Acapatamab for Prostate Cancer

No longer recruiting at 38 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Amgen

Must be taking: GnRH agonist/antagonist

Must not be taking: Strong OAT3 inhibitors

Disqualifiers: CNS metastases, Autoimmune disease, Cardiac arrhythmia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called acapatamab for individuals with advanced prostate cancer that does not respond to standard hormone therapy. The main goal is to determine the treatment's safety and identify the optimal dose. Participants may receive acapatamab alone or with other medications. It suits those with a confirmed diagnosis of metastatic castration-resistant prostate cancer who have tried and not responded to at least one type of chemotherapy. As a Phase 1 trial, this research aims to understand how acapatamab works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop any anticancer therapy or immunotherapy at least 4 weeks before starting the study, except for certain hormone therapies. If you are on chronic systemic corticosteroid therapy, you need to stop it 7 days before the first dose.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that acapatamab, a new cancer treatment, has been tested for safety and tolerability. Earlier studies found it to be safe, with manageable side effects. One concern was cytokine release syndrome (CRS), a reaction some people experience with similar treatments. However, the side effects were generally manageable.

For the combination of acapatamab and pembrolizumab, studies are ongoing, and specific safety information is still being gathered. This means a complete picture of the combination's safety is not yet available.

In another study, acapatamab was combined with etanercept to better manage CRS. Early results suggested that adding etanercept might help reduce some side effects.

Overall, since acapatamab is in a phase 1 trial, it remains in the early stages of human testing. This phase primarily assesses safety and helps determine the best dose for future studies. So far, it has shown promise in terms of safety, but more research is needed to confirm these findings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about acapatamab because it represents a novel approach to treating metastatic castration-resistant prostate cancer (mCRPC). Unlike traditional treatments like hormonal therapies or chemotherapy, acapatamab is a bispecific T-cell engager antibody that targets both prostate-specific membrane antigen (PSMA) and CD3 on T-cells, potentially enhancing the body's own immune response against the cancer cells. This dual-targeting mechanism can lead to more precise and potent action against tumor cells. Additionally, acapatamab's administration in combination with drugs like pembrolizumab and etanercept, or its interaction studies with the cytochrome P450 cocktail, provides a multi-faceted approach to explore different therapeutic synergies and manage potential side effects, offering new hope for patients with limited options.

What evidence suggests that acapatamab might be an effective treatment for metastatic castration-resistant prostate cancer?

Research has shown that acapatamab, a new treatment for prostate cancer, shows early signs of effectiveness. It aids the immune system in identifying and attacking cancer cells. Early studies indicate it is safe and generally well-tolerated, with some patients experiencing a decrease in tumor activity. In this trial, some participants will receive acapatamab alone, while others will receive it with pembrolizumab, another cancer treatment that might further boost the immune system's fight against cancer. Although these results are promising, they remain in the early stages, and further research is needed to fully understand its effects. ^{1 3 6 7 8}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

Inclusion Criteria

- nodal or visceral progression as defined by RECIST 1.1 with PCGW3 modifications

Subjects with histologically or cytologically confirmed mCRPC who are refractory to a novel antiandrogen therapy (abiraterone, enzalutamide, and/or apalutamide) and have failed at least 1 (but not more than 2) taxane regimens (or who are deemed medically unsuitable to be treated with a taxane regimen or have actively refused treatment with a taxane regimen). Progression on novel antiandrogen therapy may have occurred in the non-metastatic CRPC setting

Subject has provided informed consent prior to initiation of any study specific activities/procedures

Exclusion Criteria

Prior PSMA-targeted therapy (subjects on prior therapy may be eligible if discussed with Amgen medical monitor prior to enrollment)

Needing chronic systemic corticosteroid therapy (prednisone > 10 mg per day or equivalent) or any other immunosuppressive therapies (including anti-tumor necrosis factor alpha [TNF alpha] therapies) unless stopped 7 days prior to start of first dose

Any anticancer therapy or immunotherapy within 4 weeks of start of first dose, not including luteinizing hormone-releasing hormone agonist (LHRH)/GnRH analogue (agonist/antagonist). Subjects on a stable bisphosphonate or denosumab regimen for >/= 30 days prior to randomization are eligible

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-exploration

Acapatamab is administered intravenously to estimate the maximum tolerated dose (MTD) and identify the recommended phase 2 dose (RP2D) based on emerging safety, efficacy, and pharmacodynamic data.

Up to 3 years

Treatment

Participants receive acapatamab alone or in combination with pembrolizumab, etanercept prophylaxis, or CYP phenotyping cocktail, with monitoring for safety and efficacy.

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of prostate-specific antigen (PSA) response and progression-free survival.

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Acapatamab

How Is the Trial Designed?

Group I: Part 6: acapatamab + Cytochrome P450 (CYP) Cocktail Drug Interaction Experimental Treatment 2 Interventions

Part 6: acapatamab is administered intravenously at RP2D/MTD. A CYP phenotyping cocktail will be administered orally.

Group II: Part 5: acapatamab Outpatient Cohort Experimental Treatment 1 Intervention

Part 5: acapatamab is administered intravenously at RP2D/MTD in an outpatient setting with 8-hour monitoring.

Group III: Part 4: acapatamab 24 Hour Monitoring Experimental Treatment 1 Intervention

Part 4: acapatamab is administered intravenously at RP2D/MTD with 24-hour monitoring.

Group IV: Part 3: acapatamab + Etanercept Prophylaxis Experimental Treatment 2 Interventions

Part 3: acapatamab is administered intravenously at RP2D/MTD levels. Etanercept will be administered subcutaneously in cycle 1 only.

Group V: Part 2: acapatamab + Pembrolizumab Experimental Treatment 2 Interventions

Part 2: acapatamab is administered intravenously at the MTD/RP2D. Pembrolizumab will be administered intravenously.

Group VI: Part 1 Dose-exploration: acapatamab treatment Experimental Treatment 1 Intervention

Part 1 dose-exploration: acapatamab is administered intravenously. The dose-exploration phase of the study will estimate the MTD of acapatamab. RP2D may be identified based on emerging safety, efficacy, and pharmacodynamic data prior to reaching an MTD.

Group VII: Part 1 Dose-expansion: acapatamab treatment Experimental Treatment 1 Intervention

Part 1 dose-expansion: acapatamab is administered intravenously at the MTD/RP2D.

Who Is Running the Clinical Trial?

Amgen

Lead Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11395298/

A PHASE 1 STUDY OF ACAPATAMAB, A HALF-LIFE ... Acapatamab was safe and tolerated and had a manageable CRS profile. Preliminary signs of efficacy with limited durable antitumor activity were ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03792841

Study Details | NCT03792841 | Safety, Tolerability, ... This is a phase I, first-in-human study to evaluate the safety and tolerability of acapatamab; a half-life extended (HLE) bispecific T-cell engager (BiTE®) ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38300720/

A Phase I Study of Acapatamab, a Half-life Extended, PSMA ... Acapatamab was safe and tolerated and had a manageable CRS profile. Preliminary signs of efficacy with limited durable antitumor activity were observed.

4. aacrjournals.org aacrjournals.org/clincancerres/article-abstract/30/8/1488/742131/A-Phase-I-Study-of-Acapatamab-a-Half-life-Extended?redirectedFrom=fulltext

A Phase I Study of Acapatamab, a Half-life Extended, PSMA ... Acapatamab was safe and tolerated and had a manageable CRS profile. Preliminary signs of efficacy with limited durable antitumor activity were observed.

5. clin.larvol.com clin.larvol.com/trial-detail/NCT03792841

Safety, Tolerability, Pharmacokinetics, and Efficacy of ... Decision-enabling data are expected in H1 2022. A master protocol evaluating combinations with acapatamab continues to enroll patients with earlier-line mCRPC; ...

6. dcchemicals.com dcchemicals.com/msds/MSDS_A113.html

Acapatamab Biosimilar|2314491-93-3|MSDS 2. HAZARDS IDENTIFICATION ; H302. Harmful if swallowed. ; H410. Very toxic to aquatic life with long lasting effects. ; P264. Wash skin thoroughly after handling.

7. medchemexpress.com medchemexpress.com/acapatamab.html?srsltid=AfmBOoqtXQinx3SqYlbJu6uHuseVyERAqxrmIgqbzg4PYZN3Bv4yak6u

Acapatamab (AMG-160) | Anti-CD3E/FOLH1 Antibody Acapatamab (0.02-2 mg/kg; i.v.; days 16, 23, and 31) has antitumor activity and inhibits tumor growth in NOD/SCID mice with 22Rv-1 CRPC xenografts.

8. amgentrials.com amgentrials.com/study/?id=20180101&utm_source=Patient_Summary&utm_medium=website&utm_campaign=AMG160&utm_id=ClinicalTrials

Safety, Tolerability, Pharmacokinetics, and Efficacy of ... The dose-exploration phase of the study will estimate the MTD of acapatamab. RP2D may be identified based on emerging safety, efficacy, and pharmacodynamic data ...