Milademetan in Combination With Atezolizumab in Patients With Advanced Solid Tumors With CDKN2A Loss

NCT06090318 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: RAIN-3204
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is an open-label, single-arm, Phase 1b/2 study designed to evaluate the safety, tolerability, and preliminary efficacy of milademetan in combination with atezolizumab in patients with advanced solid tumors with confirmed homozygous CDKN2A loss and WT TP53 who have progressed on or are refractory to prior PD-1/PD-L1 inhibitor therapy and who, in the opinion of the Investigator, are unlikely to tolerate or derive clinically meaningful benefit from other therapy. This study will determine the recommended dose of milademetan when given in combination with atezolizumab (the combination RP2D) using a dose de-escalation safety assessment cohort (Phase 1b). Following identification of the combination RP2D, the safety profile and preliminary anti-tumor activity of the combination RP2D will be evaluated in a larger population in a dose expansion cohort (Phase 2).

Conditions

Advanced Solid Tumor; CDKN2A; NSCLC; Urothelial Carcinoma Bladder; Melanoma; Pancreas Adenocarcinoma; HNSCC; Renal Cell Carcinoma; Mesothelioma; Gastric Cancer

Keywords

CDKN2A; WT TP53; Advanced Solid Tumor; Wild-type P53

Outcome Measures

Primary Outcomes (3)

• The number of participants with treatment related AEs meeting DLT-defined criteria assessed by CTCAE v5.0 when receiving milademetan in combination with atezolizumab in patients with advanced solid tumors with HZ CDKN2A loss and WT TP53

  4 months

• The appropriate dose of milademetan in combination with atezolizumab based on the number of participants with DLT-defined adverse events assessed by CTCAE v5.0 criteria

  4 months

• Treatment emergent AE of the identified RP2D of milademetan in combination with atezolizumab in patients with advanced solid tumors with HZ CDKN2A loss and WT TP53

  24 months

Secondary Outcomes (8)

• Objective response rate (ORR)

  24 months

• Duration of response (DOR)

  24 months

• Disease control rate (DCR)

  24 months

• Progression Free Survival (PFS)

  24 months

• Growth Modulation Index (GMI)

  24 months

Study Arms (1)

Milademetan (RAIN-32) in Combination With Atezolizumab

EXPERIMENTAL

Milademetan (RAIN-32): 260 mg orally on 3 consecutive day sets with a minimum of 14 days and a maximum of 21 days between the first day of each 3- day dosing set. Atezolizumab: Atezolizumab IV infusion is to be administered on Day 1 of each 28- day cycle.

Drug: Milademetan; Drug: Atezolizumab

Interventions

Milademetan DRUG

260 mg once daily orally on 3 consecutive day sets with a minimum of 14 days and a maximum of 21 days between the first day of each 3- day dosing set.

Also known as: RAIN-32

Milademetan (RAIN-32) in Combination With Atezolizumab

Atezolizumab DRUG

1680mg administered every 4 weeks

Also known as: TECENTRIQ

Milademetan (RAIN-32) in Combination With Atezolizumab

Eligibility Criteria

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

You may qualify if:

• Has a histologically confirmed, advanced solid tumor that has progressed on prior therapy with an anti-PD-1/L1 inhibitor administered as either monotherapy or in combination with other therapies
• Has documented homozygous CDKN2A loss and Wild-Type TP53
• Confirmation of available tumor tissue collected within 5 years of enrollment
• Measurable tumor lesions per RECIST 1.1
• Estimate life expectancy of at least 6 months
• ECOG PS of 0 or 1
• Resolution of clinically relevant toxic effect of prior anti-cancer therapies Note: AEs from prior therapy must resolve to Grade ≤ 1 per the NCI CTCAE version 5.0, except for peripheral neuropathy, which must resolve to Grade ≤ 2, and alopecia
• Adequate bone marrow, renal and hepatic function

You may not qualify if:

• Has received prior treatment with any MDM2 inhibitor; prior treatment with atezolizumab is allowed except if the patient discontinued due to toxicity
• Has a history of any Grade 3 or 4 immune-related toxicities to a prior checkpoint inhibitor treatment or history of treatment discontinuation with prior checkpoint inhibitor use due to toxicity
• Endocrinopathies which are stable with appropriate hormonal supplementation consistent with other eligibility parameters
• Dermatologic events which have resolved to Grade ≤ 1 on stable medication, as appropriate, and consistent with other eligibility parameters
• Treatment with systemic immunosuppressive medication, including but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and antitumor necrosis factor agents, within 2 weeks prior to the first dose of study treatment or anticipation of need for systemic immunosuppressive medication during the course of the study
• Has an uncontrolled infection within the 7 days prior to Screening
• Has undergone treatment with therapeutic oral or IV antibiotics within 2 weeks prior to first dose of study treatment
• Has known active central nervous metastases and/or carcinomatous meningitis. Note: Patients who require steroids for brain metastases must be on a stable or tapering dose of corticosteroids for at least 2 weeks before the first dose of study treatment. If applicable, patients must complete stereotactic radiosurgery 7 days before, and spinal or whole brain radiotherapy 21 days before, their first dose of study treatment
• Has as other primary malignancies that have required systemic antineoplastic treatment within 2 years prior to Screening, except for localized cancers that have apparently been cured (eg, nonmelanoma skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast) and will not interfere with the study outcomes
• Has uncontrolled or significant cardiovascular disease

Sponsors & Collaborators

• Rain Oncology Inc: lead

MeSH Terms

Conditions

Melanoma; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Renal Cell; Mesothelioma; Stomach Neoplasms

Interventions

milademetan; atezolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Adenocarcinoma; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Adenoma; Neoplasms, Mesothelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2022
• First Posted: October 19, 2023
• Study Start: May 19, 2023
• Primary Completion: May 30, 2023
• Study Completion: May 30, 2023
• Last Updated: October 19, 2023

Record last verified: 2023-10