ALTA3263 for Cancer

Recruiting at 6 trial locations

Overseen By Alterome Clinical Trial Contact Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Alterome Therapeutics, Inc.

Must not be taking: KRAS inhibitors

Disqualifiers: Inability to swallow, others

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

Compensation: Varies

Number of Visits: 1

188 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ALTA3263 for individuals with advanced solid tumors that have a specific genetic change known as a KRAS mutation. The main goal is to assess the safety and tolerability of ALTA3263. It targets patients whose cancer cannot be surgically removed or has metastasized, and who have not responded to previous treatments. Those with a solid tumor cancer featuring a KRAS mutation, for whom prior treatments were ineffective, may find this trial suitable. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in humans.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that ALTA3263 is likely to be safe for humans?

Research has shown that ALTA3263 has potential based on early lab studies. It was well-tolerated in animals, meaning it didn't cause major side effects. ALTA3263 is a pill designed to target KRAS mutations, which are common in some advanced cancers. This trial marks the first time it is being tested in humans. As an early-stage trial, the main goal is to assess the safety of ALTA3263 for people. Although detailed information from human studies is not yet available, advancing to human trials indicates it was safe enough in earlier tests to warrant further research. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

ALTA3263 is unique because it introduces a new approach to cancer treatment by utilizing a novel mechanism of action. Unlike typical cancer therapies that target dividing cells indiscriminately, ALTA3263 is designed to specifically target cancer cells based on their unique molecular markers, potentially reducing damage to healthy cells. This precision targeting could lead to fewer side effects and improved effectiveness. Researchers are excited about ALTA3263 because it represents a significant advancement in personalized cancer therapy, offering hope for better outcomes in patients who may not respond well to existing treatments.

What evidence suggests that ALTA3263 might be an effective treatment for cancer?

Research has shown that ALTA3263, the treatment under study in this trial, could be a promising option for advanced solid tumors with KRAS mutations. This treatment targets and blocks the active form of these mutations, which are common in many cancers. In early lab studies, ALTA3263 caused significant tumor shrinkage in models with KRAS mutations. The treatment was well-tolerated, meaning it did not cause severe side effects in these studies. Although information from human trials is limited, the strong early results suggest it could be effective against these types of tumors. ^{1 4 5 6 7}

Who Is on the Research Team?

Study Medical Director

Principal Investigator

Alterome Therapeutics

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that have a specific change called KRAS mutations. It's open to those with certain types of cancer, including colorectal, non-small cell lung cancer, and pancreatic cancer.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

My organs are working well.

My cancer has a KRAS mutation confirmed by a certified test.

Exclusion Criteria

I have previously been treated with a KRAS inhibitor.

I cannot swallow or absorb pills due to a medical condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive ALTA3263 at increasing doses to determine the maximum tolerated dose

21 days per cycle

Cycle 1 Day 1 and Day 15: Predose and up to 24 hours postdose

Dose Expansion

Participants receive ALTA3263 at the determined dose to further evaluate safety and efficacy

21 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 39 months

What Are the Treatments Tested in This Trial?

Interventions

• ALTA3263

Trial Overview

The study is testing the safety and how well people can handle ALTA3263, a new treatment for cancers with KRAS mutations. Participants will receive this experimental drug to see its effects.

How Is the Trial Designed?

Group I: ALTA3263 monotherapy Experimental Treatment 1 Intervention

ALTA3263 will be administered continuously at a protocol-defined dose based on cohort assignment

Group II: ALTA3263 in combination with cetuximab Experimental Treatment 2 Interventions

ALTA3263 in combination with cetuximab will be administered continuously at a protocol-defined dose based on cohort assignment

Who Is Running the Clinical Trial?

Alterome Therapeutics, Inc.

Lead Sponsor

Trials

2

Recruited

240+

Published Research Related to This Trial

Aprepitant, a selective NK(1) receptor antagonist, has been shown to be well tolerated and significantly improves the management of chemotherapy-induced nausea and vomiting when added to standard treatments like 5-HT3 receptor antagonists and corticosteroids.

While aprepitant enhances efficacy in preventing nausea and vomiting during chemotherapy, it can interact with other medications due to its effect on cytochrome P450 3A4, necessitating careful management of drug combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aprepitant--where do we stand in the control of chemotherapy-induced nausea and vomiting? Sarcev, T., Secen, N., Zaric, B., et al.[2018]

In a phase 3 trial involving 307 pediatric patients aged 6 months to 17 years, aprepitant significantly improved the prevention of chemotherapy-induced nausea and vomiting, with 51% of patients achieving a complete response compared to 26% in the control group (p<0.0001).

The safety profile of aprepitant was comparable to the control, with the most common serious adverse events being febrile neutropenia, indicating that aprepitant can be safely used in combination with ondansetron for children undergoing chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aprepitant for the prevention of chemotherapy-induced nausea and vomiting in children: a randomised, double-blind, phase 3 trial. Kang, HJ., Loftus, S., Taylor, A., et al.[2018]

In the phase III ALTA-1L trial, the ALK inhibitor brigatinib demonstrated superior efficacy compared to crizotinib in patients with untreated non-small cell lung cancer, leading to longer progression-free survival.

Brigatinib also showed a higher objective response rate and greater effectiveness against brain metastases, while being less harmful to patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brigatinib Outperforms Crizotinib as First-Line Therapy. [2020]

The (177)Lu-labeled huA33 monoclonal antibody specifically targets colorectal cancer cells, showing a high tumor uptake of 134% ID/g at 72 hours post-injection, indicating its potential effectiveness in treating colorectal carcinoma.

The biodistribution study demonstrated low uptake in normal tissues and a high tumor-to-blood ratio (70) after 10 days, suggesting that (177)Lu-huA33 is stable and could be a promising candidate for radioimmunotherapy with minimal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro and in vivo characterization of 177Lu-huA33: a radioimmunoconjugate against colorectal cancer. Almqvist, Y., Steffen, AC., Tolmachev, V., et al.[2013]

The study demonstrated that the humanized antibody huA33, when combined with capecitabine, can specifically target metastatic colorectal cancer while minimizing exposure to normal tissues, showing excellent tumor localization and safety in 19 enrolled patients.

The treatment was well-tolerated, with manageable side effects, and resulted in one partial response and stable disease in 10 patients, indicating potential efficacy for delivering targeted chemoradiation in colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted chemoradiation in metastatic colorectal cancer: a phase I trial of 131I-huA33 with concurrent capecitabine. Herbertson, RA., Tebbutt, NC., Lee, FT., et al.[2020]

In the ALTA-1L phase 3 trial, first-line treatment with brigatinib significantly improved quality-adjusted survival time without symptoms or toxicity compared to crizotinib in patients with ALK-positive non-small cell lung cancer, with a mean Q-TWiST of 28.2 months versus 25.1 months (P = 0.045).

Patients with brain metastases treated with brigatinib experienced even greater benefits, achieving a mean Q-TWiST of 29.0 months compared to 19.0 months for those on crizotinib (P = 0.0001), highlighting brigatinib's efficacy in a challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Q-TWiST analysis of survival benefits with brigatinib versus crizotinib in patients with anaplastic lymphoma kinase-positive non-small cell lung cancer based on results of the ALTA-1L trial. Garcia Campelo, MR., Wan, Y., Lin, HM., et al.[2023]

The monoclonal antibody (124)I huA33 effectively targets colorectal cancer, showing good localization in tumors with a median uptake significantly higher than in normal colon tissue, indicating its potential for cancer imaging and treatment.

The study found no significant toxicity associated with (124)I huA33, and the pharmacokinetics were consistent across different administration routes, confirming its safety and efficacy in patients with colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

(124)I-huA33 antibody PET of colorectal cancer. Carrasquillo, JA., Pandit-Taskar, N., O'Donoghue, JA., et al.[2021]

In a study of 20 cancer patients receiving cisplatin chemotherapy, the addition of aprepitant (APR) to standard antiemetic therapy significantly reduced vomiting and improved appetite over a 5-day period compared to conventional therapy.

Aprepitant was well-tolerated with no reported adverse events, suggesting it is a safe and effective option for managing nausea, vomiting, and appetite loss in patients undergoing chemotherapy with highly emetic drugs like cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Antiemetic effect of aprepitant in cancer patients receiving Cisplatin regimen]. Yakabe, T., Mochinaga, S., Fujito, H., et al.[2018]

In the ALTA-1L study, brigatinib significantly prolonged progression-free survival and improved health-related quality of life (HRQOL) compared to crizotinib in patients with advanced ALK-positive non-small cell lung cancer, with a median time to worsening in global health status of 26.74 months for brigatinib versus 8.31 months for crizotinib.

Brigatinib not only delayed the time to worsening in various quality of life measures but also showed a longer duration of improvement in global health status and several functional and symptom scales, indicating it may offer better overall quality of life benefits for patients compared to crizotinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality of life in the randomized phase III trial of brigatinib vs crizotinib in advanced ALK inhibitor-naive ALK + non-small cell lung cancer (ALTA-1L). Garcia Campelo, MR., Lin, HM., Zhu, Y., et al.[2021]

In a study of 64 patients undergoing high-dose chemotherapy, the combination of aprepitant, granisetron, and dexamethasone achieved complete response rates of 83% for acute and 70% for delayed nausea/vomiting, indicating its effectiveness in managing chemotherapy-induced symptoms.

The addition of aprepitant to the standard antiemetic regimen was well-tolerated over 4-5 days, suggesting it could enhance the prevention of nausea and vomiting without increasing side effects compared to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The NK-1 receptor-antagonist aprepitant in high-dose chemotherapy (high-dose melphalan and high-dose T-ICE: paclitaxel, ifosfamide, carboplatin, etoposide): efficacy and safety of a triple antiemetic combination. Jordan, K., Jahn, F., Jahn, P., et al.[2018]

This Phase III study (ALTA-3) will compare the effectiveness of two next-generation ALK inhibitors, brigatinib and alectinib, in patients with ALK+ non-small-cell lung cancer (NSCLC) who have progressed on crizotinib, aiming to improve progression-free survival.

The study will assess progression-free survival as the primary endpoint and overall survival as a key secondary endpoint, providing valuable insights into optimizing treatment for patients with advanced ALK+ NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brigatinib vs alectinib in crizotinib-resistant advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer (ALTA-3). Popat, S., Liu, G., Lu, S., et al.[2022]

The conditionally replicative adenovirus AV22EL, controlled by the A33 promoter, specifically targets and destroys colorectal cancer (CRC) cells while sparing normal cells, demonstrating its potential as a safe treatment option.

In preclinical studies, AV22EL significantly reduced tumor growth and eliminated established hepatic metastases in over 90% of mice, showing strong efficacy and improved survival rates without toxic effects on normal tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel A33 promoter-based conditionally replicative adenovirus suppresses tumor growth and eradicates hepatic metastases in human colon cancer models. Cafferata, EG., Macció, DR., Lopez, MV., et al.[2022]

In a study involving 11 patients with advanced chemotherapy-resistant colorectal cancer, the humanized A33 monoclonal antibody (huA33) showed potential antitumor effects, with one patient achieving a partial response and four others maintaining stable disease for up to 12 months.

However, huA33 was found to be immunogenic in 73% of patients, leading to significant infusion-related toxicities in some, suggesting that while it has therapeutic potential, its immunogenicity may limit its use and indicates a need for less immunogenic versions of the antibody.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of anticolon cancer humanized antibody A33. Welt, S., Ritter, G., Williams, C., et al.[2007]

In a study of 141 patients undergoing high-emetogenic chemotherapy, the OLN10 group experienced significantly less severe nausea compared to the APR group, with fewer patients reporting grades 2-4 nausea (8.7% vs. 27.7%).

The overall efficacy in preventing chemotherapy-induced nausea and vomiting (CINV) was comparable between OLN5 and APR, indicating that OLN5 may be a viable alternative for CINV prophylaxis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, double-blind, placebo-controlled study of aprepitant versus two dosages of olanzapine with ondansetron plus dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients receiving high-emetogenic chemotherapy. Ithimakin, S., Theeratrakul, P., Laocharoenkiat, A., et al.[2020]

In the final analysis of the ALTA-1L study involving 275 patients, brigatinib demonstrated significantly better progression-free survival (PFS) compared to crizotinib, with a 3-year PFS of 43% versus 19%, indicating its superior efficacy in treating advanced ALK-positive NSCLC.

Brigatinib also showed potential overall survival benefits in patients with brain metastases, suggesting it may be particularly effective for this subgroup, while maintaining a favorable safety profile with no new safety concerns reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brigatinib Versus Crizotinib in ALK Inhibitor-Naive Advanced ALK-Positive NSCLC: Final Results of Phase 3 ALTA-1L Trial. Camidge, DR., Kim, HR., Ahn, MJ., et al.[2022]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06835569

A Study to Learn About Study Medicine ALTA3263 in ...

The purpose of this study is to characterize the safety and tolerability of ALTA3263 in adults with advanced solid tumors with KRAS mutations. Detailed ...

2.

firstwordpharma.com

firstwordpharma.com/story/5941005

Alterome Doses First Patient in Phase 1 Study of ...

ALTA3263 is an oral KRAS-selective inhibitor specifically designed to potently inhibit the KRAS “ON” (active) state of greater than 90% of all KRAS mutations.

3.

withpower.com

withpower.com/trial/phase-1-colorectal-neoplasms-2-2025-57526

ALTA3263 for Cancer

The drug brigatinib, which may be related to ALTA3263, has shown to be more effective than crizotinib in treating non-small cell lung cancer, leading to longer ...

4.

trial.medpath.com

trial.medpath.com/news/216a4831372ddcf2/alterome-therapeutics-initiates-phase-1-trial-of-novel-pan-kras-inhibitor-alta3263-for-advanced-solid-tumors

Alterome Therapeutics Initiates Phase 1 Trial of Novel Pan ...

In preclinical studies, ALTA3263View drug details led to deep tumor regressions in multiple KRAS mutant models while being well-tolerated during ...

5.

finance.yahoo.com

finance.yahoo.com/news/alterome-doses-first-patient-phase-113000865.html

Alterome Doses First Patient in Phase 1 Study of ...

ALTA3263 led to deep regressions in multiple KRAS mutant preclinical models while being well-tolerated during prolonged oral dosing. These data ...

6.

biospace.com

biospace.com/press-releases/alterome-doses-first-patient-in-phase-1-study-of-alta3263-a-novel-pan-kras-dual-on-off-inhibitor-in-advanced-solid-tumors

Alterome Doses First Patient in Phase 1 Study of ...

ALTA3263 is an oral KRAS-selective inhibitor specifically designed to potently inhibit the KRAS “ON” (active) state of greater than 90% of all KRAS mutations.

7.

ctv.veeva.com

ctv.veeva.com/study/a-phase-1-1b-multiple-cohort-trial-of-alta3263-in-patients-with-advanced-solid-tumors-with-kras-muta

A Study to Learn About Study Medicine ALTA3263 in Adults ...

The purpose of this study is to characterize the safety and tolerability of ALTA3263 in adults with advanced solid tumors with KRAS mutations.