Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04956640




Registration number
NCT04956640
Ethics application status
Date submitted
2/07/2021
Date registered
9/07/2021
Date last updated
24/05/2024

Titles & IDs
Public title
Study of LY3537982 in Cancer Patients With a Specific Genetic Mutation (KRAS G12C)
Scientific title
A Phase 1/2 Study of LY3537982 in Patients With KRAS G12C-Mutant Advanced Solid Tumors
Secondary ID [1] 0 0
2021-000595-12
Secondary ID [2] 0 0
LOXO-RAS-20001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Non-Small-Cell Lung 0 0
Colorectal Neoplasms 0 0
Endometrial Neoplasms 0 0
Ovarian Neoplasms 0 0
Pancreatic Neoplasms 0 0
Biliary Tract Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Pancreatic
Cancer 0 0 0 0
Ovarian and primary peritoneal
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)
Cancer 0 0 0 0
Biliary tree (gall bladder and bile duct)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - LY3537982
Treatment: Drugs - Pembrolizumab
Treatment: Drugs - Cetuximab
Treatment: Drugs - Pemetrexed
Treatment: Drugs - Cisplatin
Treatment: Drugs - Carboplatin

Experimental: LY3537982 (Dose Escalation) - LY3537982 administered orally.

Experimental: LY3537982 (Dose Expansion) - LY3537982 administered orally either alone or with another investigational agent.

Experimental: LY3537982 (Dose Optimization) - LY3537982 administered orally either alone or with another investigational agent


Treatment: Drugs: LY3537982
Oral

Treatment: Drugs: Pembrolizumab
Intravenous

Treatment: Drugs: Cetuximab
Intravenous

Treatment: Drugs: Pemetrexed
Intravenous

Treatment: Drugs: Cisplatin
Intravenous

Treatment: Drugs: Carboplatin
Intravenous
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1a: To determine the recommended phase 2 dose (RP2D) of LY3537982 monotherapy
Timepoint [1] 0 0
Cycle 1 (21 Days)
Primary outcome [2] 0 0
Phase 1b: To assess the safety and tolerability of LY3537982 when administered alone or in combination with other investigational agents
Timepoint [2] 0 0
Cycle 1 (21 Days)
Primary outcome [3] 0 0
Phase 1b: To determine the optimal dose of LY3537982 to be administered to treatment-naïve participants with advanced NSCLC in combination with pembrolizumab
Timepoint [3] 0 0
Estimated up to 2 years
Primary outcome [4] 0 0
To determine the optimal dose of LY3537982 to be administered to participants who have received at least one prior oxaliplatin- or irinotecan-containing regimen for advanced or metastatic CRC in combination with cetuximab
Timepoint [4] 0 0
Estimated up to 2 years
Primary outcome [5] 0 0
To assess the antitumor activity of LY3537982 monotherapy in participants with advanced pancreatic cancer with KRAS G12C mutation
Timepoint [5] 0 0
Estimated up to 2 years
Secondary outcome [1] 0 0
To assess preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Objective response rate (ORR)
Timepoint [1] 0 0
Estimated up to 2 years
Secondary outcome [2] 0 0
To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Duration of Response (DOR)
Timepoint [2] 0 0
Estimated up to 2 years
Secondary outcome [3] 0 0
To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Best Overall Response (BOR)
Timepoint [3] 0 0
Estimated up to 2 years
Secondary outcome [4] 0 0
To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Time to response (TTR)
Timepoint [4] 0 0
Estimated up to 2 years
Secondary outcome [5] 0 0
To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Disease control rate (DCR)
Timepoint [5] 0 0
Estimated up to 2 years
Secondary outcome [6] 0 0
To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Progression-free survival (PFS)
Timepoint [6] 0 0
Estimated up to 2 years
Secondary outcome [7] 0 0
To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Overall survival (OS)
Timepoint [7] 0 0
Estimated up to 2 years
Secondary outcome [8] 0 0
To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Intracranial DOR based on modified RECIST v1.1 (Certain arms of the study only)
Timepoint [8] 0 0
Estimated up to 2 years
Secondary outcome [9] 0 0
To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Whole-body ORR based on RECIST v1.1 and modified RECIST v1.1 (Certain arms of the study only)
Timepoint [9] 0 0
Estimated up to 2 years
Secondary outcome [10] 0 0
To characterize the pharmacokinetics (PK) properties of LY3537982: Area under the plasma concentration versus time curve (AUC)
Timepoint [10] 0 0
Predose estimated up to 2 years
Secondary outcome [11] 0 0
To characterize the PK properties of LY3537982: Maximum drug concentration (Cmax)
Timepoint [11] 0 0
Predose estimated up to 2 years

Eligibility
Key inclusion criteria
- Patients have measurable disease per Response Evaluation Criteria in Solid Tumors
version 1.1 (RECIST v1.1).

- Patients must have disease with evidence of KRAS G12C mutation in tumor tissue or
circulating tumor deoxyribonucleic acid (DNA).

- Participants must have a histological or a cytologically proven diagnosis of locally
advanced, unresectable, and/or metastatic cancer and meet cohort-specific criteria.

- Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

- Have adequate organ function.

- Have discontinued all previous treatments for cancer with resolution of any
significant ongoing adverse events (AEs), (except in certain scenarios).

- Must be able to swallow capsule/tablet.

- Agree and adhere to contraceptive use, if applicable.

- For some parts of the study, (i.e., one of the two arms with LY3537982 in combination
with pembrolizumab and the arm of LY3537982 in combination with pembrolizumab,
pemetrexed, and platinum therapy) histologically or cytologically confirmed Stage
IIIB-IIIC or Stage IV NSCLC that is previously untreated in the advanced/metastatic
setting and not suitable for curative intent radical surgery or radiation therapy.
Previously untreated patients who received adjuvant and neoadjuvant therapy are
eligible if the last dose of the systemic treatment was completed at least 6 months
prior to enrollment. For untreated patients in the arm with LY3537982 in combination
with pembrolizumab noted above, a single cycle of pembrolizumab may be initiated
within 21 days prior to enrollment. For untreated patients in the arm of LY3537982 in
combination with pembrolizumab, pemetrexed, and platinum therapy, a single cycle of
any or all of the drugs other than LY3537982 may be initiated within 21 days prior to
enrollment. Start of study treatment may be delayed to allow sufficient time for
recovery from treatment-related toxicity.

- For one part of the study, participants must have received at least one prior
oxaliplatin- or irinotecan-containing regimen for advanced or metastatic CRC.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Disease suitable for local therapy administered with curative intent.

- Have an active, ongoing, or untreated infection.

- Have a serious pre-existing medical condition(s) that, in the judgment of the
investigator, would preclude participation in this study.

- Have a serious cardiac condition.

- Have a second active primary malignancy or have been diagnosed and/or treated for an
additional malignancy within 3 years prior to enrollment.

- For some parts of the study only: have untreated active central nervous system (CNS)
metastases and/or leptomeningeal disease. Patients with treated CNS metastases are
eligible for this study if their disease is asymptomatic, radiographically stable for
at least 30 days, and they do not require treatment with steroids in the two-week
period prior to study treatment. Patients with active CNS metastases are eligible for
one part of the study.

- Have received prior treatment with any KRAS G12C small molecule inhibitor, except in
certain scenarios where such prior therapy is allowed as per protocol.

- The following patients will be excluded from some parts of the study:

- Experienced certain serious side effects with prior immunotherapy.

- Have an active autoimmune disease that has required systemic anti-autoimmune
treatment in the past 2 years.

- Have received a live vaccine within 30 days prior to the first dose of study
drug.

- Pregnant, breastfeeding, or expecting to conceive or father children within the
projected duration of the trial through 180 days after the last dose of study
medication.

- Known allergic reaction against any of the components of the study treatments.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/07/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/02/2026
Actual
Sample size
Target
550
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [2] 0 0
St Vincent's Hospital Sydney - Sydney
Recruitment hospital [3] 0 0
Cancer Research SA - Adelaide
Recruitment hospital [4] 0 0
Peninsula and Southeast Oncology - Frankston
Recruitment hospital [5] 0 0
Linear Clinical Research - Nedlands
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment postcode(s) [2] 0 0
2010 - Sydney
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
3199 - Frankston
Recruitment postcode(s) [5] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Louisiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
New Hampshire
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Tennessee
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Utah
Country [15] 0 0
United States of America
State/province [15] 0 0
Virginia
Country [16] 0 0
United States of America
State/province [16] 0 0
Wisconsin
Country [17] 0 0
Canada
State/province [17] 0 0
Alberta
Country [18] 0 0
Canada
State/province [18] 0 0
Ontario
Country [19] 0 0
France
State/province [19] 0 0
Aquitaine
Country [20] 0 0
France
State/province [20] 0 0
Rhône-Alpes
Country [21] 0 0
France
State/province [21] 0 0
Montpellier Cedex 5
Country [22] 0 0
France
State/province [22] 0 0
Paris CEDEX 05
Country [23] 0 0
France
State/province [23] 0 0
Toulouse cedex
Country [24] 0 0
France
State/province [24] 0 0
Villejuif Cedex
Country [25] 0 0
Japan
State/province [25] 0 0
Aichi
Country [26] 0 0
Japan
State/province [26] 0 0
Chiba
Country [27] 0 0
Japan
State/province [27] 0 0
Hokkaido
Country [28] 0 0
Japan
State/province [28] 0 0
Ishikawa
Country [29] 0 0
Japan
State/province [29] 0 0
Tokyo
Country [30] 0 0
Japan
State/province [30] 0 0
Wakayama
Country [31] 0 0
Korea, Republic of
State/province [31] 0 0
Gyeonggi-do
Country [32] 0 0
Korea, Republic of
State/province [32] 0 0
Jeonranamdo
Country [33] 0 0
Korea, Republic of
State/province [33] 0 0
Korea

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Eli Lilly and Company
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Loxo Oncology, Inc.
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Merck Sharp & Dohme LLC
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to find out whether the study drug, LY3537982, is safe and
effective in cancer patients who have a specific genetic mutation (KRAS G12C). Patients must
have already received or were not able to tolerate the standard of care, except for specific
groups who have not had cancer treatment. The study will last up to approximately 4 years.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04956640
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Melinda Willard, PhD
Address 0 0
Loxo Oncology, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Patient Advocacy
Address 0 0
Country 0 0
Phone 0 0
855-569-6305
Fax 0 0
Email 0 0
clinicaltrials@loxooncology.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04956640