IACS-6274 With or Without Bevacizumab and Paclitaxel for the Treatment of Advanced Solid Tumors

NCT05039801 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2021-0265NCI-2021-09063
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

To find the highest tolerable dose of IACS-6274 that can be given alone, in combination with bevacizumab and paclitaxel, or in combination with capivasertib to patients who have solid tumors. The safety and tolerability of the study drug(s) will also be studied.

Conditions

Advanced Endometrial Carcinoma; Advanced Head and Neck Squamous Cell Carcinoma; Chondrosarcoma; Pathologic Stage IIIB Cutaneous Melanoma AJCC v8; Refractory Melanoma; Refractory Endometrial Carcinoma; Pathologic Stage III Cutaneous Melanoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Advanced Malignant Solid Neoplasm; Advanced Melanoma; Advanced Ovarian Clear Cell Adenocarcinoma; Clinical Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage IIIA Cutaneous Melanoma AJCC v8; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; Pathologic Stage IIID Cutaneous Melanoma AJCC v8; Pathologic Stage IV Cutaneous Melanoma AJCC v8; Recurrent Ovarian High Grade Serous Adenocarcinoma; Refractory Head and Neck Squamous Cell Carcinoma; Refractory Ovarian Clear Cell Adenocarcinoma; Refractory Ovarian High Grade Serous Adenocarcinoma; Stage III Ovarian Cancer AJCC v8; Stage III Uterine Corpus Cancer AJCC v8; Stage IIIA Ovarian Cancer AJCC v8; Stage IIIA Uterine Corpus Cancer AJCC v8; Stage IIIA1 Ovarian Cancer AJCC v8; Stage IIIA2 Ovarian Cancer AJCC v8; Stage IIIB Ovarian Cancer AJCC v8; Stage IIIB Uterine Corpus Cancer AJCC v8; Stage IIIC Ovarian Cancer AJCC v8; Stage IIIC Uterine Corpus Cancer AJCC v8; Stage IIIC1 Uterine Corpus Cancer AJCC v8; Stage IIIC2 Uterine Corpus Cancer AJCC v8; Stage IV Ovarian Cancer AJCC v8; Stage IV Uterine Corpus Cancer AJCC v8; Stage IVA Ovarian Cancer AJCC v8; Stage IVA Uterine Corpus Cancer AJCC v8; Stage IVB Ovarian Cancer AJCC v8; Stage IVB Uterine Corpus Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events (AEs)

  Will be assessed by the rate of dose limiting toxicities at each dose level in the dose escalation, and the rate of AEs and the rate of Grade 3 and higher AEs in the dose escalation and dose expansion. All AEs will be coded according to the latest version of Medical Dictionary for Regulatory Activities and National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0.

  Up to 90 days

Study Arms (3)

Part A (IACS-6274)

EXPERIMENTAL

Patients receive IACS-6274 PO throughout the study.

Drug: Glutaminase-1 Inhibitor IACS-6274

Part B (IACS-6274, bevacizumab, paclitaxel)

EXPERIMENTAL

Patients receive IACS-6274 PO, paclitaxel IV, and bevacizumab IV throughout the study.

Biological: Bevacizumab; Drug: Glutaminase-1 Inhibitor IACS-6274; Drug: Paclitaxel

PART C: (IACS-6274) with capivasertib

EXPERIMENTAL

Patients receive IACS-627 PO, with capivasertib PO throughout the study.

Drug: Glutaminase-1 Inhibitor IACS-6274; Drug: Capivasertib

Interventions

Bevacizumab BIOLOGICAL

Given IV

Also known as: ABP 215, Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF Monoclonal Antibody SIBP04, Anti-VEGF rhuMAb, Avastin, Bevacizumab awwb, Bevacizumab Biosimilar ABP 215, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar CBT 124, Bevacizumab Biosimilar CT-P16, Bevacizumab Biosimilar FKB238, Bevacizumab Biosimilar GB-222, Bevacizumab Biosimilar HD204, Bevacizumab Biosimilar HLX04, Bevacizumab Biosimilar IBI305, Bevacizumab Biosimilar LY01008, Bevacizumab Biosimilar MIL60, Bevacizumab Biosimilar Mvasi, Bevacizumab Biosimilar MYL-1402O, Bevacizumab Biosimilar QL 1101, Bevacizumab Biosimilar QL1101, Bevacizumab Biosimilar RPH-001, Bevacizumab Biosimilar SCT501, Bevacizumab Biosimilar Zirabev, Bevacizumab-awwb, Bevacizumab-bvzr, BP102, BP102 Biosimilar, HD204, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, Mvasi, MYL-1402O, QL1101, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF, SCT501, SIBP 04, SIBP-04, SIBP04, Zirabev

Part B (IACS-6274, bevacizumab, paclitaxel)

Glutaminase-1 Inhibitor IACS-6274 DRUG

Given by PO

Also known as: GLS1 Inhibitor IACS-6274, IACS 6274, IACS-6274, IACS6274, IPN 60090, IPN-60090, IPN60090

PART C: (IACS-6274) with capivasertib; Part A (IACS-6274); Part B (IACS-6274, bevacizumab, paclitaxel)

Paclitaxel DRUG

Given by IV (vein)

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Part B (IACS-6274, bevacizumab, paclitaxel)

Capivasertib DRUG

Given by PO

Also known as: AZD5363

PART C: (IACS-6274) with capivasertib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of written informed consent prior to any study related procedures and compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Male or female patients ≥18 years of age at the time of study entry who agree to participate by giving written informed consent prior to participation in any study related activities.
• Histologically or cytologically confirmed advanced solid tumors, specifically:
• Dose Escalation for Part A may include:
• Patients with tumors harboring actionable KEAP1/NFE2L2/STK11/NF1 mutations Patients with low ASNS expression levels (HGSOC or endometrial cancer) Patients who had immunotherapy (IO) melanoma (Minimum treatment duration of prior PD-1 or PD-L1-containing regimen of 12 weeks \[or equivalent of 2 response evaluations\]).
• Patients with post-platinum HNSCC Patients with chondrosarcoma Patients with ARID1A mutant clear cell ovarian cancer
• Dose Escalation for Part B may include:
• Confirmed recurrent high-grade non-mucinous ovarian cancer that is platinum-resistant, defined as disease relapse within a platinum-free interval (PFI, or the time elapsed from the last date of platinum dose until PD) of \< 6 months, and with less than 5 prior therapies
• Dose Expansion for Part B limited to:
• Confirmed recurrent high-grade non-mucinous ovarian cancer with low ASNS expression levels that is platinum-resistant, defined as disease relapse within a PFI of \< 6 months, and with less than 5 prior therapies.
• Dose Escalation for Part C may include:
• Patients with tumors harboring actionable KEAP1/NFE2L2 mutations Patients with tumors harboring PIK3CA hotspot mutations, activating AKT mutations, and inactivating PTEN mutations (irrespective of KEAP1/NFE2L2 mutations) Patients with low ASNS expression levels (HGSOC)
• Dose Expansion for Part C limited to:
• Patients with NSCLC with actionable KEAP1/NFE2L2 mutations Patients with HGSOClow ASNS expression levels (irrespective of biomarker status for KEAP1/NFE2L2)
• Patients must have received at least one line of therapy for advanced stage disease and be refractory or ineligible to available existing therapy(ies) known to provide clinical benefit for their condition.

You may not qualify if:

• Prior malignancy within the previous 2 years except for locally curable cancers that have been cured, such as basal or squamous cell skin cancer, or carcinoma in situ of the cervix, breast or bladder.
• Known primary central malignancy or symptomatic central nervous system metastasis(es).
• Note: Patients with stable, previously treated brain metastases may participate if neurologic symptoms have resolved, patients have been off steroids (at least 7 days for Part A and Part B, and at least 4 weeks for Part C), and there is no evidence of disease progression by imaging for at least 2 weeks before the first dose of study treatment.
• Uncontrolled, significant intercurrent or recent illness including, but not limited to, the following cardiac conditions:
• Any unstable cardiac arrhythmia within 6 months prior to enrolment
• Prolongation of the Fridericia corrected QT (QTcF) interval defined as \>450 ms for males and \>470 ms for females
• History of any of the following cardiovascular conditions within 6 months of enrolment:
• cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery bypass graft surgery, symptomatic peripheral vascular disease, class III or IV congestive heart failure, as defined by the New York Heart Association.
• Major surgical intervention within 28 days before study drug administration, or an anticipated need for major surgery during the study.
• Significant acute or chronic infections.
• Any psychiatric condition that would prohibit the understanding or rendering of informed consent.
• Treatment with strong cytochrome P450 subtype 3A4 (CYP3A4) inducers and inhibitors (including grapefruit juice) within 2 weeks of the first dose of study drug NOTE: patients must have stopped taking St. John's Wort 3 weeks prior to the start of treatment and stopped taking enzalutamide 4 weeks prior to the start of treatment.
• Treatment with strong CYP450 subtype 2D6 (CYP2D6) inhibitors or sensitive CYP3A4 substrates within 7 days of the first dose of study drug.
• Radiotherapy within 4 weeks prior to the start of study drug. Palliative radiotherapy for symptomatic control is acceptable if completed at least 2 weeks prior to study drug administration and no additional radiotherapy for the same lesion is planned.
• Underlying medical conditions (such as severe or uncontrolled systemic diseases, including uncontrolled hypertension, renal transplant and active bleeding diseases), for which in the investigator's opinion will make the administration of study drug hazardous or obscure the interpretation of toxicity determination or AEs.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Chondrosarcoma; Endometrial Neoplasms; Squamous Cell Carcinoma of Head and Neck; Melanoma; Ovarian Neoplasms

Interventions

Bevacizumab; Immunoglobulin G; Disulfides; Paclitaxel; Taxes; capivasertib

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations

Study Officials

• Timothy A Yap, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Timothy A Yap, MD

CONTACT

713-563-1930; tyap@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2021
• First Posted: September 10, 2021
• Study Start: September 30, 2021
• Primary Completion (Estimated): March 30, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: June 1, 2026

Record last verified: 2026-05

Locations

US (1)