Clinical trial NCT05954871: Study to Evaluate the Safety, Pharmacokinetics, and Activity of GDC-1971 in Combination With Either Osimertinib in Participants With Unresectable, Locally Advanced, or Metastatic Non-Small Cell Lung Cancer, or With Cetuximab in Participants With Metastatic Colorectal Cancer
Official title: A Phase Ib Study to Evaluate the Safety, Pharmacokinetics, and Activity of GDC-1971 in Combination With Either Osimertinib in Patients With Unresectable, Locally Advanced, or Metastatic Non-Small Cell Lung Cancer, or With Cetuximab in Patients With Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Colorectal Cancer
Non-Small Cell Lung Cancer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2023-07-20
Enrollment: 172
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The main purpose of the study is to evaluate the safety of GDC-1971 in combination with either osimertinib or cetuximab. The study consists of a dose-finding stage followed by an expansion stage.


Eligibility criteria: Inclusion Criteria:

* Evaluable or measurable disease per RECIST v1.1
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Life expectancy of ≥12 weeks
* Adequate hematologic and organ function within 14 days prior to initiation of study Inclusion Criteria for Non-Small Cell Lung Cancer Cohorts
* Histologically confirmed unresectable, locally advanced or metastatic adenocarcinoma of the lung that has progressed on/after prior treatment with third-generation epidermal growth factor receptor (EGFR) inhibitor (e.g., osimertinib)
* Positive for an EGFR exon 19 deletion or exon 21 L858R mutation
* Negative for acquired on-target EGFR alterations Inclusion Criteria for Colorectal Cancer Cohorts
* Histologically confirmed metastatic adenocarcinoma of the colon or rectum that has progressed on/after prior treatment with an EGFR inhibitor (e.g., cetuximab or panitumumab)
* Negative for kirsten rat sarcoma viral oncogene homolog (KRAS) alterations
* Negative for neuroblastoma RAS viral oncogene homolog (NRAS) alterations
* Negative for proto-oncogene B-Raf (BRAF) V600E alterations
* In lieu of a fresh pre-treatment biopsy, a recently obtained biopsy performed after completion of osimertinib therapy will be acceptable

Exclusion Criteria:

* Treatment with chemotherapy, immunotherapy, biologic therapy, or an investigational agent as anti-cancer therapy within 3 weeks or 5 drug elimination half-lives, whichever is shorter, prior to initiation of study treatment
* Treatment with endocrine therapy within 2 weeks prior to initiation of study drug, except for hormonal therapy with gonadotropin-releasing hormone agonists or antagonists for endocrine-sensitive cancers
* Significant traumatic injury or major surgical procedure within 4 weeks prior to Cycle 1, Day 1
* Positive hepatitis C virus (HCV) antibody test at screening
* Positive hepatitis B surface antigen (HBsAg) test at screening
* Known HIV infection
* Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
* Uncontrolled hypercalcemia
* Substance abuse, as determined by the investigator, within 12 months prior to screening
* Poor peripheral venous access
* Inability or unwillingness to swallow pills
* Malabsorption syndrome or other condition that would interfere with enteral absorption Chronic diarrhea, short bowel syndrome, or significant upper GI surgery including gastric resection, a history of inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis), or any active bowel inflammation (including diverticulitis)
* Serious infection within 4 weeks prior to screening
* History of malignancy within 3 years prior to screening
* Known and untreated, or active central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control)
* Leptomeningeal disease or carcinomatous meningitis
* History or presence of an abnormal electrocardiogram (ECG) that is deemed clinically significant by the investigator (e.g., complete left bundle branch block, second- or third-degree atrioventricular heart block) or evidence of prior myocardial infarction
* Left ventricular ejection fraction (LVEF) less than the institutional lower limit of normal (LLN) or \<50%
* History or evidence of ophthalmic disease
* History of or active clinically significant cardiovascular dysfunction
* History of pulmonary firbrosis, organizing pneumonia, or pneumonitis

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Percentage of Participants with Adverse Events (AEs) Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
timeFrame: Up to approximately 41 months
measure: Number of Participants with Dose-Limiting Toxicities (DLTs)
timeFrame: Day 1 through Day 28 of Cycle 1 (1cycle= 28 days)
Secondary outcomes:
measure: Plasma Concentration of GDC-1971
timeFrame: Up to approximately 41 months
measure: Plasma Concentration of Osimertinib
timeFrame: Up to approximately 41 months
measure: Objective Response Rate (ORR) as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).
timeFrame: Up to approximately 41 months
measure: Duration of Response (DOR) as Determined by Investigator According to RECIST v1.1
timeFrame: Up to approximately 41 months
measure: Progression-Free Survival (PFS) After Enrollment as Determined by Investigator According to RECIST v1.1
timeFrame: Up to approximately 41 months
Other outcomes:
Locations:
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: San Antonio
country: United States
facility: START South Texas Accelerated Research Therapeutics-San Antonio
state: Texas
city: Wodonga
country: Australia
facility: Border Medical Oncology
state: New South Wales
city: Fitzroy
country: Australia
facility: St Vincent's Hospital Melbourne
state: Victoria
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: