A Phase IB/II Study of Alectinib Combined With Cobimetinib in Advanced ALK-Rearranged (ALK+) NSCLC

NCT03202940 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 17-112
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is studying a drug combination as a possible treatment for anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer. The drugs involved in this study are:

• Alectinib
• Cobimetinib

Conditions

Non-small Cell Lung Cancer

Keywords

Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose as assessed by CTCAE v4.0

  The highest dose of the combination of alectinib and cobimetinib that does not cause unacceptable side effects. The maximum tolerated dose is determined in clinical trials by testing increasing doses on different groups of people until the highest dose with acceptable side effects is found.

  28 days

Secondary Outcomes (5)

• The objective response rate, including partial and complete responses, as evaluated by RECIST v1.1

  2 years

• Progression Free Survival as assessed by RECIST v1.1 and the Kaplan-Meier method

  2 years

• Overall Survival as assessed by the Kaplan-Meier method

  2 years

• Safety/Tolerability, or the number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  2 years

• Duration of Response as assessed by RECIST v1.1.

  2 years

Study Arms (1)

Cobimetinib + Alectinib

EXPERIMENTAL

Alectinib administered twice daily at pre-determined dosage orally Cobimetinib administered daily at pre-determined dosage orally

Drug: Alectinib; Drug: Cobimetinib

Interventions

Alectinib DRUG

Alectinib is an oral ALK inhibitor. The term ALK inhibitor means that alectinib targets the abnormal ALK protein that is causing lung cancer cells to grow

Also known as: Alecensa

Cobimetinib + Alectinib

Cobimetinib DRUG

Cobimetinib is an oral inhibitor of MEK, a signaling protein that can cause some types of lung cancer to grow

Also known as: Cotellic

Cobimetinib + Alectinib

Eligibility Criteria

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

You may qualify if:

• Ability to understand and the willingness to sign a written informed consent document.
• Age ≥ 18 years.
• Histologically or cytologically confirmed diagnosis of metastatic NSCLC (Stage IV, AJCC v7.0) that carries an ALK rearrangement, as determined by the Food and Drug Administration (FDA)-approved fluorescence in-situ hybridization (FISH) test, using Vysis® ALK Break apart FISH Probe, or the Ventana® immunohistochemistry (IHC) test. Diagnosis using next generation sequencing (NGS) via a local diagnostic test will be accepted for enrollment but will need to be confirmed with either FISH or IHC.
• For the expansion cohort: Patients must have had disease progression on alectinib (including patients who received alectinib as first-line treatment). Subsequent anti-neoplastic therapy (including other ALK inhibitors or chemotherapy) after progression on alectinib is not permitted. Note: patients in the dose-finding portion of the study may have received other anti-neoplastic therapy after progression on alectinib.
• At least one measurable lesion as defined by RECIST version 1.1. Previously irradiated lesions are not measurable unless the lesion has demonstrated clear progression after radiation.
• Eastern Cooperative Group (ECOG) performance status ≤ 2 for patients treated in the expansion phase. ECOG PS ≤ 1 is required for participants in the dose-finding portion of the study.
• Life expectancy of greater than 12 weeks
• Patient willingness and disease accessible to pre-treatment, on-treatment tumor, and progression biopsies (core biopsies). A cell block from a pleural effusion may be substituted for a core biopsy.
• Able to swallow and retain orally administered medication. Does not have any clinically significant gastrointestinal abnormalities, such as malabsorption syndrome or major resection of the stomach or small bowel that may alter absorption of the medication.
• For participants in the dose-finding phase, a minimum washout period of at least 5 half-lives between the last dose of tyrosine kinase inhibitor (TKI) therapy and the first dose of study treatment is required. For patients on crizotinib, a 7 day washout is sufficient. A shorter washout period may be considered in the event of disease flare, after discussion with the Sponsor. No washout is required if the most recent anti-neoplastic therapy is alectinib.
• Patients must have recovered from treatment toxicities to ≤ Grade 1 or to their pretreatment levels except for adverse events (AEs) that in the investigator's judgment do not constitute a safety risk for the patient.
• Patients can either be chemotherapy-naive or have received platinum-based chemotherapy for locally advanced or metastatic disease. Acute effects of therapy must have resolved to baseline severity or to CTCAE grade ≤1 except for AEs that in the investigator's judgment do not constitute a safety risk for the patient. Patients who have received prior treatment with checkpoint inhibitors are eligible.
• Recovery from effects of any major surgery or significant traumatic injury at least 28 days before the first dose of study treatment
• For all women of childbearing potential, a negative pregnancy test must be obtained at the baseline visit before starting study treatment. For women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use two adequate methods of contraception, including at least one method with a failure rate of \< 1% per year, during the treatment period and for at least 90 days after the last dose of study drug.
• Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception.

You may not qualify if:

• Participants who have had chemotherapy within 3 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier.
• Participants who experienced progression of CNS lesions on alectinib who have not received local CNS therapies (radiation, surgery) to address the lesions. CNS imaging obtained at least 21 days after completion of radiation is required for confirmation of response.
• Radiation therapy (except palliative to relieve bone pain) within 7 days of study entry. Palliative radiation (≤ 10 fractions) must have been completed at least 48 hours prior to study entry. Stereotactic or small field brain irradiation must have been completed at least 7 days prior to study entry. Whole brain radiation and radiation for leptomeningeal metastasis must have been completed at least 2 weeks prior to study entry. Acute effects of radiation must have resolved to baseline severity or to CTCAE grade ≤1 except for AEs that in the investigator's judgment do not constitute a safety risk for the patient.
• Participants with uncontrolled tumor-related pain.
• Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should be treated prior to enrollment.
• Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastases that are not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment.
• Patients who are receiving denosumab prior to enrollment who are not willing and/or eligible to switch to a bisphosphonate while on study.
• Pregnant or lactating women.
• History of hypersensitivity to alectinib or any of its excipients. In addition, subjects who are unable to tolerate the 600 mg twice daily (BID) dose of alectinib will not be permitted to enroll unless doses of alectinib below the entry level are being investigated (e.g. dose level -1 and -2) and they have previously tolerated alectinib monotherapy at the dose being investigated.
• Participants with prior allogeneic stem cell or solid organ transplantation.
• History of extensive, disseminated, bilateral or presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease including pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis or pulmonary fibrosis. Patients with history of prior radiation pneumonitis are not excluded.
• Serum albumin \< 2.5 g/dL
• Positive test for human immunodeficiency virus (HIV) or history of active tuberculosis
• Current use or anticipated need for food or drugs that are known strong or moderate CYP3A4 inhibitors, including their administration within 2 weeks prior to the first study treatment (ie, strong CYP3A4 inhibitors: grapefruit juice or grapefruit/grapefruit related citrus fruits \[eg, Seville oranges, pomelos\], ketoconazole, miconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, amprenavir, fosamprenavir nefazodone, lopinavir, troleandomycin, mibefradil, and conivaptan; Moderate CYP3A4 inhibitors: erythromycin, verapamil, atazanavir, delavirdine, fluconazole, darunavir, diltiazem, aprepitant, imatinib, tofisopam, ciprofloxacin, cimetidine). For participants in the dose escalation portion, no CYP3A4 inhibitors should be administered during the first 21 days of the study, regardless of strength.
• Current use or anticipated need for drugs that are known strong or moderate CYP3A4 inducers including their administration within 2 weeks prior to the first study treatment (ie, phenobarbital, rifampin, phenytoin, carbamazepine, rifabutin, rifapentin, clevidipine, St. John's Wort). For participants in the dose escalation portion, no CYP3A4 inducers should be administered during the first 21 days of the study, regardless of strength.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Massachusetts general Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

alectinib; cobimetinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Ibiayi T Dagogo-Jack, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 12, 2017
• First Posted: June 29, 2017
• Study Start: September 14, 2017
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2031
• Last Updated: September 25, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)