A Study to Evaluate the Safety, Pharmacokinetics, and Activity of GDC-6036 Alone or in Combination in Participants With Advanced or Metastatic Solid Tumors With a KRAS G12C Mutation

Sponsor

Genentech, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04449874

Collaborator

(none)

498

Enrollment

Locations

Arms

36.1

Anticipated Duration (Months)

8.6

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase I dose-escalation and dose-expansion study that will evaluate the safety, pharmacokinetics (PK), and preliminary activity of GDC-6036 in patients with advanced or metastatic solid tumors with a KRAS G12C mutation.

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Cancer Colorectal Cancer Advanced Solid Tumors	Drug: GDC-6036 Drug: Atezolizumab Drug: Cetuximab Drug: Bevacizumab Drug: Erlotinib Drug: GDC-1971 Drug: Inavolisib	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

498 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase Ia/Ib Dose-Escalation and Dose-Expansion Study Evaluating the Safety, Pharmacokinetics, and Activity of GDC-6036 as a Single Agent and in Combination With Other Anti-cancer Therapies in Patients With Advanced or Metastatic Solid Tumors With a KRAS G12C Mutation

Actual Study Start Date :

Jul 29, 2020

Anticipated Primary Completion Date :

Aug 2, 2023

Anticipated Study Completion Date :

Aug 2, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A: Dose-escalation (Stage I), Dose Expansion (Stage II) Participants in Stage I will receive GDC-6036 administered orally once daily (PO QD). The dose will be increased in successive cohorts until a study-specific threshold is reached. Participants with select solid tumors will be treated with GDC-6036 PO QD in Stage II.	Drug: GDC-6036 The starting dose of GDC-6036 in the combination Arms B, C, D, E, F and G will be determined from Stage I Arm A (single-agent dose escalation).
Experimental: Arm B: GDC-6036 + Atezolizumab (Stage I and Stage II) Participants with non-small cell lung cancer will receive GDC-6036 in combination with atezolizumab.	Drug: GDC-6036 The starting dose of GDC-6036 in the combination Arms B, C, D, E, F and G will be determined from Stage I Arm A (single-agent dose escalation). Drug: Atezolizumab A 1200 milligram (mg) intravenous (IV) infusion of atezolizumab will be administered on Day 1 of 21 day cycles.
Experimental: Arm C: GDC-6036 + Cetuximab (Stage I and Stage II) Participants with colorectal cancer will receive GDC-6036 in combination with cetuximab.	Drug: GDC-6036 The starting dose of GDC-6036 in the combination Arms B, C, D, E, F and G will be determined from Stage I Arm A (single-agent dose escalation). Drug: Cetuximab Cetuximab will be administered at an initial dose of 400 milligram per square meter (mg/m^2) IV infusion followed by 250 mg/m^2 IV infusion weekly in 21 day cycles.
Experimental: Arm D: GDC-6036 + Bevacizumab (Stage I and Stage II) Participants with solid tumors will receive GDC-6036 in combination with bevacizumab.	Drug: GDC-6036 The starting dose of GDC-6036 in the combination Arms B, C, D, E, F and G will be determined from Stage I Arm A (single-agent dose escalation). Drug: Bevacizumab A 15 milligram per kilogram (mg/kg) IV infusion of bevacizumab will be administered on Day 1 of 21 day cycles.
Experimental: Arm E: GDC-6036 + Erlotinib (Stage I and Stage II) Participants with non-small cell lung cancer will receive GDC-6036 in combination with erlotinib.	Drug: GDC-6036 The starting dose of GDC-6036 in the combination Arms B, C, D, E, F and G will be determined from Stage I Arm A (single-agent dose escalation). Drug: Erlotinib 150 mg of erlotinib will be administered PO QD in 21 day cycles.
Experimental: Arm F: GDC-6036 + GDC-1971 (Stage I and Stage II) Participants with solid tumors will receive GDC-6036 in combination with GDC-1971 PO in Stage I. Participants with select solid tumors will be treated with GDC-6036 in combination with GDC-1971 PO in Stage II.	Drug: GDC-6036 The starting dose of GDC-6036 in the combination Arms B, C, D, E, F and G will be determined from Stage I Arm A (single-agent dose escalation). Drug: GDC-1971 The starting dose of GDC-1971 will be determined from its single-agent dose escalation.
Experimental: Arm G: GDC-6036 + Inavolisib (Stage I and Stage II) Participants with solid tumors will receive GDC-6036 in combination with inavolisib PO in Stage I. Participants with select solid tumors will be treated with GDC-6036 in combination with inavolisib PO in Stage II.	Drug: GDC-6036 The starting dose of GDC-6036 in the combination Arms B, C, D, E, F and G will be determined from Stage I Arm A (single-agent dose escalation). Drug: Inavolisib The starting dose of inavolisib will be determined from its single-agent dose escalation.

Outcome Measures

Primary Outcome Measures

Percentage of Participants With Adverse Events (AEs) [From Cycle 1 Day 1 until 28 days after the final dose (or as specified in the protocol). A cycle is 21 days.]
Severity is determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
Percentage of Participants With Dose-Limiting Toxicities (DLTs) [From Cycle 1 Day 1 through Day 21. A cycle is 21 days.]

Secondary Outcome Measures

Plasma Concentrations of GDC-6036 [Various timepoints from Cycle 1 Day 1 through study treatment discontinuation (within 28 days after the final dose of study drug). A cycle is 21 days.]
Plasma Concentrations of Erlotinib [Various timepoints from Cycle 1 Day 1 through study treatment discontinuation (within 28 days after the final dose of study drug). A cycle is 21 days.]
Plasma Concentrations of GDC-1971 [Various timepoints from Cycle 1 Day 1 through study treatment discontinuation (within 28 days after the final dose of study drug). A cycle is 21 days.]
Plasma Concentrations of Inavolisib [Various timepoints from Cycle 1 Day 1 through study treatment discontinuation (within 28 days after the final dose of study drug). A cycle is 21 days.]
Objective Response Rate (ORR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) [Every 6 weeks from Cycle 1 Day 1 until study treatment discontinuation (within 28 days after the final dose of study drug). A cycle is 21 days.]
Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1 [Every 6 weeks from Cycle 1 Day 1 until study treatment discontinuation (within 28 days after the final dose of study drug). A cycle is 21 days.]
Progression-free survival (PFS) as determined by the investigator according to RECIST v1.1 [Every 6 weeks from Cycle 1 Day 1 until study treatment discontinuation (within 28 days after the final dose of study drug). A cycle is 21 days.]
Relationship Between GDC-6036 Exposure (Maximum Plasma Concentration Observed [Cmax]) [Various timepoints from Cycle 1 Day 1 through study treatment discontinuation (within 28 days after the final dose of study drug). A cycle is 21 days.]
Relationship Between GDC-6036 Exposure (Time to Maximum Plasma Concentration [Tmax]) [Various timepoints from Cycle 1 Day 1 through study treatment discontinuation (within 28 days after the final dose of study drug). A cycle is 21 days.]
Relationship Between GDC-6036 Exposure (Half-life [t1/2]) [Various timepoints from Cycle 1 Day 1 through study treatment discontinuation (within 28 days after the final dose of study drug). A cycle is 21 days.]
Relationship Between GDC-6036 Exposure (Area Under the Curve [AUC]) [Various timepoints from Cycle 1 Day 1 through study treatment discontinuation (within 28 days after the final dose of study drug). A cycle is 21 days.]
Relationship Between Tumor Pharmacodynamic Effects of GDC-6036 [Various timepoints from Cycle 1 Day 1 through study treatment discontinuation (within 28 days after the final dose of study drug). A cycle is 21 days.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically documented advanced or metastatic solid tumor with KRAS G12C mutation.
Women of childbearing potential must agree to remain abstinent or use contraception, and agree to refrain from donating eggs during the treatment period and after the final dose of study treatment as specified in the protocol.
Men who are not surgically sterile must agree to remain abstinent or use a condom, and agreement to refrain from donating sperm during the treatment period and after the final dose of study treatment as specified in the protocol.

Exclusion Criteria:

Active brain metastases.
Malabsorption or other condition that interferes with enteral absorption.
Clinically significant cardiovascular dysfunction or liver disease.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
2	UCSD Moores Cancer Center	La Jolla	California	United States	92093
3	Chao Family Comprehensive Cancer Center UCI	Orange	California	United States	92868
4	Univ of Calif, San Francisco; Breast Cancer Center	San Francisco	California	United States	94115
5	Yale Cancer Center	New Haven	Connecticut	United States	06520
6	Florida Cancer Specialists - Sarasota	Sarasota	Florida	United States	34232
7	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
8	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
9	University of Oklahoma; Stephenson Oklahoma Canc Ctr	Oklahoma City	Oklahoma	United States	73104
10	Abramson Cancer Center; Univ of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
11	UPMC - Hillman Cancer Center	Pittsburgh	Pennsylvania	United States	15232
12	St Vincent's Hospital Sydney	Darlinghurst	New South Wales	Australia	2010
13	Alfred Health	Melbourne	Victoria	Australia	3004
14	Peter MacCallum Cancer Center	North Melbourne	Victoria	Australia	3051
15	Linear Clinical Research Limited	Nedlands	Western Australia	Australia	6009
16	UZ Antwerpen	Edegem		Belgium	2650
17	CHU de Liège	Herstal		Belgium	4040
18	AZ St Maarten Campus Leopoldstr	Mechelen		Belgium	2800
19	Ottawa Hospital	Ottawa	Ontario	Canada	K1H 8L6
20	Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M5G 1Z5
21	Jewish General Hospital; Sir Mortimer B. Davis	Montreal	Quebec	Canada	H2W 1S6
22	Rambam Medical Center	Haifa		Israel	3109601
23	Sheba Medical Center - PPDS	Ramat-Gan		Israel	5262000
24	Tel-Aviv Sourasky Medical Center	Tel Aviv		Israel	6423906
25	Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST - PPDS	Meldola	Emilia-Romagna	Italy	47014
26	Irccs Ospedale San Raffaele;Oncologia Medica	Milano	Lombardia	Italy	20132
27	Asst Grande Ospedale Metropolitano Niguarda	Milano	Lombardia	Italy	20162
28	Istituto Clinico Humanitas	Rozzano (MI)	Lombardia	Italy	20089
29	Azienda Ospedaliero Universitaria Pisana	Pisa	Toscana	Italy	56100
30	Seoul National University Bundang Hospital	Seongnam-si		Korea, Republic of	13605
31	Seoul National University Hospital	Seoul		Korea, Republic of	03080
32	Asan Medical Center - PPDS	Seoul		Korea, Republic of	05505
33	Samsung Medical Center - PPDS	Seoul		Korea, Republic of	06351
34	Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis	Amsterdam		Netherlands	1066 CX
35	Leids Universitair Medisch Centrum	Leiden		Netherlands	2333 ZA
36	Maastricht University Medical Center	Maastricht		Netherlands	6229 HX
37	Universitair Medisch Centrum Utrecht	Utrecht		Netherlands	3584 CX
38	Auckland City Hospital	Auckland		New Zealand	1023
39	New Zealand Clinical Research - Christchurch	Christchurch		New Zealand	8011
40	Oslo university hospital Radiumhospitalet	Oslo		Norway	0424
41	Medical University of Gdansk	Gdansk		Poland	80-952
42	Biokinetica, Przychodnia Jozefow	Jozefow		Poland	05-410
43	Szpital Kliniczny im. Heliodora Święcickiego UM w Poznaniu.	Poznań		Poland	60-780
44	Republican Clinical Oncology Dispensary of Ministry of Healthcare of Tatarstan Republic	Kazan	Tatarstan	Russian Federation	420029
45	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
46	START Madrid-FJD, Hospital Fundacion Jimenez Diaz	Madrid		Spain	28040
47	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
48	Hospital Universitario HM Sanchinarro-CIOCC	Madrid		Spain	28050
49	Hospital Clinico Universitario Virgen de la Victoria	Malaga		Spain	29010
50	Hospital Universitario Virgen del Rocío	Sevilla		Spain	41013
51	Hospital Clinico Universitario de Valencia	Valencia		Spain	46010
52	Universitaetsspital Basel; Onkologie	Basel		Switzerland	4031
53	Inselspital	Bern		Switzerland	3010
54	Hôpitaux Universitaires de Genève	Genève		Switzerland	1211
55	Unversitätsspital Zürich	Zürich		Switzerland	8091
56	Velindre Cancer Centre	Cardiff		United Kingdom	CF14 2TL
57	University College London Hospitals NHS Foundation Trust; NIHR UCLH Clinical Research Facility	London		United Kingdom	W1T 7HA
58	The Christie NHS Foundation Trust	Manchester		United Kingdom	M20 4BX