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Advanced Solid TumorPhase 1/2NCT06090318

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

A Phase 1/2 study testing Milademetan and Atezolizumab in people with Advanced Solid Tumor and CDKN2A, run by Rain Oncology Inc.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Solid Tumor, CDKN2A, NSCLC
What is being tested?
Milademetan and Atezolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
19 May 2023to 30 May 2023
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
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  • 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

About this study

Official title: A Phase 1b/2Study of Milademetan in Combination With Atezolizumab in Patients With Advanced Solid Tumors With CDKN2A Loss (MANTRA-4)

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).

Read the detailed description

Up to 30 patients will be enrolled, 3 to 18 patients in the safety assessment cohort and 12 to 27 patients in the dose expansion cohort.

Being tested
Milademetan, Atezolizumab
Keywords
CDKN2A, WT TP53, Advanced Solid Tumor, Wild-type P53
Medical subject headings
Melanoma, Squamous Cell Carcinoma of Head and Neck, Carcinoma, Renal Cell, Mesothelioma, Stomach Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MilademetanDrug

    Also called RAIN-32

    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.

  • AtezolizumabDrug

    Also called TECENTRIQ

    1680mg administered every 4 weeks

Study groups in NCT06090318
Study groupRoleWhat they receive
Milademetan (RAIN-32) in Combination With AtezolizumabExperimentalMilademetan (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.
Receives: Drug: Milademetan; Drug: Atezolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 4 months

  2. 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

    Measured: 4 months

  3. 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

    Measured: 24 months

Secondary outcomes (8)

  1. Objective response rate (ORR)

    ORR, defined as the percentage of patients who achieve a confirmed CR or PR

    Measured: 24 months

  2. Duration of response (DOR)

    DOR, defined as the time from the date of first response (CR or PR) to the date of radiologically demonstrated disease progression, or death due to any cause

    Measured: 24 months

  3. Disease control rate (DCR)

    DCR, defined as the percentage of patients who achieve CR, PR, or SD for ≥ 16 weeks

    Measured: 24 months

  4. Progression Free Survival (PFS)

    PFS, defined as the time from the date of first dose to the earliest date of the first objective documentation of radiographic disease progression, or death due to any cause

    Measured: 24 months

  5. Growth Modulation Index (GMI)

    GMI: The GMI will be determined using the ratio of time to progression (TTP) with nth line of therapy (TTPn; here defined milademetan plus atezolizumab) to the most recent prior line of therapy (TTPn-1)

    Measured: 24 months

  6. Pharmacokinetics Cmax

    PK: maximum plasma concentration (Cmax) of milademetan

    Measured: Initiation of study treatment through milademetan dose 13, an average of 3 months

  7. Pharmacokinetics AUC

    PK: area under the plasma concentration-time curve (AUC)

    Measured: Initiation of study treatment through milademetan dose 13, an average of 3 months

  8. Pharmacokinetics Tmax

    PK: Time to reach maximum plasma concentration of milademetan

    Measured: Initiation of study treatment through milademetan dose 13, an average of 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Oct 2023
  2. Study start19 May 2023
  3. Primary completion30 May 2023
  4. Study completion30 May 2023

Why it stopped: Sponsor Decision

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06090318
Sponsor's protocol ID
RAIN-3204
Status last verified
Oct 2023
First submitted
14 Nov 2022
Last updated
19 Oct 2023
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Milademetan and Atezolizumab in people with Advanced Solid Tumor and CDKN2A, run by Rain Oncology Inc.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 19 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: 4 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06090318.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2023; AzTrials last refreshed its copy on 7 Nov 2026.

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