Study of BMS-986466 with Adagrasib with or without Cetuximab in Participants with KRAS G12C-mutant Solid Tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bristol-Myers Squibb Services Unlimited Company

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

completed 13 May 2024

Decision date (initial)

2024-01-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-505070-15-00

WHO UTN

U1111-1296-8483

ClinicalTrials.gov

NCT06024174

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

1.To determine if the study treatment is safe and well-tolerated by the patients; to find the safe Maximum Tolerated Dose (MTD). If MTD is not reached the study will determine the Maximum Administered Dose (MAD). The study will identify dose levels for further testing: in Part 1A, BMS-986466 will be given with adagrasib to patients with advanced KRAS G12C mutant NSCLC, CRC, Pancreatic Duct Adenocarcinoma (PDAC), and Biliary Tract Cancer (BTC). In Part 1B, BMS-986466 will be given with adagrasib and cetuximab to participants with advanced KRAS G12C mutant CRC.
2.To determine if the study treatment is effective against cancer: - Part 2A: BMS-986466 given with adagrasib versus adagrasib alone in KRAS G12C mutant NSCLC naive to treatment with KRAS G12C inhibitor (G12Ci naive) -Part 2B: BMS-986466 given with adagrasib with or without cetuximab versus adagrasib plus cetuximab in KRAS G12C mutant, G12Ci naive CRC.

Secondary objectives 4

1. In Parts 1 and 2: To determine the Pharmacokinetic (PK) profile (how drug is absorbed and processed in body) of BMS-986466 after first dose and at steady state in combination with adagrasib with or without cetuximab.
2. To evaluate the initial effectiveness of above combinations in KRAS G12C mutant NSCLC (G12Ci naive) in Part 2A and in participants with KRAS G12C-mutant CRC (G12Ci naïve) in Part 2B.
3. To assess safety and tolerability of combinations in KRAS G12C mutant NSCLC (G12Ci naive) in Part 2A and in KRAS G12C-mutant CRC (G12Ci naïve) in Part 2B.
4. To study the Pharmacodynamic (PD) profile of BMS986466 (how drug affects the body).

Conditions and MedDRA coding

Oncology, NSCLC and CRC

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Part 1: Individuals with a confirmed diagnosis of advanced KRAS G12C mutant NSCLC, CRC, PDAC and BTC that has spread to other parts of the body and cannot be removed surgically, may or may not have received previous treatment with KRAS G12C inhibitors.
2. Part 1: For NSCLC and CRC: Participants must have a documented KRAS G12C mutation from an approved test and when such result is not available, positive KRAS G12C mutation status should be confirmed by a central laboratory at the time of screening.
3. Part 1: For PDAC and BTC: Participants must have a documented KRAS G12C mutation from an approved test.
4. Part 1: Have failed, are intolerant or recurrence after available standard of care treatments.
5. Part 2: Individuals must have a confirmed diagnosis of advanced KRAS G12C-mutant NSCLC (Part 2A) or CRC (Part 2B) that has spread to other parts of the body and cannot be removed surgically and are G12C inhibitors naive.
6. Part 2: Participants must have a documented KRAS G12C mutation from an approved test and when such result is not available, positive KRAS G12C mutation status should be confirmed by a central laboratory at the time of screening.
7. Part 2: Have failed, are intolerant or recurrence after at least 1 previous line of therapy.

Exclusion criteria 3

1. Have tumors with known BRAF V600X, PTPN11 or KRAS Q61X mutations.
2. Have or any significant heart disease or condition.
3. Receiving any medications that are substrate of CYP3A4 or inducers and/ or inhibitors.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Incidence of Dose Limiting Toxicities, Adverse Events, Serious Adverse Events, Adverse Events leading to discontinuation, and deaths.
2. Overall Response Rate (ORR) per RECIST v1.1 by Blinded Independent Central Review (BICR).

Secondary endpoints 4

1. Summary measures of BMS-986466 PK parameters in plasma including Maximum concentration (Cmax), Time to maximum concentration (Tmax), and Area Under the Curve (AUC(0-T)) from concentration-time data.
2. Progression Free Survival (PFS), Disease Control Rate (DCR), Duration of Response (DOR), and Time To Response (TTR) per RECIST v1.1 by BICR.
3. Incidence of Dose Limiting Toxicities, Adverse Events, Serious Adverse Events, Adverse Events leading to discontinuation, and deaths.
4. Summery measures of target engagement (ability of a drug to bind to a specific molecule)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bristol-Myers Squibb Services Unlimited Company

Sponsor organisation

Bristol-Myers Squibb Services Unlimited Company

Address

Plaza 254 Blanchardstown Corporate Park 2, Ballycoolin Ballycoolin

City

Dublin 15

Postcode

D15 T867

Country

Ireland

Scientific contact point

Organisation

Bristol-Myers Squibb Services Unlimited Company

Contact name

GSM-CT

Public contact point

Organisation

Bristol-Myers Squibb Services Unlimited Company

Contact name

GSM-CT

Third parties 9

Locations

5 EU/EEA countries · 18 investigational sites

By country

Investigational sites

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications