical trials, mipletamig's potential for multiple indications, the timing for its expected data readouts and whether this trial will establish a recommended Phase 2 dose, the potential use of any such candidate as therapeutics for treatment of disease, expectations about the safety, tolerability, efficacy and durability of its therapeutic candidate, statements regarding preclinical and clinical results and any suggestion that those results will be replicated in clinical development, the effectiveness of its ADAPTIR and ADAPTIR-FLEX platforms, and any other statements containing the words "may," "believes," "expects," "potential," "designed," "engineered," "innovative," "initiate," "allow," "promise," "plans," "will" and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based on Aptevo's current intentions, beliefs, and expectations regarding future events. Aptevo cannot guarantee that any forward-looking statement will be accurate. Investors should realize that if underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could differ materially from Aptevo's expectations. Investors are, therefore, cautioned not to place undue reliance on any forward-looking statement.

There are several important factors that could cause Aptevo's actual results to differ materially from those indicated by such forward-looking statements, including a deterioration in Aptevo's business or prospects; further assessment of preliminary or interim data or different results from later clinical trials; adverse events and unanticipated problems, adverse developments in clinical development, including unexpected safety issues observed during a clinical trial; adverse developments in the U.S. or global capital markets, credit markets or economies generally; and changes in regulatory, social, macroeconomic, and political conditions. For instance, actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including the uncertainties inherent in the initiation, enrollment and maintenance of patients in clinical trials, uncertainties inherent in the results of preliminary or interim data and preclinical and clinical studies being predictive of the results of later-stage clinical trials, the availability and timing of data from ongoing clinical trials, the trial design includes combination therapies that may make it difficult to accurately ascertain the benefits of mipletamig, expectations for the timing and steps required in the regulatory review process, expectations for regulatory approvals, the impact of competitive products, our ability to enter into agreements with strategic partners or raise funds on acceptable terms or at all and other matters that could affect the availability or commercial potential of the Company's product candidates, business or economic disruptions due to catastrophes or other events, including natural disasters or public health crises such as the novel coronavirus (referred to as COVID-19), geopolitical risks, including the current war between Russia and Ukraine as well as the war between Israel and Hamas, and macroeconomic conditions such as rising inflation and interests rates, increased market volatility and decreased consumer confidence. These risks are not exhaustive, Aptevo faces known and unknown risks. Additional risks and factors that may affect results are set forth in Aptevo's filings with the Securities and Exchange Commission, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2023, and its subsequent reports on Form 10-Q and current reports on Form 8-K. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from Aptevo's expectations in any forward-looking statement. Any forward-looking statement speaks only as of the date of this press release, and, except as required by law, Aptevo does not assume any obligation to update any forward-looking statement to reflect new information, events, or circumstances.

Aptevo Therapeutics
Miriam Weber Miller
Email: IR@apvo.com or millerm@apvo.com
Phone: 206-859-6629

SOURCE: Aptevo Therapeutics

View the original press release on accesswire.com

FAQ

What is the purpose of Aptevo's RAINIER trial for mipletamig (APVO436)?

The RAINIER trial aims to identify the recommended Phase 2 dose and evaluate safety, tolerability, and efficacy of mipletamig in combination with venetoclax and azacitidine for frontline acute myeloid leukemia (AML) patients.

What were the key results from previous trials of mipletamig (APVO436)?

Previous trials showed a 75% complete response rate among frontline patients, efficacy outcomes more than double the benchmarks, and a 91% clinical benefit rate in combination therapy for venetoclax naïve patients.

How many patients will be enrolled in the RAINIER trial for APVO?

The RAINIER trial will enroll up to 39 patients across five dose levels, ranging from 9 mcg to 140 mcg in combination with venetoclax and azacitidine.

What are the primary endpoints of the RAINIER trial for Aptevo's mipletamig?

The primary endpoints include evaluating safety and tolerability, determining the maximum tolerated dose, and assessing the incidence of cytokine release syndrome at each dose level.