Study of XL092 + Atezolizumab vs Regorafenib in Subjects With Metastatic Colorectal Cancer (STELLAR-303)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Exelixis Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

22 Dec 2022 → ongoing

Decision date (initial)

2024-07-31

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Exelixis, Inc.

External identifiers

EU CT number

2024-512915-33-00

EudraCT number

2021-003243-21

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy

1. To evaluate the overall survival of XL092 + atezolizumab versus regorafenib in all randomized subjects with MSS/MSI-low mCRC who hav progressed during, after, or are intolerant to SOC therapy.
2. To evaluate the overall survival of XL092 + atezolizumab versus regorafenib in NLM subjects with MSS/MSI-low mCRC who have progressed during, after, or are intolerant to SOC therapy

Secondary objectives 4

1. To evaluate the efficacy of XL092 + atezolizumab versus regorafenib in all randomized subjects with MSS/MSI-low mCRC who have progressed during, after, or are intolerant to SOC therapy.
2. To evaluate the efficacy of XL092 + atezolizumab versus regorafenib in randomized NLM subjects with MSS/MSI-low mCRC who have progressed during, after, or are intolerant to SOC therapy.
3. To assess safety and tolerability of XL092 + atezolizumab versus regorafenib in all randomized subjects with MSS/MSI-low mCRC who have progressed during, after, or are intolerant to SOC therapy.
4. To characterize PK of XL092, its potential metabolites, and atezolizumab, and immunogenicity of atezolizumab in randomized subjects given XL092 in combination with atezolizumab with MSS/MSI-low mCRC who have progressed during, after, or are intolerant to SOC therapy.

Conditions and MedDRA coding

Metastatic Colorectal Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Subjects with histologically or cytologically confirmed adenocarcinoma of the colon or rectum
2. Has received the following SOC anticancer therapies as prior therapy for metastatic CRC and has radiographically progressed, is refractory or intolerant to these therapies. Prior investigational therapies are allowed.
3. Measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1; Eisenhauer et al 2009) as determined by the Investigator.
4. Available archival tumor biopsy material. If archival tissue is unavailable, must provide fresh tumor tissue biopsy prior to randomization.
5. Recovery to baseline or ≤ Grade 1 severity (CTCAE v5) from AEs related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy
6. Age 18 years or older on the day of consent.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
8. Adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 10 days before randomization.
9. Capable of understanding and complying with the protocol requirements and must have signed the informed consent document.
10. Fertile subjects and their partners must agree to use highly effective methods of contraception (defined in Appendix H) during the course of the study and for the following durations after the last dose of treatment (whichever is later)
11. Female subjects of childbearing potential must not be pregnant at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria is met: permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of consecutive amenorrhea in a female > 45 years-of-age in the absence of other biological or physiological causes. In addition, females < 55 years-of-age must have a serum follicle-stimulating hormone [FSH] level > 40 mIU/mL to confirm menopause).

Exclusion criteria 15

1. Prior treatment with XL092, regorafenib, trifluridine/tipiracil, or PD-L1/PD-1 targeting ICIs.
2. Receipt of a small molecule kinase inhibitor (including investigational agents) within 2 weeks before randomization.
3. Receipt of any type of anticancer antibody therapy, systemic chemotherapy, or hormonal anticancer therapy within 3 weeks (or bevacizumab within 4 weeks) before randomization.
4. Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before randomization. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
5. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before randomization.
6. The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions: (please refer to the protocol)
7. Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 4 weeks prior to randomization. Complete wound healing from major or minor surgery must have occurred at least prior to randomization.
8. Systemic treatment with, or any condition requiring, either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to randomization.
9. Corrected QT interval calculated by the Fridericia formula (QTcF) > 460 ms within 10 days before randomization per electrocardiogram (ECG) before randomization (see Section 5.7.4 for Fridericia formula).
10. History of psychiatric illness likely to interfere with ability to comply with protocol requirements or give informed consent.
11. Pregnant or lactating females.
12. Inability to swallow study treatment formulation, inability to receive IV administration, or presence of GI condition that might affect the absorption of study drug (eg, PEG tube).
13. Previously identified allergy or hypersensitivity to components of the study treatment formulations.
14. Any other active malignancy or diagnosis of another malignancy within 2 years before randomization, except for superficial skin cancers, or localized, low-grade tumors deemed cured and not treated with systemic therapy. Incidentally diagnosed prostate cancer is allowed if assessed as stage ≤ T2N0M0 and Gleason score ≤ 6.
15. Administration of a live, attenuated vaccine within 30 days before randomization.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall Survival

Secondary endpoints 3

1. PFS as assessed by the investigator per RECIST 1.1, ORR as assessed by the investigator per RECIST 1.1, DOR as assessed by the investigator per RECIST 1.1
2. Incidence and severity of Es, SAEs and adverse events of special interest (AESIs)
3. Plasma concentration of XL092 given in combination with atezolizumab, serum concentration of atezolizumab given in combination with XL092, the incidence of antidrug antibody (ADA) response against atezolizumab given in combination with XL092.

Investigational products

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

Test 4

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Exelixis Inc.

Sponsor organisation

Exelixis Inc.

Address

1851 Harbor Bay Parkway

City

Alameda

Postcode

94502-3010

Country

United States

Scientific contact point

Organisation

Exelixis Inc.

Contact name

Exelixis, Inc.

Public contact point

Organisation

Exelixis Inc.

Contact name

Exelixis, Inc.

Third parties 17

Locations

7 EU/EEA countries · 37 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 74 files

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

Application history

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