DESC:The following specification particularly describes the invention and the manner in
which it is to be performed.

NOVEL CRYSTALLINE FORMS OF ADAGRASIB

FIELD OF THE INVENTION

The present application relates to crystalline forms DRC1, DRC2 and DRC3 of adagrasib, their preparative methods and pharmaceutical compositions thereof.

BACKGROUND OF THE INVENTION
Adagrasib is a KRAS inhibitor being developed by Mirati Therapeutics. It was approved in US under the brand name KRAZATI for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) as determined by an FDA approved test, who have received at least one prior systemic therapy. Adagrasib is chemically known as {(2S)-4-[7-(8-chloronaphthalen-1-yl)-2-{[(2S)-1- methylpyrrolidin-2-yl]methoxy}-5,6,7,8- tetrahydropyrido[3,4-d]pyrimidin-4-yl]-1-(2-fluoroprop2-enoyl)piperazin-2-yl}acetonitrile and has following structural formula:

(I)
Adagrasib was first disclosed in WO2019099524A1 (hereinafter referred as the WO’524 application) assigned to Mirati Therapeutics. WO2022056307A1 (hereinafter referred as the WO’307 application) discloses crystalline forms A, B, C, D and E of adagrasib. CN 113429405A (hereinafter referred as the CN’ 405 application) discloses crystalline form DCI of adagrasib. CN113527294A (hereinafter referred as the CN’ 294 application) discloses crystalline form DCIII of adagrasib. CN115521312A (hereinafter referred as the CN’ 312 application) discloses XM1 to XM5 of adagrasib.
New polymorphic forms, solvates and solid dispersions of a pharmaceutically useful compound or salts thereof can also provide an opportunity to improve the performance characteristics of a pharmaceutical product. It enlarges the repertoire of materials that a formulation scientist has available for formulation optimization, for example by providing a product with different properties, e.g., better processing or handling characteristics, improved dissolution profile, or improved shelf-life. For at least these reasons, there is a need for additional solid forms of adagrasib.

SUMMARY OF THE INVENTION
First aspect of the present application relates to crystalline form DRC1 of Adagrasib characterized by one or more peaks selected from its powder X-ray diffraction (PXRD) pattern having peaks at about 6.5, 8.6, 11.2, 12.9, 14.6, 16.0, 16.7, 16.9, 17.9, 18.1, 19.9, 20.1, 21.2, 21.5, 22.9, 23.5, 24.1, 24.5, 24.8, 25.4, 26.2, 26.6, 27.3, 27.9, 28.5, 29.0, 30.4, 31.3, 31.7, 31.9, 32.6, 33.5, 34.0, 34.5, 34.9, 35.3, 37.1, 37.8, 39.5 ± 0.2 2?.
Second aspect of the present application relates to crystalline form DRC1 of Adagrasib characterized by a PXRD pattern substantially as illustrated in Figure 1.

Third aspect of the present application relates to a process for preparing crystalline form DRC1 of Adagrasib; the process comprising;
a) providing a slurry or suspension comprising Adagrasib and Aspartame by mixing Adagrasib with Aspartame in presence of a solvent;
b) isolating crystalline form DRC1 of Adagrasib from the mixture of step a); and;
c) optionally, drying the isolated product at suitable temperature.

Fourth aspect, the present application provides a pharmaceutical composition comprising crystalline form DRC1 of Adagrasib and at least one pharmaceutically acceptable carrier.

Fifth aspect of the present application relates to crystalline form DRC2 of Adagrasib characterized by one or more peaks selected from its powder X-ray diffraction (PXRD) pattern having peaks at about 5.0, 6.4, 6.9, 8.2, 9.2, 10.0, 10.3, 10.6, 12.1, 12.3, 13.2, 13.6, 14.1, 14.3, 14.7, 15.3, 16.1, 16.4, 16.7, 17.3, 17.9, 18.3, 18.5, 19.5, 19.9, 20.2, 21.1, 21.3, 21.6, 22.4, 22.6, 23.6, 23.9, 24.9, 25.7, 25.9, 26.3, 27.1, 27.8, 28.5, 29.1, 30.3, 31.4, 32.5, 33.6, 34.5, 35.4, 37.6, 37.9, 39.2 ± 0.2° 2?.

Sixth aspect of the present application relates to crystalline form DRC2 of Adagrasib characterized by a PXRD pattern substantially as illustrated in Figure 2.

Seventh aspect of the present application relates to a process for preparing crystalline form DRC2 of Adagrasib; the process comprising;
a) providing a slurry or a suspension comprising Adagrasib and ß-Cyclodextrin by mixing Adagrasib with ß-Cyclodextrin in presence of a solvent;
b) isolating crystalline form DRC2 of Adagrasib from the mixture of step a); and;
c) optionally, drying the isolated product at suitable temperature.

Eighth aspect, the present application provides a pharmaceutical composition comprising crystalline form DRC2 of Adagrasib and at least one pharmaceutically acceptable carrier.

Ninth aspect of the present application relates to crystalline form DRC3 of Adagrasib characterized by one or more peaks selected from its powder X-ray diffraction (PXRD) pattern having peaks at about 3.7, 7.1, 8.6, 9.2, 10.1, 10.9, 11.3, 12.1, 12.7, 13.1, 13.8, 14.2, 14.8, 15.1, 15.6, 16.7, 17.1, 17.4, 17.8, 18.6, 19.1, 19.4, 20.2, 20.5, 20.9, 21.6, 22.0, 22.3, 22.8, 23.2, 23.6, 24.2, 25.1, 25.4, 26.2, 26.8, 27.9, 28.2, 29.0, 30.3, 30.8, 32.1, 32.9, 33.4, 33.9, 34.7, 35.8, 37.6, 38.9 ± 0.2° 2?.

Tenth aspect of the present application relates to crystalline form DRC3 of Adagrasib characterized by a PXRD pattern substantially as illustrated in Figure 3.

Eleventh aspect of the present application relates to a process for preparing crystalline form DRC3 of Adagrasib; the process comprising;
a) providing a slurry or a suspension comprising Adagrasib and pamoic acid by mixing Adagrasib with pamoic acid optionally in presence of a solvent;
b) isolating crystalline form DRC3 of Adagrasib from the mixture of step a); and;
c) optionally, drying the isolated product at suitable temperature.

Twelfth, aspect, the present application provides a pharmaceutical composition comprising crystalline form DRC3 of Adagrasib and at least one pharmaceutically acceptable carrier.

BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 is powder X-ray diffraction ("PXRD") pattern of crystalline from DRC1 of Adagrasib.
Figure 2 is powder X-ray diffraction ("PXRD") pattern of crystalline from DRC2 of Adagrasib.
Figure 3 is powder X-ray diffraction ("PXRD") pattern of crystalline from DRC3 of Adagrasib.

DETAILED DESCRITPION
First aspect of the present application relates to crystalline form DRC1 of Adagrasib characterized by one or more peaks selected from its powder X-ray diffraction (PXRD) pattern having peaks at about 6.5, 8.6, 11.2, 12.9, 14.6, 16.0, 16.7, 16.9, 17.9, 18.1, 19.9, 20.1, 21.2, 21.5, 22.9, 23.5, 24.1, 24.5, 24.8, 25.4, 26.2, 26.6, 27.3, 27.9, 28.5, 29.0, 30.4, 31.3, 31.7, 31.9, 32.6, 33.5, 34.0, 34.5, 34.9, 35.3, 37.1, 37.8, 39.5 ± 0.2 2?.
Second aspect of the present application relates to crystalline form DRC1 of Adagrasib characterized by a PXRD pattern substantially as illustrated in Figure 1.

Third aspect of the present application relates to a process for preparing crystalline form DRC1 of Adagrasib; the process comprising;
a) providing a slurry or suspension comprising Adagrasib and Aspartame by mixing Adagrasib with Aspartame in presence of a solvent;
b) isolating crystalline form DRC1 of Adagrasib from the mixture of step a); and;
c) optionally, drying the isolated product at suitable temperature.

In embodiments of step a), the solvent may include but not limited to, alcohols such as methanol, isopropanol and the like; ketones such as acetone, methyl isobutyl ketone and the like; ethers such as diethyl ether, tetrahydrofuran and the like; esters such as ethyl acetate, propyl acetate and the like; water; mixture thereof. Preferably solvent is a mixture of alcohol and ketone solvent. More preferably, solvent is a mixture of isopropyl alcohol and acetone.

In one of the embodiments of step a), any physical form of Adagrasib may be utilized, which may be crystalline or amorphous, for providing the suspension of Adagrasib in a solvent comprising Aspartame. In another embodiment of step a), any physical form of Adagrasib may be utilized, which may be anhydrous or hydrate or solvate for providing the suspension of Adagrasib in a solvent comprising Aspartame.
Isolation of crystalline form DRC1 of Adagrasib in step b) may be performed by any technique known in the art. Specifically, crystalline form DRC1 of Adagrasib may be isolated from the mixture of step a) by filtration followed by drying.
The resulting compound obtained in step (b) may optionally be further dried. Drying can be carried out in a tray dryer, vacuum oven, air oven, cone vacuum dryer, rotary vacuum dryer, fluidized bed dryer, spin flash dryer, flash dryer, or the like. The drying can be carried out at temperatures between RT to 75 °C or at a temperature of about 50 °C or any other suitable temperatures; at atmospheric pressure or under a reduced pressure; as long as the Adagrasib is not degraded in its quality. The drying can be carried out for any desired time until the required product quality is achieved. Suitable time for drying can vary from few minutes to several hours for example from about 30 minutes to about 24 or more hours.

Fourth aspect of the present application relates to a pharmaceutical composition comprising crystalline form DRC1 of Adagrasib and one or more pharmaceutically acceptable excipient.

Fifth aspect of the present application relates to crystalline form DRC2 of Adagrasib characterized by one or more peaks selected from its powder X-ray diffraction (PXRD) pattern having peaks at about 5.0, 6.4, 6.9, 8.2, 9.2, 10.0, 10.3, 10.6, 12.1, 12.3, 13.2, 13.6, 14.1, 14.3, 14.7, 15.3, 16.1, 16.4, 16.7, 17.3, 17.9, 18.3, 18.5, 19.5, 19.9, 20.2, 21.1, 21.3, 21.6, 22.4, 22.6, 23.6, 23.9, 24.9, 25.7, 25.9, 26.3, 27.1, 27.8, 28.5, 29.1, 30.3, 31.4, 32.5, 33.6, 34.5, 35.4, 37.6, 37.9, 39.2 ± 0.2° 2?.

Sixth aspect of the present application relates to crystalline form DRC2 of Adagrasib characterized by a PXRD pattern substantially as illustrated in Figure 2.

Seventh aspect of the present application relates to a process for preparing crystalline form DRC2 of Adagrasib; the process comprising;
a) providing a slurry or a suspension comprising Adagrasib and betacyclodextrin by mixing Adagrasib with betacyclodextrin in presence of a solvent;
b) isolating crystalline form DRC2 of Adagrasib from the mixture of step a); and;
c) optionally, drying the isolated product at suitable temperature.

In embodiments of step a), the solvent may include but not limited to, alcohols such as methanol, isopropanol and the like; ketones such as acetone, methyl isobutyl ketone and the like; ethers such as diethyl ether, tetrahydrofuran and the like; esters such as ethyl acetate, propyl acetate and the like; water; mixture thereof. Preferably solvent is a mixture of alcohol and ketone solvent. More preferably, solvent is a mixture of isopropyl alcohol and acetone.

In one of the embodiments of step a), any physical form of Adagrasib may be utilized, which may be crystalline or amorphous, for providing the suspension of Adagrasib in a solvent comprising betacyclodextrin. In another embodiment of step a), any physical form of Adagrasib may be utilized, which may be anhydrous or hydrate or solvate for providing the suspension of Adagrasib in a solvent comprising betacyclodextrin.
Isolation of crystalline form DRC2 of Adagrasib in step b) may be performed by any technique known in the art. Specifically, crystalline form DRC2 of Adagrasib may be isolated from the mixture of step a) by filtration followed by drying.
The resulting compound obtained in step (b) may optionally be further dried. Drying can be carried out in a tray dryer, vacuum oven, air oven, cone vacuum dryer, rotary vacuum dryer, fluidized bed dryer, spin flash dryer, flash dryer, or the like. The drying can be carried out at temperatures between RT to 75 °C or at a temperature of about 50 °C or any other suitable temperatures; at atmospheric pressure or under a reduced pressure; as long as the Adagrasib is not degraded in its quality. The drying can be carried out for any desired time until the required product quality is achieved. Suitable time for drying can vary from few minutes to several hours for example from about 30 minutes to about 24 or more hours.

Eighth, aspect, the present application provides a pharmaceutical composition comprising crystalline form DRC2 of Adagrasib and at least one pharmaceutically acceptable carrier.

Ninth aspect of the present application relates to crystalline form DRC3 of Adagrasib characterized by one or more peaks selected from its powder X-ray diffraction (PXRD) pattern having peaks at about 3.7, 7.1, 8.6, 9.2, 10.1, 10.9, 11.3, 12.1, 12.7, 13.1, 13.8, 14.2, 14.8, 15.1, 15.6, 16.7, 17.1, 17.4, 17.8, 18.6, 19.1, 19.4, 20.2, 20.5, 20.9, 21.6, 22.0, 22.3, 22.8, 23.2, 23.6, 24.2, 25.1, 25.4, 26.2, 26.8, 27.9, 28.2, 29.0, 30.3, 30.8, 32.1, 32.9, 33.4, 33.9, 34.7, 35.8, 37.6, 38.9 ± 0.2° 2?.

Tenth aspect of the present application relates to crystalline form DRC3 of Adagrasib characterized by a PXRD pattern substantially as illustrated in Figure 3.

Eleventh aspect of the present application relates to a process for preparing crystalline form DRC3 of Adagrasib; the process comprising;
a) providing a slurry or a suspension comprising Adagrasib and pamoic acid by mixing Adagrasib with pamoic acid in presence of a solvent;
b) isolating crystalline form DRC3 of Adagrasib from the mixture of step a); and;
c) optionally, drying the isolated product at suitable temperature.

In embodiments of step a), the solvent may include but not limited to, alcohols such as methanol, isopropanol and the like; ketones such as acetone, methyl isobutyl ketone and the like; ethers such as diethyl ether, tetrahydrofuran and the like; esters such as ethyl acetate, propyl acetate and the like; water; mixture thereof. Preferably, solvent is an alcohol solvent. More preferably, solvent is methanol.
In one of the embodiments of step a), any physical form of Adagrasib may be utilized, which may be crystalline or amorphous, for providing the suspension of Adagrasib in a solvent comprising pamoic acid. In another embodiment of step a), any physical form of Adagrasib may be utilized, which may be anhydrous or hydrate or solvate for providing the suspension of Adagrasib in a solvent comprising pamoic acid.

Isolation of crystalline form DRC3 of Adagrasib in step b) may be performed by any technique known in the art. Specifically, crystalline form DRC3 of Adagrasib may be isolated from the mixture of step a) by filtration followed by drying.
The resulting compound obtained in step (c) may optionally be further dried. Drying can be carried out in a tray dryer, vacuum oven, air oven, cone vacuum dryer, rotary vacuum dryer, fluidized bed dryer, spin flash dryer, flash dryer, or the like. The drying can be carried out at temperatures between RT to 75 °C or at a temperature of about 50 °C or any other suitable temperatures; at atmospheric pressure or under a reduced pressure; as long as the Adagrasib is not degraded in its quality. The drying can be carried out for any desired time until the required product quality is achieved. Suitable time for drying can vary from few minutes to several hours for example from about 30 minutes to about 24 or more hours

Twelfth, aspect, the present application provides a pharmaceutical composition comprising crystalline form DRC3 of Adagrasib and at least one pharmaceutically acceptable carrier.

In an aspect of the present application the crystalline forms DRC1 and/or DRC2 and/or DRC3 of Adagrasib may optionally be subjected to a particle size reduction procedure to produce desired particle sizes and distributions. Milling or micronization may be performed before drying, or after the completion of drying of crystalline form DRC1 and/or DRC2 and/or DRC3 of Adagrasib. Equipment that may be used for particle size reduction includes but not limited to ball mill, roller mill, hammer mill, and jet mill.
The crystalline forms DRC1 and/or DRC2 and/or DRC3 of Adagrasib of the present application is stable and has excellent physico-chemical properties. The crystalline form DRC1 and/or DRC2 and/or DRC3 of Adagrasib of the present application may be easily formulated into a pharmaceutical composition comprising Adagrasib.
Yet another aspect of the present application relates to a pharmaceutical composition comprising crystalline forms DRC1 and/or DRC2 and/or DRC3 of Adagrasib and one or more pharmaceutically acceptable excipient. Crystalline form DRC1 and/or DRC2 and/or DRC3 of Adagrasib with one or more pharmaceutically acceptable excipients of the present application may be formulated as: solid oral dosage forms such as, but not limited to, powders, granules, pellets, tablets, and capsules; liquid oral dosage forms such as, but not limited to, syrups, suspensions, dispersions, and emulsions; and injectable preparations such as, but not limited to, solutions, dispersions, and freeze dried compositions. Formulations may be in the forms of immediate release, delayed release, or modified release. Further, immediate release compositions may be conventional, dispersible, chewable, mouth dissolving, or flash melt preparations, and modified release compositions that may comprise hydrophilic or hydrophobic, or combinations of hydrophilic and hydrophobic, release rate controlling substances to form matrix or reservoir or combination of matrix and reservoir systems. The compositions may be prepared using any one or more of techniques such as direct blending, dry granulation, wet granulation, and extrusion and spheronization. Compositions may be presented as uncoated, film coated, sugar coated, powder coated, enteric coated, and modified release coated.
Pharmaceutically acceptable excipients that are useful in the present application include, but are not limited to: diluents such as starches, pregelatinized starches, lactose, powdered celluloses, microcrystalline celluloses, dicalcium phosphate, tricalcium phosphate, mannitol, sorbitol, sugar, and the like; binders such as acacia, guar gum, tragacanth, gelatin, polyvinylpyrrolidones, hydroxypropyl celluloses, hydroxypropyl methyl celluloses, pregelatinized starches, and the like; disintegrants such as starches, sodium starch glycolate, pregelatinized starches, crospovidones, croscarmellose sodium, colloidal silicon dioxide, and the like; lubricants such as stearic acid, magnesium stearate, zinc stearate, and the like; glidants such as colloidal silicon dioxide and the like; solubility or wetting enhancers such as anionic, cationic, or neutral surfactants; complex forming agents such as various grades of cyclodextrins and resins; and release rate controlling agents such as hydroxypropyl celluloses, hydroxymethyl celluloses, hydroxypropyl methylcelluloses, ethylcelluloses, methylcelluloses, various grades of methyl methacrylates, waxes, and the like. Other pharmaceutically acceptable excipients that are useful include, but are not limited to, film formers, plasticizers, colorants, flavoring agents, sweeteners, viscosity enhancers, preservatives, antioxidants, and the like.
X-ray powder diffractograms of crystalline forms DRC1 and/or DRC2 and/or DRC3 of Adagrasib is recorded on PANalytical X-ray diffractometer, Model: panalytical empyrean. System description: CuK-Alpha 1 wavelength=1.5405980 Å, voltage 45 kV, current 40 mA. The diffractograms were collected over a 2? range of 3-40 °.

DEFINITIONS
The following definitions are used in connection with the present application unless the context indicates otherwise.
The terms "about," "general, ‘generally," and the like are to be construed as modifying a term or value such that it is not an absolute. Such terms will be defined by the circumstances and the terms that they modify as those terms are understood by those of skill in the art. This includes, at very least, the degree of expected experimental error, technique error and instrument error for a given technique used to measure a value.
A name used herein to characterize a crystalline form should not be considered limiting with respect to any other substance possessing similar or identical physical and chemical characteristics, but rather it should be understood that these designations are mere identifiers that should be interpreted according to the characterization information also presented herein.
All percentages and ratios used herein are by weight of the total composition and all measurements made are at about 25°C and about atmospheric pressure, unless otherwise designated. All temperatures are in degrees Celsius unless specified otherwise. As used herein, the terms “comprising” and “comprises” mean the elements recited, or their equivalents in structure or function, plus any other element or elements which are not recited. The terms “having” and “including” are also to be construed as open ended. All ranges recited herein include the endpoints, including those that recite a range between two values. Whether so indicated or not, all values recited herein are approximate as defined by the circumstances, including the degree of expected experimental error, technique error, and instrument error for a given technique used to measure a value.
The term “optional” or “optionally” is taken to mean that the event or circumstance described in the specification may or may not occur, and that the description includes instances where the event occurs and instances where it does not.
In general, a diffraction angle (2?) in powder X-ray diffractometry may have an error in the range of ± 0.2o. Therefore, the aforementioned diffraction angle values should be understood as including values in the range of about ± 0.2o. Accordingly, the present application includes not only crystals whose peak diffraction angles in powder X-ray diffractometry completely coincide with each other, but also crystals whose peak diffraction angles coincide with each other with an error of about ± 0.2o. Therefore, in the present specification, the phrase "having a diffraction peak at a diffraction angle (2?±0.2º) of 19.6º" means "having a diffraction peak at a diffraction angle (2?) of 19.4º to 19.8º. Although the intensities of peaks in the x-ray powder diffraction patterns of different batches of a compound may vary slightly, the peaks and the peak locations are characteristic for a specific polymorphic form. The relative intensities of the XRD peaks can vary depending on the sample preparation technique, crystal size distribution, various filters used, the sample mounting procedure, and the particular instrument employed. Moreover, instrument variation and other factors can affect the 2-theta values.
Certain specific aspects and embodiments of the present application will be explained in greater detail with reference to the following examples, which are provided only for purposes of illustration and should not be construed as limiting the scope of the disclosure in any manner.

EXAMPLES
Example-1: Preparation of crystalline form DRC1 of Adagrasib
A mixture of Adagrasib (0.5 g) and Aspartame (0.5 g) in isopropyl alcohol (2.5 mL) and acetone (2.5 mL) was stirred for 39 days at room temperature. The resulting mixture was filtered and dried under VTD dryer for 2 days at 35 °C to obtain the title compound. PXRD pattern is shown in Figure 1.

Example-2: Preparation of crystalline form DRC2 of Adagrasib
A mixture of Adagrasib (0.5 g) and betacyclodextrin (0.5 g) in isopropyl alcohol (2.5 mL) and acetone (2.5 mL) was stirred for 39 days at room temperature. The resulting mixture was filtered and dried under VTD dryer for 2 days at 35 °C to obtain the title compound. PXRD pattern is shown in Figure 2.

Example-3: Preparation of crystalline form DRC3 of Adagrasib
A mixture of Adagrasib (0.4 g) and pamoic acid (0.04 g) in methanol (0.5 mL) was stirred for 25 days at room temperature. The resulting mixture was filtered and dried under vacuum for 2 days at 35 °C to obtain the title compound. PXRD pattern is shown in Figure 3.
,CLAIMS:We Claim:
1. Crystalline form DRC1 of Adagrasib characterized by one or more peaks selected from its powder X-ray diffraction (PXRD) pattern having peaks at about 6.5, 8.6, 11.2, 12.9, 14.6, 16.0, 16.7, 16.9, 17.9, 18.1, 19.9, 20.1, 21.2, 21.5, 22.9, 23.5, 24.1, 24.5, 24.8, 25.4, 26.2, 26.6, 27.3, 27.9, 28.5, 29.0, 30.4, 31.3, 31.7, 31.9, 32.6, 33.5, 34.0, 34.5, 34.9, 35.3, 37.1, 37.8, 39.5 ± 0.2 2? [or] characterized by a PXRD pattern substantially as illustrated in Figure 1.
2. A process for preparing crystalline form DRC1 of Adagrasib; the process comprising;
a) providing a slurry or suspension comprising Adagrasib and Aspartame by mixing Adagrasib with Aspartame in presence of a solvent;
b) isolating crystalline form DRC1 of Adagrasib from the mixture of step a); and;
c) optionally, drying the isolated product at suitable temperature.

3. Crystalline form DRC2 of Adagrasib characterized by one or more peaks selected from its powder X-ray diffraction (PXRD) pattern having peaks at about 5.0, 6.4, 6.9, 8.2, 9.2, 10.0, 10.3, 10.6, 12.1, 12.3, 13.2, 13.6, 14.1, 14.3, 14.7, 15.3, 16.1, 16.4, 16.7, 17.3, 17.9, 18.3, 18.5, 19.5, 19.9, 20.2, 21.1, 21.3, 21.6, 22.4, 22.6, 23.6, 23.9, 24.9, 25.7, 25.9, 26.3, 27.1, 27.8, 28.5, 29.1, 30.3, 31.4, 32.5, 33.6, 34.5, 35.4, 37.6, 37.9, 39.2 ± 0.2° 2? [or] characterized by a PXRD pattern substantially as illustrated in Figure 2.

4. A process for preparing crystalline form DRC2 of Adagrasib; the process comprising;
a) providing a slurry or a suspension comprising Adagrasib and ß-Cyclodextrin by mixing Adagrasib with ß-Cyclodextrin in presence of a solvent;
b) isolating crystalline form DRC2 of Adagrasib from the mixture of step a); and;
c) optionally, drying the isolated product at suitable temperature.

5. Crystalline form DRC3 of Adagrasib characterized by one or more peaks selected from its powder X-ray diffraction (PXRD) pattern having peaks at about 3.7, 7.1, 8.6, 9.2, 10.1, 10.9, 11.3, 12.1, 12.7, 13.1, 13.8, 14.2, 14.8, 15.1, 15.6, 16.7, 17.1, 17.4, 17.8, 18.6, 19.1, 19.4, 20.2, 20.5, 20.9, 21.6, 22.0, 22.3, 22.8, 23.2, 23.6, 24.2, 25.1, 25.4, 26.2, 26.8, 27.9, 28.2, 29.0, 30.3, 30.8, 32.1, 32.9, 33.4, 33.9, 34.7, 35.8, 37.6, 38.9 ± 0.2° 2? [or] characterized by a PXRD pattern substantially as illustrated in Figure 3.

6. A process for preparing crystalline form DRC3 of Adagrasib; the process comprising;
a) providing a slurry or a suspension comprising Adagrasib and pamoic acid by mixing Adagrasib with pamoic acid optionally in presence of a solvent;
b) isolating crystalline form DRC3 of Adagrasib from the mixture of step a); and;
c) optionally, drying the isolated product at suitable temperature.

7. Suitable solvent as claimed in claim 2) and 4) is a mixture of alcohol solvent selected from and ketone solvent.

8. Suitable as claimed in claim 7) is a mixture of isopropyl alcohol and acetone.

9. Suitable solvent as claimed in claim 6) is an alcohol solvent selected from a group comprising methanol, ethanol, isopropyl alcohol.

10. A pharmaceutical composition comprising crystalline form DRC3 and/or crystalline form DRC3 and/or crystalline form DRC3 of Adagrasib and at least one pharmaceutically acceptable carrier.